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Update to Literature Search No. 394 Toxicity and Pyrolysis of Propylene Glycol

Date: 27 Sep 1985
Length: 182 pages
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September 27, 11985: UPDATE TO LITERATURE ~ SEARCH NO., 394, TOX'ICITY' AND PYP!OLYSI'S OF PROPYLENE GLYCOL Requested by Elizabeth Wagner
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Search Terms: pt-oo•;.1 ene gil •;;ri3,l 1 ~:`-propanedi o1 SOUE:CES I hJ E'Fi I IVT 1981 Chemical Sources Assn. FLAVOR & FRAGRANCE I'1ATEF:IALS,.' Sept. 1985 Cammerce Clearing House. FOOD DRUG COSMETIC LAW REPORTER. 1975 Gossel i n. CL I1V I CA'L TOX I f,'OLOGY OF COM'MEf;C IAL F'F;ODUCTS'. 1981 HEath. SOURCEBOOf`".. OF FLA'./OF.'S'.. 1984 li;irk-Othmer. ENCYCLO1='EDIA,OF CHEMICAL TECHNOLOGY. 1983 t"tEE.FtCt=:: I IVI7E X ., 1979 ' O'pdyE:e. MONOGRAPHS ON FFtAGF:AIVCE RAW' MATERIALS. 11982 Clayton. F'ATTY'S INDUSTRIAL HYGIENE AND TOXICOLOGY. 1984 . Sa.:. DAhIGEROUS~ F'f!;OF'EFtTIES OF INDUSTRIAL MATERIALS. v. ^Es-u. 2° 1982L.-19f34 TOBACCO AEiST""ACTS.
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S(DUFtCES~ ONLINE BRS O5: iis~?' F;azar-c,l in_. ('H%rF;)1 CAS ONLINE (updated thr-ough vol. 107. ' issuE' '..iir, 1955) NATIONAL LIBRARy' CIE MEDIOINE Update Avl. Ei l'e e509 (EM) ELHILL. TOXLINE S5'09(EM); ELHIIIL. C'ANCERLIT e506 (EM) ELHILL. RTErS. 850528 TClnNET. HSDB/Tl.~:Es (revi si on date) D'I ALOS FILE Uf'D'ATE NAME 1.1SI 195:' Chemical E::posure 174Nov 8 : Chemical Regulations and Suide,lines 2'6E Mar 85 f=ederal' Re..search In ProgrEss. 51' Oct SS Foodl Science And' Tiechnology Abstracts 79' Auq 85 Foods Adlibra 161 Apr 85 h:?ational Institute for OccuPationai Safety and Heal ttr
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.t RN 57-55-6 M 1,2-Fropanedzol (SCL, 9CI) SY PG 12 SY, 1,2-Dihydhoxypropane SY Methylethylene glycol , SY Monopropylene glycol SY Propylene glycol - SY' .aipha,.-Fropylene glycol SY 1,2-?ropylene gaycol' SY' Sirlene SV' 2',ti-Propanedibl SY Mpthylethyl glycoli SY ^c-Hydroxypropanol. SY Isopropyl'ene glycol. SY Solar Winter Ban SY Ucar 35 SY Solargard F' SY Dowfrost. DF' 63625-56-9 MF C3 H8 02 CI COM, TSCA HOCH2CH(OH)Me REFERENCES INI FILE CAOLD (PRIOR TO 1967')' 4217 FEFEtRENCES'IN FILE CAi(1967 TO DATEY ANS I 6
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_ - _ R- T F, , Y 0 F T OX' I C E F F E C T S a. OF CL-iEMliC,1-*-%4L, SUBSTAfi!CES m ~ N'ATIONAL LIBRARY O!1F. M!ED1CINE ~ SPECIALIZED INFORMATION SERVICES ~~ TOXICOLOGY INFORMATION PROGRAM
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RTEC'5. C INTRODUCTI ON I!n September 1977, NLhil i added the 1976' edition of' the data retrievall file known as the Registry of Toxic Effects of'Chemica9 Substances (RTECS)1o its family of'online services. RTECS i's structuredaround individuaf chemical record5 of' substances with toxic action: The: originaF collection of'data that makes upp the Registn+ of'Toxic Ef`ects of Chemicai!Substances was known, as the Toxic Substances List.,compil6el in 1971 by the National Institute tor Occupationat Safety and Health (NIOSH)', in rtesponse to the Occupational Safety and Health Act of' 1970s The hardI copy, version, of' RTECS is updated annually, withi quarterly microfiche editions available. The current ONLi'NE version isibased; on the 1979 printed editaonpius quarterly updates. It contains toxicity data for approximately: 53s 000: substances (4/82):. RTECS is a single source document; for baslc:toxicity Information. RTECS Includes toxicity data from a variety: of'printed: sources, threshold limit values, aquatic toxiicity ratings, air standards, NCI carcinogenic bioassay information, toxicological/carcinogenic review information4 compound', ciassificaroion, and NIOSH Criterion Document availabilty. It is especially usefui for retrieving inforrnation, on a group of compounds or identifying a group of'substances on the basis of'ai seiected effect orcr'iterion.Oniine RTECS gives the user the flexibility of interactive searching and: retrieval which can aiiow focus on subsets of data aW data taiiored'to specific needs:. The telephone number for questions on the system„communication problems, program interpretation, etc., is (301), 496-6193 or (800) 638-8'480, (tolll fhee): The; telephone number for technical assistance in, RTECS search strategy, etc., is (301) 496-1i13'1'..
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RTECS UNIT RECORD PRINT OPTIONS SEARCH PRINT S F T D MNEM.. DATA ELEMENT MNEM. D U D L (Siy (N1) CHEMICAL IDENTIFICATION DATA: Secondary Source IDi CAS Type 1 Name, Si' Ni X' X (SY) (NF) (RN) (CC), (MF), (FF), Synonyms Narne Fragments CAS Registry Number CI'assificati'on Code Molecular Formula Formula Fnagments Molecular Weight SY RN' X CC~ MF MW'- X - X - X X X X. (WL) Wiswesser Line Notation WL - - - X' (EM) Entry Month EM - - - X (17C) 'TOXICITY' DATA AND! SOURCES: Toxicity, Data Index Sthing, TDiCWN' - X X ' X (CWIn; Toxic Data Source SOl - X X X STiANDARDS„ REGULATIONS,, AND ADDITIONAL TOXICOLOGICAL DATA: (TW) Chemical Definition, CDEF - - - X. (TW) Aquatic Toxicity Rating i A.O - X - X' (T1d41) Toxicology & Cancer Rewiew TR - X - X )l Standards & Regulations S'RI - X - X ' (TW) N10SH' Crirteria Documents NC' - X - 7K' (TW) Status ST - X , - X ' •Note, only the hit sources and/or their associated'I index strings p.nt: unless "COMPLETE" Is added to the following print commande, "PRT FU"', "PRT DL", "PRT TD'", "PRT TDi<WV"; and' "PRT SO".
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R7~tes SECONDARY SOURCE ID NIOSH/TY2000000 CAS TYPE 1' NAME 1,2-PROPANEDIOL CAS:REGISTRY NUMBER 57-55-6 CLASSIFICATION CODE AGRICULTURAL CHEMICAL, CLASSIFI!CATION CODE MUTATION DATA CLASSIFICATION CODE REPRODUCTIVE DATA CLASSIFICATION CODE PRIMARY IRRITANT CLASSIiFiCATION CODE GERMICIDE TOXICOLOGYZCANCER',REVSEW TOXICOLOGY REVIEW AJMEAZ' STATUS STATUS STATUS STATUS SYNONYMS'. SYNONYMS: SYNONYMS SYNONYMS SYNONYMS SYNONYMS SYNONYMS. SYNONYMS SYNONYMS SYNONYMS SYNONYMS, SYNONYMS SYNONYMS SYNONYMS MOLECULAR FORMULA MOLECULARWEIGHT WISWESSER LINE NOTATION ENTRY MONTH TOXIC DATA,SOURCE', TIOXDATA KEYWORDS TOXIC DATA SOURCE', TOXDATA KEYWORDS TOXIC DATA SOURCE Medicine. 38,409,65 American Journal of REPORTED INI EPA TSCA INVENTORY, 1983 EPA GENETIC TOXICOLOGY PROGRAM, JANUARY 11984 EPA TSCA SECT ION! 8(1e ) STATUS' REPORT 8EHG1+-0178'-00411 MEETS CRIiTER'I'A FOR PROPOSED RECORDS RULE 47,30420,82; 1,2-DIHYDROXYPROPANE DOWFROST METHYLETHYLENE GLYCOL METHYL,GLLYCOL MONOPROPYLENE GLYCOL PG 112 PROPANE-1i,2'-DI'OL PROPYLENE GLYCOL PROPYLENE GLYCOL USP' al'pha-PROPYLENEGLYCOL. 1,2-PROPYLENE GLYCOL SIRLENE SOLAR' WINTER F3AN1 TRIMETHYL GLYCOL C3-H8-O2 76.111 . QY1&iQl 8506 JIDEAE Journal 55,19+J,70 of OSHA' MEDICAL FEREAC Iinvesti,gative Dermatol'ogy. Sk!:I',N;HUMAN;IHUMANS; IIFiRITATION; 500 mg/7D g TiOXIC EFFECTS;MILD B:.DYAB:"Cutaneous Tioxicity,," V.A. Drilil and P. Lazar, eds. , New, Yor1::,, Academic Press, 1977 -;,1<7,77' SN•'.IN;HUMAN;HUMANS;,IRRITATION;1U4 mg/3D-I (y~} TOXIiC EFFECTS;MODERATE ~. JIDEAE Journal of Investigative Dermatol,ogy., ~, 19,,4231,52 TOXDATiA KEYWORDS SF:INk'MAN,HUMANS; IRRITATIONi,1cJV./2D ~I TOXIC DATA,SOU[tCE' FCTOD7 Food and Chemical Toxicolocoy. ~ 20,573,B2 ~y TOXDATA KEYWORDS EYE;RA$$IT;,RODENTS;IF:RITiATIDN;j1Coq mg ;TOXIC: Q EFFECT.S;,MILD
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TiOXIC DATA SOURCE 2BZPAK "Sbornik Vysledku Toxixologickeho Vysetreni Latek A Pripravk.u," J.V. Marhold', Institut Pro VKchovuiVedoucicn Pracovniku Chemickeho P'rumycl'u Praha, Czechoslovakia, 1972 -,37,,72 TOXDATA KEYWORDS TOXIC DATA SOURCE TOXDATA' KEYWORD& OXIC DATA SOURCE TOXDATA KEYWORDS', TOXIC DATA'SOURCE EYE;RABBTT;;RODENTS;IIRRITATION;5p0 mg/24H TOXMEFFECTS~MODERATE APMUAN:Acta Pathologica et Microbiologica Scandinavi'ca, Supplementum. 5274,3!44,81 MUTATI1ON;DNA' I'NHIBITIAN;'MOUSE;RODENTS' SUBCUTANEOUS;8GO0 mg/kg MUTATION;CYTO(3ENETIiCSqMOUSE';RODENTSI SUBCUTANEOUS;8G0© mg/kg )r FCTOD7 ~Food Wand:uGhemiical , Tox i col ogy. ar22`;623'£~~4'M* MUTATION;',CYTOGENETICS;HAMSTER;,RODENTS FIBROBLAST;,SOMATIC CELLS;,32 gm/L KAIZANI Kaibogaku,Zasshi. Journali of Anatomy. 37,239,62 TOXDATA KEYWORM OXIC DATA SOURCE. TOXDATA KfYWORDSI TOXIC DATA SOURCE: INTRAPERIiTONEAL;M(7USE;RODENTS;',TDLo; 100 mg/Icq (1'1D preg)I;'TOXIC'EFFECTS;REPRODUCTIVE FERTiI L ITY I'NTRAPERITONEAL; MOUSE; RODENTS; TDLo;,1U0 mg /k:g (15D preg);TOXIC EFFECTS;:REPRODUCTIVE' EMBRYOTOXICITY' JOPDAB' Journali of Pediatricss 93,515,78 ORALi;,CHILD;,HUMANS;TDLo;,79 gm/kg/56W-I; TOXIC', EFFECTS;:CENTRAL NERVOUS S1"STEM;BEHAVIORAL SYMPTOMS;'CONVULSIiONS TX'APA9'Toxicology and!Applied Pharmacology. 45,:362', 78 TOXDATA KEYWORDS TOXIC DATA SOURCE TOXDATA k.EYWORDS TOXIC DATA SOURCE' TOXDATA KEYWORDS TOXIC DATA SOURCE . ORAL;RAT; RODENTS; LD50;,2GG gm/kg KRKRDT Kriobiologiya i Kri'omeditsina. 9,36,81 INTRAPER''ITONEAL;RAT;;RODENTS;LD5U;,6660 mg/k.g, TOXIC EFFECTS; JLHTA& Journal ofl Industrial Hygiene and Toxicology. 3:1,256,49 SUBCUTANEOUS;RAT;RODENTS;,LDS0;28 gm/kg NTIS** NationaS TechnicaT Iin~Formation Service, PB2BC1-477 ~ TOXDATA KEYWORDS INTRAVENOUS;~RAT;iRODENTS;LLD 50;6aOO' mg/kp ~ TOXIC DATA SOURCE' TOXDATA KEYWORDS TOXIC DATA SOURCE', TOXDATA KEYWORDS TOXIC:DATA,SOURCE JIHTAB,Journal of Industrial Hygiene,a.nd Toxicology. =1,256,49 INTi";AMUSCULAR;.RAT; RODEIWTS;LD5tj;;2.u gm/kg IPA JPHTAB Journal ofl Industrial Hygiene and N Toxi'cology. 21,,173,39. OF:AL;MOUSE;,RODENTS;,LD50;24 gm/kg FEPRA7 Federation Proceedings, Federation of American Societies for Experimental Biology. 6,342,47 TOXDATA KEYWORDS TOXIC DATAiSOURCE INTRAPERITONEAL;MOUSE!;RODENTS;;LD5V;971'8'mg/kg TOXIC EFFECTS;PULMONARY SYSTIEMtUROCENQTAL SYSTEM;SLOOD k:Rk:RDT N:riobiol'ogiya i k::rior:reditsi,na. 8,46,81
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TOXDATiA KEYWORDS TOXIC DATfi'SOURCE TOXDATA KEYWORDS TOXIC DATA'SOURCE TOXDATA KEYWORDS TOXIC DATA SOURCE TOXDATA KEYWORDS TOX'IC DATA SOURCE TOXDATA KEYWORDS TOXIC DATA SOURCE TOXDATA KEYWORDS TOXIC~DATA SOURCE SUSCUTiANEOUS;,MOUSE;~RODENTS;L'D50;1737U mg/kg TOXI!C EFFECTS;PEHAVI'ORAL SYMPTOMS;PULMONARY SYSTEM J!PETAB J'ournal, of Pharmacology & Experimental Therapeutics. 65y89,39 I'NTRAVENOUS;MOUSE;RODENTS;LD5U;84qG mg/kg JIHTAB Journal of I~ndustrial! Hygiene and Toxicology. 21!,173,39, ORAL;DOG;DOGS;,LDSG;22'gm/kg NTTS** Natibnal Technical Informati'on, Service. FB282-477 INTRAVENOUS; DOG; DOGS;LD.°rGi 26 gm/kg ORAL;RABFIT;,RODENTS;LDLo;:2G gm/kg NPIRI* Raw Material Data Handbook „ V.1 Organic Solvents, 1974. 19,1011,74 SKINSRABB'IT;,RODENTS;!LD5U;2D8UO mg/kg JPETAB'Journal of' Pharmacology & ExperimentaL. Therapeutics. 44,1'f19,32' INTRAVENOUS;RABH:IT;RODENTS;LDLo;4200mg/kg INTRAMUSCULAR;RABB'IT;RODENTS;,LDLo;63C1Q'mg/kg JIHTAB Journal of''. Industrial Hygiene and Toxico110gy., 21,;173,,39' TOXDATA KEYWORDS TOXIC DATAiSOURCE 'L ORAL;GUI!NEAPIG;,RODENTS;:LDSU;!19 gm/kg NTIS** National Technical Information d..Service. PH28Ch-477 TOXDATA KEYWORDS TOXIC DATA SOURCE TOXDATA KEYWORDS SUBCUTANEOUS;GUINEAPIG;RODENTS;LDLo;'15;,00 mg!/kg JPETAB Journal„of Pharmacology & Experimental, Therapeutiics. 6C2,'12,s7 INT'RAIJENOUS; CHICKEN;,&,I'RDS; LDLo; 27 gm/k.g
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NLMiTECHN!tCAL BULLETIN - MAY 85 TOJ(tVET: THE NEW' NLMI TOD(ICOLOGY DATA NETWORk. Bruno M. Vfasta, P'hiil~~ip Wexler Special'ized Dnformati'on Serviices, h4LM! The Toxicology Information Program, operated by NLM's Division of Specil'alired: Informa~tiion Se~rvites (S~IS),isreaching the, final stages of implementing two data banks in the broad areas of toxicology, chemistry and hazardous waste information, as the first components of the Library's new' Toxicology Data Network (TOXNET)Aata,retrievali system. One file iis an expanded version,of the Toxicoliogy Data Bank (TDB) currently in ELHILL, and retaii;ns,theTDB name. Thesecondl file,knownias theHaaardousSubstancesDat& Bank(H!SDB~),,i's, & broader, more comprehensive: file initially contaiiniing the entire TD'B' content., Both of these fil'es are maintained on a Data General Eclipse minicomputer and wiil be accessfible to domestic MEDLARSuserson~ theTaXINET system,asofJu-1iy1,,1985. TheTOXfVET system wi'lToperate in parallel with the ELHILL system under MEDLARS. XDB, ~andif5#i6'enTOXNE"f Initiaily, the Library had planned to offer TDB with the CERCLA-related enha~ncementson a,sing;ledatabase~, replacing the original TDB. For vari~ous, reasonsiit was found preferab~lieto offertwo~files, both~to start with information on the, same4,1001 chemicalis. Qnei1s, theMLM-supportedl T0& wi'thi 96, data elements; the, other is~ the, new HSDB, withI44, dataelements., The dataeTiements, (;orfi'eTd's)in both fflesare~ arranged in th~e, following~ ten broad categoriles, ('seeUniit Recordil Descriptions, Figures 1a~nd 2~ on, p~ages10~ and1I )i: ID Substance Idontification MANF Manufacturing/Use Information CPP Chemical and Physi'call Properties SAFE Safety and Handling TOXB Toxici'ty/Biomedical Effects PHCY Phormacology ENEX Environmental Fate/Exposure Potentiali EXSR Exposure Stand!ards andReg l'ations MAM Monitoring and AnalysiisMethods! R!EFS Additional References Data elements within each of these categories may contain one or more occurrences of data or, possibly,no, datai, if none areavail'able~. Users familiar with the ELHILL TDB should note that the TOXNET TDB wiii continue to, focus; upon toxicologicalinfornnataon and maintain a; high deg~reeof~ qualliity control throughi revi~ewbya, committee! of~ experts. Tihei-scopeof 1iSDB includes-and expands -wpon -Ahat ref=the-T-0B'ky~qr*wadi"g -fuii-ler i nformatiom.,primariiiy irr -the areas :-iof -environmental -#ate .an;d exposure, s,tandards -4md -regul~atiions,~rtonitori~ng ~ and analysiis,-and -safety and, handl,ing. Data are extracted not only from the materials on the TDB source liist but also from a variety of other sources, including Government documents and specia,l reports., Thiis, more~ comprehensivefile(iHSDB), wi1!T be scientifically reviewed and edited, but short of the detailed peer review of TD8.
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tl 5 D 6 Un4 reeA 1. IO 'e SUBSTANCE IDEN7IFICATION NSN MSDa MuwOer NAME Sukstance Nace RN CAS Regiitry Nun6er RELT Ielated Tpp Records ST Synony.s NF lblecular Forsula YtN Ylt.esser Line Notation R1EC RTEES NunDer- OHeIN ONMTADS Number SMPN Shipping Naeie/Nurvber STEC Std. Transport'n Nue4er NAIN EPANatardousNastes No. 4. SAFE "SAFETY a 11A/IDLING NA2S ~ Natards Suenury DOTDOTYEe.ryency Guidelines FLAM ! Flaeayble Properties FPOT Fira Potential NFPA NFPA Natard Classlflcatlon FLNT Flaawakld Limits FLPT Flash Point AUTO Auto/gnltlon TesWerature FIRE ! Fire F/ghting Information FIRP F/re Flghttng Procedures INTN Intentlty oFMeat TO;C Tox1c Ca.bustlon Products OFM1 0ther Firefigbting Na><ards EXPL Explosive Lt.1ts 6 Potential MA1R ~ Hazardous Reactions REAC Reaotlv/ttes I Incoupatibillties DCNP Deco.position -- - ----POLT poly.eritation ONA2 Other Noteroous Reactions YRNP • Narein6 Properties ---~-OORT Odor Threshold SEpi Skin, Eye i Rnpiratory Irrttat/ons PRYN • Preeentive Measures COUP Protectir. Eqripnsnt & Clothing OPRN Other Preventive Meatuns- SSL Staklllty/Shelf.life SHTP ShipKnCMethods I Regulations STpG Storagt-Conditioni CLUP Cleanup MethodsDISP Dlspotal Methods RAOL Radiation Linlts a Potential S. T0i6 t• TOXICITT/61ANEDICAL EFFECTS T0K5 Toxlclty Sunwry TXNR Toxlc Naiard Rating PPOT Polsoning Potential AMTR Antidote-6 Eoerqency Treatstent NEDS Medical Surveil lanct ---TOX f To.iclty Excerpts NTOX Nu.tn Toclctty Excerpts NTOX Non-NUmm Toxicity Excerpts TOXY e Toatclty galues NTXg .....Muun Tosicity values NTXY Non-lwMee To.Tclty Yalues ETYr Ecotoiiclty-Yalws S. Toz6 ee TOXICITT/BIDMEDICAL EFFECTS (cont) 6. EISR re EXPOSURE STANDARDS 6 P€GULATIONS NINF Minimum Fatal Dose Level 10LM ' Irnedlately Dangerous to Llfe or Health POPL PHHR r ADE- Populations at Special Risk Pnaracok/netlct Absorption, Dlstrlbutlon ADI AiOI OPL • Acceptable Dally In;alet Allowable Tolerances Gccupatfonal Per+ittible Levels MET6 bHL ACTN TNTC iExecretion MetaOolts./Metabolltet Iiologlcal Helf-Llf. Mechanism of Action Interactions OSHA NREC TLY OOPL 05NA Standards MIDSN Recommendatlons Threshold Limit Value Other OccupatlonalPerasslole Levels 6. PNCT r~ PNARMACOLOGT DREG ~ YSTD Other Standards and Regulations Water Sundards. 610N 6lonecessity ASTO SSTO Atmospheric 3tendards Soli~-Standards_ . TPER WARN 1D10 TOLR MIIOD EMEI •• TherepeuticUses Druy Narnings-- Drug Idlosyncracies Druq Toleranc_a---- M_axler+. Orug Dose ENYIRONMENTAL FATE/EXPOSURE POTENTIAL CERC TSCA RCRA FIFR FDA CERCLA Reportable Quantttles TSCA Requ/renents RCRA Requireants FIFRA Requlrenients FDA Requtre.ents ENYS Environmental Fate/€spo4un SueMxry 9. WDt MONITORING AND ANALYSIS METHODS POLL • RATS ARTS FATE Pollution Sourcet NaturkllyOccurr/ng Sources Artifictal Sources Environmental Fate (Ateosphertc, Terrestrlal, 6 Aquatic) 0 SAMP ALAS CLAS pEFS Sampling Procedures Analytic Procedures tlintcal Laboratory Methods ADDITIONAL REFERENCES ENVT e Environmental Transforwations - 9100 Btode9radatloa - - - ABIO Ab/otic Gegrad.tlon ENTP ' Environmental Transport B10C Atoconcentration ROC Soil Adsorptlon/Moblllty VWS Volatilization fro. Yater/So11 . RPTS DB TEST M1ST Speclal Reports Onn•I1ne Databases Test Status PriorHlstory of Accidents ENYC e Enrlronantal Concentrations YATE stater Concentration EFFL Effluent Concentrations SEOS Sedleent/Soil Concentretlons ATMC AtnosPheric TonuntrationsFOOD Food-Survey Yelues - PLOT Plant Concentrattons FISH Fl F l Prepared by- BFIB/SIS sh/SN ood Concentrat ons ANML Animal Concentrations July 1985 NILK Mtlt Concentrations OEYC Other Environnentel Concentrations MUEI • MuNn Exposure RTEX Probable Routes of Human Eeposure AYDI Aterage Daily Intake - P6E1 Probable Exposures lODT 6ody faurden 2. MANF !- MANUFACTURING/USE INFORMATION M}FG Methods of Manufacturing IMP Impurities FORM_ Fora4Uons/Preparatlons MFS Manufacturers BMIM Other Manufecturtng Information USE Major Uses CPAT Consumption Patterns RRDD U.S. Productfon IMRT U.S. leqorts EXRT U.S. E.ports ). CPR CHEMICAL a PHYSICAL PROPERTIES COFO ColorlForw ODOR Odor TAST Taste BP Boiling Point nP tklttng/Freettng Point Nw HoleculerHeiqh_t ----- CORR Corrosleity-~ - CTP- Criticel-Teenerature 6 Pressure DEN Denfltr/SRecif/c Gravity DSC Disioclation Constants NTC Neat of Co.bustlon MTt Naat of Yaporitation OUPC OcLanolFUater Partition Coeff. PH pM SOL Soluollitles SPEC Spectral Properties SURF Surface Tentlon VAPO Vapor penslty YAp Vapor Presiure EYAP Relatlre Evaporation Rate YISC Mtscoslty - OCPP Other Che.lcal/Physical Prop. Fieure.l_----- Vi-4 TV KA.cd
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HAZARDOUS SUS'STANCES DATABANF?:: NUMBER 'L;S:T FIEY ISI OI'4 DATE 1R. ECOR D, {:._ENG TH NAME OF SUDSTANCE CAS' F;EG,I STI'-,iY NUMBER SYNONYMS SYNONYMS SYNONYMS SYNONYMS SYNONYMS SYNONYM'S. SYNONYMS SYNONYMS SYNONYMS. SYNONYMS' SYNONYMS SYNONYMS SYNONYMS SYNONYMS MOLECULAR FORMULA WISWESSEF; LINE NOTATION RTECS NUMEER' OF+IM-T ADS NUMBER METHODS OF P'tANUFACTUR IN.f6 MANUFACTURERS MANUFACTURERS MANUFACTURERS MANUFACTURERSMANUFACTUR'ERS' MAtVUFACTURERS MAJOR USES CONSUh'IF'T I ON F'ATTEFiNS UL S. FfiODUCTION! . U'. S. PF;ODUCT'IiON' U. S. IMPORTS U. S. aMPORTS U.'S. E?(P OR TS U. S. EXrOnTS 174 ..C' C,... ~O3J~ ~.i~ 1 3 "-'c'1 PROPYLENE GLYCOL 57-55'-6 1 , i-D I HYDROXYF`ROF'A'NE' 1 , 2-F'FkOF'ANEDI OL 1 , 2--F'ROf-'YLENE GLYCOL C,''-FROF'ANEDIOL '?-HYDROXYF'ROO FANOL ALPHA-PROPYLENE GLYCOL METHYL GLYCOL METHYLETHYL GLYCOL METHYLETHYLENE'GLYCOL MONOF'ROF'YLENE GLYCOL. F' G 1 *2 F'ROF'ANE-1',: -DIOL SIRLENE TFtIMETHYL GLYCOL C_-H3-0^ QY1 0 N I OSH'/ TY2c]0cat'jcaij 7'2'16877 HYDRATION OF PROPYLENE OXIDE [SRI] CELANESE' CORP, CELANESE CHEM CO, D'IV'', BISHOP, TEX: QSRI] DOW CHEM USA , FF;EEF'ORT', TEX, F'LAQUEM I NE ,, LA [SE:I ]'. JEFFERSON E'F-{EM CO',, IN'C~, F°OR'T' NECHES, TEX'. [SRI] OLINCORP, DESIGNED F'RODWCTS DiW, DRANDENBURG', F;::Y G S;Fi`.I ] OX IFtiANE CHEM CO, BAYPORT, TEX ESF;'I ] UN I ONl CAREi I'JE COF':F', CHEM'S' AND PLAST'I CS D'I u, INSTITUTE AND SOUTH CHARLESTON, W VA [SRI] CHEMICAL INTERMEDI~ATEI'NSYNTH 0'FF'OLYESTERF;ESIN&; COMMODITY FOF~t EXPORT; COMF'ONE~NTOF CELLOPHANE [SRI ]'. 52% ' FOR F'OLYESTER F'ES TNS, 1 1% EX'F'La :TED (1'97-')~; 5.5% FOR CELLOPHANE; 7. 5'/. AS. A TOBACCO HUMECTANT; 7% FORSYNTF:-IESISOF F'OLYME.RI C F'I_AST :[ C I ZEF"S ; 4% AS A Crh11PONENT OF BRAk::E AND OTHER FUNCTIONAL FLU'IDS; 10'/. FOR t•I I',SC AF"`L I CAT I ON""' (1.'7:_: ) E OFi I] ( 1 972") 2_60X1t;+11 GRAMS [Sf;I ]' (1975) T . 77)€'i:()F11'. G{'•-.'AM31 [SF:I ] ~ ( 1'.97L') ND GSFtI ] (1975) ND CSf;'I] (1972) 4.90X1Q%'_1'c~:j rRAMS CSFtIJ (1''i7fi) :'., IlXlt`_;+1i~ Gfni=1'Mta LSF.I] C!T
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,E;LOR /FOFt?`1 -_inrli-i' TASTE BOILING POINT MOLECULAR WEIGHT DENSITY/SPECIFIC GRAV'ITY HEAT OF COMEiU,-t3T I ONI HEAT OF V'APOf:I ZAT I ON S'OLUBIL.ITIES SF'ECTRAL PROPERTIE& SURFACE TENSION VAPOR PRESSURE VI SCL S I TY OTHER CHEM.ICAL/PHYSICAL PROPERT DES! OTHER CHEMICAL/PHYSICAL PROPERTIES OTHER CHEMICAL/PHYSICAL PROPEF:T IES OTHER CHEhi I CAL/PHYSI CAL PROPERTIES FI!R'E POTENTIAL FLASH POINT AUTO i GN,I T I(7N TEMPERATURE FIRE FIGHTING F'fiOCEDURES EXPLOSIVE LIMITS AND PO T ENT:[ AL COLORLESS VISCOUS L I nU I D C HAWLEY. CONDENSED CHEM D I CThtF-;''( 9TH ED 119773 F'RA'CT ICALLY O7ORLEC: S[ HAWLEY. CONDENSED CHEM DICTb:1RY 9TH ED 197771 PRACTICALLY TASTELESS [HAWLEY. CONDENSED CHEM DICTN'Fi'f 9TH ED11977] 189 DEG C[WEAST., HDBK CHEM' & PHYS 60TH ED 19791 76.11 [1rJEAST. HDBK CHEM & PHYS 6(-.)TH ED, 119791 1. C7•_61 @ '20 DEG C/4 DEG C[WEAST. HDBK CHEM, & PIHYS 60TH ED 19797 431.0 KG CAL/MOLE CHA'WLEY. CONDENSED CHEM DICTNRY 9TH ED 119773 168.6 CAL / G @ BP [ HAWLEY . CONDENSED CHEM' D ICTNRY 9TH ED 119771 SOL IN ALL PROF`ORTIONS IN WATER & ALCOHOL, SOL IN ETHER ?y, BENZENE CWEAST., HDBK CHEM & PHYS 60TH ED 11979] INDEX OF REFRACTION: 1.4324 @ 2.0DEG C/D; SADTLER REFERENCE NUMBER: 267 (IR„ PRISM); 92 (IR, GRATING); 401(NMR',, VARIAN) [WEAST., HDBK CHEM & PHYS 60TH ED 19791 40i.1 DYNES/CM @ 25 DEG C[HAWLEY. CONDENSED CHEM' DICTNRY 9TH ED 19771 0.07 MM HG AT 20 DEG C[HAWLEY. CONDENSED CHEM' DICTNRY 9TH1 ED 1977] 0.581 POISE @ 20 DEG C [HAWLEY. CONDENSED CHEM D I CTNRY 9TH' ED 19771 SLIGHTLY ACRID TASTE; DENSITY 1'.0u!6 G 20 DE& C/4 DEG Cq FREEZES @! -59 DEG C; BP 1G8.2 DEG, C @ 7601MM. HG /DL-FORM/ [MERCK INDEX 9TH ED 19-76] OPTICAL ROTATION: -15.0 DEG' @ 20 DEG C/D; BOILING POINT 187-189 DES C @ 760 MM HG /L--FORM/ [MEFtCk=: INDEX 9TH1 ED 1976] MISCIBLE WITH WATER, ACETONE, CHLOROFORM;I SOL IN ETHER; IMMISCIBLE WITH' FIXED OILS /DL-FOrM/ CM'EnC{-=:: INDEX 9TH ED 1976] SPECIFIC HEAT: 0.590 CF,''Li:'i5 @ 20 DEC, C; HYGfiOSCOF'IC [HAWLEY. CONDENSED CHEM DICTNRY 9TH ED 1977] LOW /FIRE P-IAZA;!D/ WHEN EXPOSED TO HEAT OR FLAME; CAN REACT WITH OXIDIZING MATERIALS. [ SAX ., DANGER f='ROPS INDUS P'9A'TER 5TH ED 19791 '210 DEG F OC [HAWLEY., CONDENSED CHEM D I CT!?IRY 9TH ED 1.9771 700 DEG F[SAX.DANGEF< PROPS: IihiDUS MATER 5TH ED11979] /USE/' ALCOHOL FOAM. [SAX . DANGER PROPS INI)US MATER 5TH ED 19797 UPPER 12. 65., LOWER -2. `s%. MODERATE /EXPLOSIION! It(AZARD/ Wf-1Efi1 E{PCIS':=D TO FLAME. CSAk. DANGER PF.r1PSI I NDI IS MATER 5TH ED 1979 ] 874911216
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Hi1:}?MtEl`1'T METHODS Ai iD SHIPPING COhJ'TATh1F FiS.' [a!_A S{~ L~OTTLES:' ,D(iU1~S,l REGULATIONS TANE::: CARS•q TANE:; TFUCI«:;. [HAWLEY. CONDENSED ' CHEM D'DCTNRY 9TH ED 19773 STA.OI 1_TT`t'fSHELF LIFE CAN REACT WITH OXIDIZING MATERIALS [SAX'„ DANrECi F' oP i I'N[?;JS MATER 5TH ED 1979'] 'STAD I L I TY.' SHELF L I FE, STABLE UNDER ORLt I NAr:`r' COIUD'I T I ONS,, TENDS TO OXIDIZE AT HIGH TEMP CMEFtCk:: INDEX 9TH ED' 1976]1 IS SAID TO EsE' SIMILAR TO'i THAT OF TCin:Ii HAZARD iATIIN~~' 1., TOXICITY GLYCERINE & IS THEREFORE F'F`AC?'ICALLY' NONTOXIC. NO':UNTOWAF;D FEACTI'ONS DESCF;I&ED' IN MAN'.... 1= FRACTICALL`F NONTOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) IS ABOVE 15 G/KG'; FOR 70 F;G F'ErSON' (150 LB') ,, MORE THAN I OT (2.21 LB');., [GOSSELIN. CTCP 4TH' ED 1976] PQ I SON INr F'OTEN'~T I A'L PROPYLENE GLYC'7L... P9RESENTS ESSENT I ALLY NO Tt7XICITY' HAZARD. [ENCI"C OCCUF'A'T' HEALTH & SAFETY 197'1] ANT I DOTE AND EMERGENCY TREAT PT,, NOT THE F'O'I SC1N' I S MOST SUCCESSFUL. TREATMENT GENEF'AL kULE... /NON-TOXIC INGESTION/ C F",'UMACk:;. F O I S I NDEX 1'.975-F'FnESENT 7 HUMAN TOXICITY EXCERPTS PROPYLENE rIiYCCL IYIAY' CA'WSE HEMOGLOBINUF;'IC NEPHROSIS. CTHIENES. CLINTOk 5TH EID1972] HUMAN TOX ICITY EXCERPTS HUMAN.., HAVE BEEN EXPOSED TO SATURATED AND SUF'EFtSATURA T Ei7 riTMO`iP{-•IERES FOR ' F'F{OLONGED' F'EF; I Ofi9S. .. WI'.ThIOUT ADVERSE EFFECTS. ... EYE 3CF]NTACT. ..H'A'SNOT Q:AUSED A'NYEYE IF'F:ITATION... NOR WOULD SUCH BE EXPECTED. CF`ATT1^. INDUS HYG & IOX 'ND ED VOL2 196:3] HUMAN TOXICITY EXC; RF'TS ALTHOUGH NONINJURIOUS, A DROP APPLIED TO HII_MAN EYE CAUSES IMMEDIATE STINGING, SLEF'HAF:OSFASM &LAC :IM'ATI'ONi. . . DlSCOMFOF;'T LASTS FOR SEVEF;AL SEC UNTIL TEARS i' WASH.,..,AWAY. THIS I S FOLLO(tlED BY MILD ;I T'F;ANSIENT CONJUNCTIl;',AL HYF'EF;EMIA, BUT' NO. F;ESID>+~AL D'ISi~t~'ct•PFOF ;T•PFOF;T OR INJURY. [Gf'.ANT. TOX ;. OF THE EYE, 1`-r'7=F ] ~j HUMAN T O?;,IC'ITY EXCEI-:F"TS' O(•~i?LLY ADMIN F'F:CIF'YLEI'!E GLYCOL (,1-1. S1 G/}'1G)l i HAS REDUCED INTRAOCULAR i-i'fiESSUfiE... BY ~, RA I S I.Jr C SMOT IC PRESSURE OF TiLOOD.,..,I N II I-•IUMAN'... [G=:ANT. TOX OF THE EYE 19741] HUMAN TOXICITY EXCERPTS FROM FtESULTL, OF, ,, S&~.- HUMAN SUBJECTS WITH t,?AF<' I OU'_ DEF!r-1ATOL_OG I CAL L:ACF>-;GF;OUNDS, I T APPEARS ,, THAT I i'O;=YLENL. G LYCOL MAY CAUSE F'RI MAr:`r' SF;' T PN I RRI TAT I R''i~l! I h.~i SOME F'EOF'LE „ b hOr.Aj'LY DUE T0 DEHYIDRATION',, BUT MATERIAL D?.JES N1=T~ ryF'PEAn TO PE SENSITIZER. CPATT'r'. I'NDUS ITYllG ?>. i fD;, 22ND ED VOL22 19631 HUM~`yN TOXICITY EXCEFcF'T',4°-, ...!'IT/ AF'FF`EAf:S T& F-i0,'JE .-_`-`-EDATIVE-TYPE OF FwF FECT '<, Iti Gi_YCOCCtdI:I:C'... Cf-'A'TTY'. INDUS ITYr' & TOX 2ND ED 'JCL 87491217
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HUINAN 1"f ~-iI.=li`r' ~;:i._LF''T¢`, UNDIL FFF:Ot'YLE!!E GLYCOL TESTED ON SKIN OF MAN PRODUCED NO II[:9=i I TAT I OItil UNDER' OPEN CONDITI'ONS. CO'CCLUSIVE CONDITIONS F'RODUCF_D', SEVERE RESPONSE W I T}] ERYTHEMA, EDEMA & VE SICLES. REPEATED EX1='OSUF'E TO1 10 & '0"/.' FOR .^•_' Wh:: SUG .['.,ESTED REACT IONS DUE TO SWEAT RETF_NT I ON & WEAk:: F`R I MARY I RF I TAT IfIN. [MOTOYOSH'.I K ET AL; J SCCJ 13: 29-39 (11979)] h!Ohdi-+IUt1.°,hd TOX I C I TY W'I TH' LETHAL DOSAGE M I'CE D'I ED W I TH' DYSF`NEA. EXCERPTS AND CRAMFS. ... LOSS' OF EQUILIBRIUM, DEFRESSION, ANALGESIA, FINALLY DEATH AFTER PROLONGED MOR'IBUND' STATE., [BROWNING. TOX & METAB INDU'S SOLU 1965] NON-HUMAN TOXICITY' ...IiVINJECTION OF 1-1CfML IN RA'TSF'ROV0F,ED'EXCERPTS A TRANSITORY FALL IN BLOOD F`RESSURE'... 0. 215-c7.,^o ML/f'::G' WE'RE' FOLLOWED H;Y TRANSITORY D'IURESIS. [BROWNING. TOX & METAB INDUS SOLV 19657 NON-HUI"PAN TOXICITY ACUTE: SLIGHT DEGENERATIVE CHANGES INI EXCERPTS KI DNEYS' OF DOGS R'ECE I V I N&LARGE' I V' AND DIVIDED GASTRIC DOSES... [EsRDWN!ING. TOX & MIETAB!INDUS SOLV11~'r65] N(?N-HIJMAN TO7(IiCI'TY' WHEN' TESTED' BY APPLICATION TO RABBIT EYES EXCERPTS IT. .. CAUSED N&MOFE THAN TRANSIENT SLIGHT C?7NJUhICT I VAL HYPEREM I A. TESTS~ ON R'AE+BI T EYES FROM WHICHICORNEAL. EF`ITHELIUI'1. . . REMOVED. . . /SHOWED/' NO INJURY FROM I RR I GATT ON WI TI-I 50% ' SOLN' I N WATEF( FOR 5 MIN, BUT MO'DERATE REACTION TO...UNDI'LUTED PROPYLENE GLYCOL FOR' 5 MIN., [GRANT. TOX OF i" H E EYE 19741 NON-HUMAN TOXICITY INJECTION INTO 'JORTEX!VEIN OF ANIMAL EYES EXCERPTS (li_r.; 5 ML T'N 10 SEC )' ... CAUSED SF`ORAD I CALLY SLIGHT' SEROUS DETACHMENT OF RETINA '< SEF'AFAT I ON OF NONP I'GMENTED,FROM F' I GMENTED'. EPITHELIUM OF CLLIARY' BODY, BUT NO, DEGENERATION OF'RETINA & NO CYSTOID CHANGES IN! f'A{-,S PLANA OF' CILIARY BODY. [GRANT. TOX OF THE EYE 19747 NON-HUMAN TOXICITY ORALLY ADh1IIN FROi'YLENE GLYCOL ( 1-1 .5 EXCERPTS G/k::G)...REDUCED INTRAOCULAR FRESSURE IN RABBITS BY RAISING OSMOTIC PRESSURE OF L'LOOD... [GRANT. TOX OF THE' EYE 1'974] NON-HUMAN TOXICITY °.i.3 L OF PROPYLENE GLY(.OL_ GIVEN TO A HORSE EXCERPTS IN MIISTAV:E FOR MINERAL CiIL, CAUSED DEPRESSION & ATF3XIA,, WITH RECOVERY IN .' DAYS. 7.5 L WAS I~_ETFiIAL... /L+JHEN/ FED TOi DOGS AT RATE OF '2 G/t;.:(:/DAY FOR 2 YR, HAD NO ILL EFFECTS. [ CLr' Afi:H::E .VET TOX 19753 87491218'
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NslN-FIU?°IAN' TOXIC;IT.';` ... STL!~yIES D"aa'a(=1N`3TFRATLfJ : THAT RAT CAN EXCERPTS TOLERATE 101,. .,. IN Drilh:lL': `T_NG WATER WIT}10UT PHYSIOLOGIC I'MF'A IF2MENT. ... t'IONI-t::EYS & RATS /EXf'~1F;ED% TO ATMIrSF`HEF:ES SATURATED WITH WFRO,+'YLENE: GLYCOL VAF'OFi.. . /EXI'-'ERIENCE.D/ NO ADVERSE EFFECTS... AFTER PERIODS OF 12-18 M'0,.. C CASAE'",ETT. TOX I'COLOGY 1'975] NON-HUMAN TOX I'CIT ;`. ... R'I-"iTS /FED/ 2.45 & 41.,9%. . . IN DIIET.. . AVG' LXCERF`TS DAILY INTAKES OF' 0.9 TO' 1.77 ML/KG OVER 24 MO'.../SHOWED'/ NO S I GN''I FI CANT EFFECT ON GROWTH RATE. MICROSCOPIC EXAM OF TISSUE R'EVEA'LED VERY SLIGHT LIVER DAMAGE',, BUT NO' RENAL PATHOLOGY. .../'%O:/ IN DIET/ NO'T' WELL TOLERATED BY YOUNG: FtATS yy F'RODUC'I NG FEMALES..,UNABLE TO.../WEAN.YOUN'G/. [PATTY. INDUS, HYG & TOX 2ND' ED VOL2 19631 NON-HUMAN TO'XICITY TOF°ICALLY, IT APPEARS TO. BE, WELL TOLERATED EXCEF;F'TS IN HIGH CONCN ONI SKIN, EYE °< MUCOUS MEMBRANES OF MANY ANIMALS, ALTHOUGH IT PRODUCES FflF:T OF F'AI N OR ST ING SENSAT I ONS NOTED WITH'' ITS MIXTURES ON IM OR WOUND THERAF`Y. F`AFENTEF4ALLY' HIGHI DOSE&Pf,OD'UCE ~' TF;AN(:!UIiLIZING' OR DEF'(=;ESSANT ACTIONI. ... IV' USE FOR' SHEE'F'. .. F'F:ODUCES HEMOGLOE{INUF:IA. CFiOS SOFF'. HDBK VET DFtUGS~ 1974] il NON-HUMAN TOXICITY ORAL ADMIN' OF F'FtOF`YLENE GLYCOL TO RATS ('i' ML ~ EXCEFtPTS~ OF 90%/100 G E;'ODY' WT/7 DAYS) DID NOT AFFECT HEPATIC MICROSOMAL CYTOCROME P450 CONTENT'„ BUT STIMULATED ANILINE HYDROXYLASE & SL I GHTLY I NCF; CYTOCHROME B5 CONTENT °< Eif,OMOSULFOPHTHALEINI-BINDIiNG CAPACITY OF il CYTOSOL Z "-"FtACT'ION. CA1"fAl`1OTO T„ ADACHI Y4 GASTROENTEROL J:F'I't1•3-1: 359 ( 1i178)]' NON-HUMAN TOXICITY F'F;OF'YLENE GLYCOL (90%~) PRODUCED CONDUCTIVE EXCERPTS MIDDLE EAR F'f`OL-;LE.MS IN GU!INEAiF"IGS BUT THERE WAS NO LOSS OF HAIR CELLS ABOVE THAT FOUND I N NOF:MAL UNTREATED AN I MA'LS. C VEF.'NON J ET AL,j ARCH OTOLAE;YN'GOL 1!04: 726 (11978)11 NON-HUMAN TOXICITY IP ADMIN OF 0.1 ML PF;nF.YLENE GLYCOL TO MICE EXCERPTS CAUSED' CHROMOSOMAL ABEFtF'ATI:ON&IN SF`ERMATOCYTES. CFiAZV'I F ET AL; AF:OGYA (MANIPAL, I'hr11IFl) 5: 60-; 111979)] NON-HUMAN" TOXICITY IN CALVE.S iV INJECTIO;V' 01.= An, S=.REI+.N OF EXCERPTS OXYTETFtAC',`CLII°dE--hiCL IN PT?OPYL.ENE GLYCOL ~< PROPYLENE GLYCOL ALONE PRODUCED TRANSIENT (1 4 MI N) F'E!:R'.I ODS OF CAF'D I;OVASCULAR'. I)E=F'hESSION ~~~;Hrr'iF;ACTERI'ZED BY CARDIAC ASYSTOLE, SYSTEMIC HYF'OTENSION & DECF: F'ULI`10NF;f:'.Y & RENAL ARTE:IAL B:LOOD' FLO1+7. CGROS 7 DFC E'T AL;', AM' J VET FiFES 40: 7cB= ( 197 r ) a' 8'749I1219
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i•!0iV'r--~'rtL'.lNAtd 1 0X ICITY _ X C ER' F' T:= {-;UMANI TOX IC'I TY VALUES ;JON-HU1nAN ' TOXICITY VALUES NON-HUMAN TO'XICITY'VALUES NON HUMAN TOXIICITY'VALUES NON-HUMAN TOn'CITY VALUES NOP.I-HI.aMAN TO'X I C'I TY VALUES NON-HUMAN'TO'XICITY VALUES' NON°-HUMAN'TOX'ICITY VALUES :+41ON-HUMAN TOX'ICITY VALUES' NON-HUMAN TOXICITY VALUES' NON-HUMAN TOXICITY' uALUE& NON HUMAN TOXI'CITY'VALUES NON-HUMAN TOXICITY VALUES NO'N;-i HUMA'NI TOXICITYVA'LUES NON-HUMAhI TO X I C IITY VALUES EC'OTOXIC'ITY VALUES' ABSORF'T I!Oha ,, D I~=TR I BUT I'.ON' AND EXC RETION' ABSORPTIONI, DISI RI~a uTION AND EXC'n:ET I GN IYIETiaDOL I._'.~,M'/M'ETADOL TTES UNDILUTED PROPYLENE GLYCDL TESTED ON SKINS OF' RABBI''T.Gi'J I NEA 1=` I'C °'•. MINATURE SW'I hIE' PRODUCED N0 I i i'R I TAT I ON RESPONSE ON NORMAL SKINS USING, OCCLUSIVE a< OPEN TECHN'IG?UES~. [ MOTOYrJSH'.I f;'.; ET AL y J SCCJ' 13: 29-T9' (1979)11 IRRITANT DOSE HUMAIV' DERMAL 104 MGi=' DAYS INTERMITTENT; TOXIC EFFECT: MODERATE SKIN IRRITATIC]N; TDLO CHILD ORAL 91 MG/KG/56 WK;. TOXIC EFFECT: CNS EFFECTS. GNIOSH. REG TOX EFFECT CHEM, SUB ' 19'787 LD5U RATS OCnAL 21 G/F~::G [NIIOSH. REG TOX EFFECT CHEM' SUfi 19777 LD50 RATS INTRAPERITONEAL 13 G/f".G [ NII OSH'. REG TOX EFFECT CHEM SUR1977 ] LD50 RATS SUE{CUTANEOUS 28 G/k'G [NIOSH'. REG TOX EFFECT CHEM SUB 1977] LD50RATS INTRAMUSCULAR t01G/}.G [NIOSH. REG TOX'EFFECT CHEM SUB 1977:) LD50lMIICE SUDCUTANEOUS 18500MG/'t;G [ N I OSH. REG TOX' EFFECT CHEM SUB 19773 LD5ii MICE' ORAL 24, G'/K:G [NIOSH. REG TOX EFFECT CHEM SUB 1'977] LD50 M I CE I NTRAF'EF:I TONEAL 1'' 14c7<j MG/ k::G CNIOSH. REG TOX EFFECT' CHEMISUB 1977] LD50 MICE INTF'AVENOU&Qow MG/KG [N'IOSH. REG TOX EFFECT CHEMI SUFt' 1977]' LDLO RAb'D ITS I NTF:A'VENOUS 4200 MG /F='::G [NIOSH'. REG TOX EFFECT CHEM'SUD~1977] LDLO RABBITS INTRAMUSCULAR 6300 MG/KG, [NIO aH. REG TOX EFFECT CHEM SUB 19773 LD5c~:? DOGS ORAL 22 G1k`:G [NIOSH. RE&TOX EFFECT CHEM SUB 19777 LDv0 GUINEA PIGS O1-:iiL 19' G/t':G [NIOSH. F.EG TOX EFFECT' CHEM SUB 1977] IRRITANT DOSE RA'BDITS OCULAR 104 MG ENIOSH. REG TOX EFFECT CHEM SUB 1978'7' LDLO CHICKENS INTRAVENOUS 27' G/'F:::G [N',IOSH!. REG TOX EFFECT CHEM SUB 197831 AQUATIC TOXICITY: TLM: OVER 1t?0o PPM/96 HR [NIOSH'. REG TOX EFFECT CHEM SUB ?.977] FROMI 11/4 TO 1/2 OF ORAL DOSE SIVEhdI TO RATS, DOGS OR HL IMAN. .. F:F'FEAi;S' UNCHANGED IN URINE I+dITHIIh! 24 L-il~i. [PATTY. INDUS HYG 4~i TOX 2.ND ED'. VfrL2: 19C-,3-]' THE [eL`a`COLS ARE WELL AF=s?(Dr-iF;`D BY DIGESTIVE TRACT AS WELL A: FROM =:C & IM INJECTIONS. ,'GLYC:DLS.' C l-HIENrS. r_'LIN TOX CTH rD~ 1197-] INJECTED ItiaTO: ANIMALS, PART IS EXCRETED UNCHANGED,, i=AF:T IS OXID1ZED TO LACTIC ACID,& REMAlNDER IS CONJUGATED WITH GLYCU'ROlVIIC' ACI'D... [LEFAi.lX. FRAC TOX OF F`LASTICS' l968] 8749122Q
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THEF:AF'EUTI1~ USES EXPTAL i!'IE: AL4•`•:YLDIOLS WERE COMF'ARED TO ETHANOL OR F'YRAZOLE AS A1'-JTIDOTES IN' ETHYLENE GL YCOL TOX I C:I TY. PROPYLENE GLYCOL PROTECTED MICE. ALF-:~(L?'IOL AI`•aTIIDOTES ARE EFFECTIVE & MAY BE SAFER THAN E THANOL OR PYRAZOLES. CHOLMAN NW ET AL„ ALE=:YLUIOL ANTIDOTES TO'. ETHYLENE GLYCOL TOXICITY'I!N MICE; T'OXICOL AF'F'L PHARMACOL 49:. 385 (1979)1 THERAF'EUTIC: USES HYDROSCOPIC 'r'iG:EtdTS~(EG, F`F:OF'YLENE GLYCOL.. .) ARE ADDED /TO RESF` INHALANTS/ TO'REDUCE VISCOSITY OF BRONCHIAL SECRETIONS. [AMA DRUG EVAL 3RD ED 1977] THERAF'EUTIC USES OIhI!TMENT' CONTAINING APPROX 70% ' PROPYLENE GLYCOL HAS BEEN USED AS OSMOTIC AGENT WITH GOOD FIESULTS. I'N TREATMENT OF EDEMA OF CORNEA. CGRANT.TOX OF THE EYE 1974] T HERAF`EUT I C USES TOF' I CAL AFF'L I'CAT I ON OF 4(:)-6()% A0 SOLN OF PROPYLENE GLYCOL W I TH OCCLUS I ON HAS BEEN' REF'IIRTED TO CLE'AR SKIN IN X-LINKED ICHTHYOSIS i ICHTHYOSIS VU'LGARIS., EGOODM'AN'. PHARM BAS IS THERAf" 5TH ED 19753 THERAr'EUTIC USES VET:~ ORALLY, TO ELEVATE BLOOD1GLUCOSE LEVELS I N F'ROF'HYLAX I S & TREATMENT OF ACETONEM I A I N' CATTLE. F'AL ATABILIT'Y IS OFTENI POOR, BUT IT IS~ INEXF'ENSIVE. GROSSOFF. HDEik,: VET DRUGS 19741' DRUG WARNINGS TOPICAL EAR DROPS CONTAINING HIGH CONCN OF PROF'YLENE GLYCOL ARE CONTRAINDICATED IN, CASES' W IlTH F'ERF'ORIAT I'ON OF TYMF'A'N I C MEMBRANE. C VEF:NOt•t J, I=RUM'METT R, WALSH T; ARCH OTOLARYNGOL 1 04'.: 726(' 1978)' 1 PROBABLE EXPOSURES INDUSTRIAL EXPOSURES ARE FROM DIRECT CONTACT„ OR FROM' INHALAT'ION OF VAPORS & OF MISTS WHERE MATERIAL IS HEATED~ OR VIOLENTLY' AGITATED. OTHER EXPOSURE IS BY INGESTION RESULTING' FROM' ITS~ USE IN FOODS & DRUGS. LF'ATTY. INDUS ITYG N: TOX :ND ED VOL2. 19631 F'ROBAr<'LE EXPOSURES S.INCL'-" ETHYLENE GLYCOL...I=•RESENT NO SIGNIFICANT HAZAFiDS, U114DER Nt1RMAL, INDUST rONDITIONc~, NO~NEED EXISTS FOR SF'ECI'AL INDUST !-IYGIENE MEASURES....HOWEV'ER'.... IT IS ADV I SABLE TC7i F'R'OTECT PERSONNEL BY ENCLOS I NG F'ROCES S ' OR PROV I D I N[3 LOC AL E XHAUST VENTIL_ATION'. S}'~':Ilq & EYE F'r'OTECTION' SHOULD ALSO BE WORN... /GLYCOLS & DERI4'ATIVES/ f_ENCYC. Ot:'r'L11:"'AT 'HEA11_TH & SAFETY 19711 PROBABLE E XF'OS UIi:ES APPARENTLY THERE ARE NO REPORTED I'NDUSTR IAL HAZAIi'PS FROO fi'11 THIS: MATERIAL. CCASARETT. TOXICOLOGY 19751 ANALYT I C LABORATORY ALL G:OSM'I?"T I CS': GAS CI',{RGMA'TOGF;AF'HY & GLC METFIODSy' COLUMN; 1'^2. TOBACCO:. GAS' & COLUMN CHROMATOGRAF'HY; T6. 01'6 & 1'?.Y ()t:y6. DRUGS VAN'ILL.A EXTF;Af'TS:. TI,TIR'r`aTION. EADAC. 1iiTH' ED 11965 AND I=OLLLIWIiki!:1 EDS] 87491221
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The BRS AidPage 9,~for ~ iAZARDLINE' BIt,S ~ LabeE HZDB Scope: The HAZARDLIN'E' database. provides regulatory, handling, identiiff<cation, an& emergency care infbrmation for over 3,000 hazardous substances. The'n information in HZDB is gatheredd from i regulations issued by state and U.S. gp'vern'ment agencies, court decisions, books and' jpurnal articles, iniorder to assemble a comprehensiwe' record for each, substance:. Producer Occupational Health. Services, Inc. PIO. Box 1505 400 Plaza Dhive' Secaucus. N)j 07094 Contact: Almcal Marochini 201-865-7500 ext 554 800-223-8978 (outside New Jersey) Years of Coverage: Current in6ormatlion ToUal Size: Records fbr ouer 31000 chemicall substances (September 1984) Updates: Mont hlly: BIBL Paragraphs: AN. CN, SY, RN. PD! RECORD STR~ ~LJCTLIRE KEY Label Paragraph Function Example AN Accession Number ..s 8C)9.an. 8408.an. Update Code " ..s 8408.up. I _1/1 up > 6405 CNi Chemical Name ..s ethanollcn. SY Synonyiiis' ..s grain adj' alc(jhulJsy. RN Registry Number ..s 64-17-5,rn. c2h6o.rn. PD Physical Description ..s txdorless, with i liyuidlpd: CI Chemical Information s grain adjialcuhu6.ci. I(SuperLu6el for 64-17-5:ci. CN. SY; RN and PD) a2h63r.ci. aolorless with: liyuid.ci. EL Permissihle Exposure display El. 1()00 PPMI OSHA TWA IC In(:nmpa(]hlhtn.`S ..4 4trnnF; iHll',,acids.7(:.. CL CFdhing displSrv CL,WEAR'IMPER-- VI(7t lS' CI.f)Tl i'I N( : RP' Rhspirau>r~ Seka:tiurr displav, RP' NONE; Sf'FiC- . AI'.IVItiE - tit'JPPLI'EID- r\IR RG31?IRdYT(lR'. M'S ~ht'rJii.d tiurvaillani:e ..s I hlih,d itdj r.nunt.ms. Label Paragraph~ Funcliom Exampk: RE Route of Entry' ..s skin~witih camtac(.re. TO Tarket, Oigtns ..s respiratory adj system.ln: SP Symptoms ..s dizziness with unsteady.sp: s~797sfr: FA First Aidl ..s wash with, siwp:fH: DT Diay;nostic Tlwls ..s liver adj,prnfilr.dl. RS'. 'RlxulatoryStatus ..s ':.xk:fr191[1.941:rs. I clean adj air act.rs. CT Civlificauons display CT DOCUIMrNTS'. SAVED FOR EMPI:OYE:F. R[Y:ORDSi HEAL'1'1-i S'rAil'IitS CLASSIFICATION 1S' l:raks„Spills, Fire. ..s dry adi chemical uilj' Evacuatian i exilinµuishnrs.ls. I WD Waste Disiwis:d ..s Irnnspcnl5' with was,h.wd. i f9'r llullrlin s brain adi d:unaytie.Ut. i N'1" Nliths ..y unlxirn :wljI children.nt. i Ox:' Oi:¢un Pncc 'I':drle di+plin' . 48 1, I )n,84,
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( ~KS? W Z i AN ACCESSION NUI'1'EERn ?192., 8508. CN CHEMICAL NAME: PROPYLENE GLYCOL. SY SYNONYMS: 1i, '2-PROPANED'IiOL. METHYL GLYCOL. 1, 2-F'ROF'YLENE GLYCOL. MONOP'ROFYLENE' GLYCOL. 11,~2-DIHYDROX:YF'ROF`ANE.. PG 12'., METHYLETHYLENE GLYCOL. FROPANE-1I,2-DIO'L. ALF'HAr-F'ROF'YLEIVEGLYCOL. TfiIMETHYL GLYCOL.. SIRLElVE. METHYL ETH1`LENE' GLYCOL. RN CAS NUMBER: J7-JJ-6., REG. TOX I'C' NUMBER: TY200000c_>., PD: CHEMICAL FORMULA: C•.~H802. PHYSIlCAL DESCRIlPTION: COLOR'LESS, ALMOST ODOF.LESS , SL I GHTLY V'I SCOUS L I G?U I D' SLIGHTLY ACRID TASTE. MOL WT: BOILING F'T:. SOLUB'ILITY: FLASH PT: VAPOF:'. F'RES: MELT P~T: UEL I N ' A,I R,: 76.11 372' F SOLUBLE 215-22S F (OC) 0.1:,:: MM. -24 F 1'i. Sy LEL IN AIR: 2.,6% MEC IN AIR: 700 F SPEC GRAVITY: 1., 036 1 VAPOR' DENSITY:, . 2.52 ODOR'. THRESHOLD: OCTANOL/WATER' C O-EFF I C'I ENT : -1.41/'-0.30. (CALC. ) ..
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E C- PERMISSADLE EX'POSURE: NONE ESTAFiLISHED TERATOGENIC DATA (RTEC) MUTAGENIC DATA (f~;TEC) II.'ERCLA HAZARD RA'TINrS - TOXICITY ~a - IGNITAL:ILITY 1-- REACTIVITY C! •- PERS I STENCE 0 TOXI'COLOGY: INDUSTRIAL EXPOSURE TO F'ROF'YLENE GLYCOL IS MAINLY FROM. S f•'•. I N CONTACT OR' I NHALAT I ON OF' VAPORS OF; M'I STS' FROM' HEATED L I GIU I'D'. THE HEALTH HAZARD IS NEGLIGIBLE F'OR' NORMAL HANDLING. THE FDA ALLOWS THE USE OF PROPYLENE GLYCOL IN FOOD AND COSMETI'CS. INGESTION OF MASSIVE DOSE& WILL CAUSE GASTRO'I NTEST I NAL UPSET AND UN!COfilSC I OUSNESS. ALCOHOL I'C INTAKE ENHANCES THE TOXIC EFFECT. EYE CONTACT IS NOT INJURIOUS, BUT MAY CAUSE LACR IMAT I ON', ST I NG I N!G', OF' BLEF'HAROSF'ASM. SK'I N. CONTACT CAN'. F'RODUCE PRIMARY IR'RITATION!, BUT' NOT' SENSITIZAT'ION'. ORL-CHD TDLO: 7'9' GM'/I!G15b WK-INTERMITTENT ORL-RAT LD501: 20 GM/KG ORL-MUS LD5G: 24 GM'/k'G ORL-DOG LD50: 22 GM/KG ORL-RBT LDLO: 20:GM/KG ORL-GPG LD50: 19 GM/KG' SKN-R'BT LDO0:208c:>01MG/KG OSH'A:STANDARD~ 29CFR19'10'.120t:)~HAZARD COMMUNICATION REQUIRES CHEMICAL MANUFACTURERS AND IMPORTERS TO ASSESS THE HAZARDS OF CHEMICALS WHICH. THEY' PRODUCE OR I MPORT, AND ALL EMPLOYERS N-IAV'I NG WORKPLACES I N'. THE MANUFACTURING D'IVISION,, STANDARD INDUSTRIAL CLASSIFICATION CODES 20 THROUGH 39, TO F`ROV I DE I NFORMAT I ON TO THE I R EMPLOYEES CONCERN I NG H'AZARDOUS CHEi"1ICALS BY MEANS' OF' HAZARD COMi`'IUNIICATION F'ROGRAM~ INCLUDING LABELS, MATERIAL SAFETY DATA SHEETS, TRAIN'IN!G, AND ACCESS' TO WRITTEN'RECORDS 48FR5.J28<-Y11/25/8? FOLLOWING OSHA STANDARDS APPLICABLE TO SUBSTANCES LISTED 29CFR1910, OTHERWISE ADVISE., DANGEROUS EXFOSURE': NONE SPECIFIED COLORLESS, ALMOST OD'ORLESS, SL. IC INCOMFATIB'ILITIES:. STRONG OXIDIZERS. METALS. MAY FORM EXPLOSIVE PEROXIDE(S). VAPOR-AIR MIIX.TURES ARE EXPLOSIVE ABOVE FLASH F'OINT'! .
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CLOTHING: Eh'IF`i_i1YERS SHALL F`TtOVIDE AND' ENr URE THAT EMFI~_OYEES USE AF'F'F{OF'Ft'IATE F'fiOTECT IVE CLOTH I'NG AND EC?U I F'I''IENT NECESSARY TO' PREVENT EEF'EATED' OR F`F'OLjCN6ED SF•::INI CONTACT WITH TH!IS SIII:S-IlANrE. FACE SHIELDS, SHALL COMPLY WITH 29C=R1'Sil~) 1~ '(F;? (_"') , (A) (4) , (.'A)'!.'5), ANI"J (A) (6). EMPLOYERS SHALL ENSUFtE THAT CLOTHIN&CONTAMINATED WITH THIS SUBSTANCE IS' F'LACED I1V CLOSED COCUTA I'NEFtS FOR STORAGE UNT I L I T CAN' BE' D I SCAFDED OR UNT I L THE EMPLOYER F'F:OV I DES FOR THE REMOVAL OF THE CONTAMINANT FROM THE CIiOTHIhlG., IF THE' CLOTHING~ IS TO' EiE LAUNDERED OFt. OTHERWISE CLEANED TO REMOVE THE' CONTAM'I'NANT, THE EMF'LOYEF; SHALL I NFORM THE PERSON F'ERFOF.M I Nr THE CLEAN I haG OF THE HAZAFDOUS PROPERTIES OF THE SUBSTANCE. _ ACGIH "GU'.IDELINES,FOf~ SELECTION OFCHEM'I'CAL F`F(OTiE.CTIV EE.CTIVE CLOTHING" I'NDI'CATES THE' FOLLOWING MATEF;IALSAND F'Ftt'OTECTIVE FcATINGS~ EsY' I NDEF'ENDENT VENDOF:S' AGA I NST ALIF'HATIC' AN!D!ALICYCLIC HYDF:'OCAF:BONS:~ EXCELLENT/GOOD: NEOPRENE NITRILE RUBBER F`OLY'UF:'ETHANE POLYVINYL ALCOHOL VITON GOOD/FAIF',: CHLOF; I NATED POLYETHYLENE FA I F,/F'OOF:',: BUTYL RUBBER NATURAL RUBBER NEOFF,ENE/NATURAL RU'E+DERF'OLYVINYL CHLORIDE FAIFt/GOOD: NEOPRENE/STYRENE-BUTADIENE RUBBER NITRILE/POLYVINYL CHLORIDE F'OLYE'THYLENE STYFtENE-EsUTADIENE RUBBER. WEAR' EY'EFFi'OTECTIOt'UTO F'EEVENT:NONE REQUIRED. EMPLOYEE SHOULD WA'SH: EMF'LOYERS~SHALL ENSURE THAT EMPLOYEES WHOSE SKIN BECOMES CONTAMINATED WITH THIS SUBSTANCE PROMPTLY WASH OR SHOWEFi' TO F<EMOVE' ANY CONTAM I N'AhIT FF.OM THE SKI N. EMF•LOYERSSHALL ENSURE THAT EMF'tiOYEES WHO~F-IAdNDLE THIS SUBSTANCE WASHI THE I F{ HAIVDS THOROUGHLY BEFORE EAT'I'NG, SMOI:';I NG , Or. US IiNG TO I LEl" FACILITIESI. WORK CLOTHING SHOULD BE CHANVED' DAILY:. NOT F:EQUIFtED. REMOVE CLOTHIING': EMF'LOYEF S' SHALL ENSURE THAT NON- I MF'Ef;V I OU ; CLOTH I1VG WH I CH BECOMES CONTAMINATED WITH T}-III&SUDSTANCE' BE REM'OVED' PROMPTLY AND NOT REWORN UNT IL THE SUE{STANCE I S REMOVED FROM THE CLOTH I NG . THE FOLLOWI h1G EG!l:1 I F'MENT SHOULD BE AVA I LA'BL.E : NONE REQUIRED.
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RESFIRATOR'SELECTION (UPPER LIMIT DEVICES PERMITTED'.) : HI'GH LEi:%ELS - GAS I`9ASf;:: WITH AN ORGANIC VAPOR CANISTE F (CI-i I hl'-STYLE ORFRONiTOR BACK-MOUNTED C'ANI STEF' ) - SELF-CONTAINED BREATHING APPARATUS i F IF,'EF I GHT II':IG - SELF-CONTA I hIED BF,EA'TH ING' APPARATUS' WITH A FULL FACE-F' I ECE OPERATED IN F`FiESSURE.-DEMAND' OR F'OSI T I VE-F'Ft'ESSUFtE' M'OD'E. MS MED'IC'AL SURVEILLANCE: NO NIOSHVOSHA'DATA, ADVISE: EKG RECOMMENDED IF EMPLOYEE TO WEAR FULL-FACE RESPI RA'TOR ., GENERAL MED'I CAL H I STORY'. 40CFR717 FtECOI-iDS~ AND,REROf,'TS' OF ALLEGATIONS THAT CHEMICAL SUDSTANCES CAUSE SIGNIFICANT ADVERSE'FiEACTLONS TO HEALTH'.OR!THE' ENVIRONMENT TOXIC SUBSTANCES CONTROL ACT ('TSCA) ' SECTION 8(C) RULE REQUIRES' MANUFACTURERS AND'C~ER'TAIiNF'~ROCE~SSORS OF CHEMICAL SUBSTANCES AND MI XTURES TO KEEP F.'ECORDS OF S'I GN!I FI CANT' ADVERSE REACT I ONS TO EMPLOYEE HEALTH FOR 1'0 YEARS 48FFt'38187' 08/2z'/'8': 48FF:39225oBJ,'.U'/8:'•:, (EFFECTIVE DATE CORRECTION)., PHYSICIAN EXAMINATION INDUSTRIAL EXPOSURE HISTORY. PRE-PLACEMENT AND ANNUAL EXAMS. MEDICAL WARNING'FOR'REFUSAL OF MEDICAL EXAMINATION. RE ROUTE OF ENTRY:: I NHALAT I ON. INGESTION., Sk; I N OR EYE CONTACT. TO TARGET ORGANS: EYE'S'., SF::INI. CENTRAL NEFtVOUS SYSTEM. GASTROINTESTINAL. KIDNEYS.
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S F, SYMPTOMS: S}::IN, COVERING OF DOD'r' (SC('~174)~, IRRITATION, EXTREME REACTION TO A CONDITION (SL:isc=)9ii). EYE,, ORGAN OF SIGHT (SCt:1170); IRRITATION, EXTREME F;EACTION TO' A CONDITI'i'lN LACF;IMAT7:[)N, D I SCHARGE OF TEARS ( SCi fs i96 ). HYF'OGLYCEM I A, AEMNORf•iALLY LOW BLOOD SUGAF;' (SC{?321 )'. CENTFAL, NERVOU'S SYSTEM,, F'EFiTAINING TO NEURAL E'O'DY SYSTEM (SC00t8)1;. DEF'RESSION, DE'CREASE' INI ACTIVITY/FUNCTION (SC004') . MUCOUS MEMDRANE, MEMBRANE L I h1!I NG PAS SAGES /CAV I T I ES ( SCO1 o9 ); I F:F;'I TAT I ON, EXTREME REACTI ON TO A COND I T I ON' ( SC0090!) . NAFtC;OS I S', STUPOR OF" SLEEP DUE TO NAF:COT I C ( SCc11 13)! . HEADACHE, F`A IN I N HEAD OR CRAN'I UM AREA ( SCO075). NAUSEA,, S'I CKNESS AT THE STOMACH' ( SC« 1'11 5)' . VISUAL D!ISTUF:BANCE„ UPSET IN SIGHT (SCO1165)1. VOMITING, PERTAINING TO' NAUSEA,(!SCr1166). ABD'OM I NAL , RELAT I NG TO THE ABDOMEN ( SC0U01); SF'ASM,, CONVULSIVE'MUSCULARCONTR'ACTION (SC01W'). k::TDNEY DAMAGE, INJURY TO THE KIDNEY (SC0220) ; IN EXPERIMENTAL ANIMALS, (SC0212). REPRODUCTIVE EFFECTS, BI'F:TH DEFECTS (SCo2.81 )'; IN EXF'EF:I MENTAL AN'I MALS, ( SC021 2.). FA FIRST AID. (1 OF 4), I F TH'I S CHEM!I CAL GETS I NTO1THE' E4'ES, IMMEDIATELY WASHI THE EYES W I TH LARGE AMOUNTS OF WATER, OCCAS I ONALLY L I FT I NG THE LOWEF' ANDi UF'F'EFt LIDS. GET'MEDICAL ATTENTION'.IMMEIDIATELY. CONTACT LENSES SHOULD NOT BE WORN WHEN WORKING WITH THIS. CHEMICAL. (2 OF 4') I F TH'I S CHEM!I CAL GETS ON' THE Sf•: I N', I M'MED I ATELY WASH CONTAhi1I NATED St: I N W'I TH SOAP OR,M IILD DETEF:GEN Il & WA'TER:. I F TH I S CHEM I CAL SOAKS CLOTHING, IMMEDIATELY REMOVE CLOTHING & WASH SKIN WITH SOAP OR MILD DETERGENT & WATEFt. GET MEDICAL ATTENTION F9?cOMF'TLY'. (,-:' OF 4 ) I F A PERSON BREATHES I N LARGE AMOUNTS OF TH I'S CHEM ICAL, MOVE TH'E EXPOSED F'EFtSON', TO' FFiESH' AIF:, AT' ONCE., IF BE":EATHING' HAS' STOFF'ED' PERFORM AB:T I F I'C I AL F<ESF' I'FATI ON. KEEP THE AFFECTED PERSON WARM AND AT FcE ST. GET MEDICAL ATTENTION A&SOON AS POSSIBLE. DT (4: OF 4) WHEN THIS CHEMICAL HAS DEEN' SWALLOWED AND PERSONI IiS CONSCIO!!S, I MMED I ATELY G IVE PERSON LARGE r!UANT I T I ES OF WATEF:'. A'FT'E:R' WATER HAS BEEN SWALLOWED,, TRY TO GET THE PERSON TO VOMIT BY HAVING HIM TOUCHI THE' BACK OF H I S TH ROAT WI TH HI S F I NGER'. DO NOT MAKE AN UNCONSC I OUS PERSON VOh1I T. GET htED'I CAL ATTENT I'ON I MM'ED I ATELY . Gb' SPECIAL DIAGNOSTIC TESTS AND' INDEXES OF EkFYOSUFiE: ~ LIVEFi' PROFILE E;LOOD~ TE'STS'. rA ~ ~ IV d1~' ~'
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5S REGULATORY STATUS. (1 OF 1:_i OSHA STANDARD '29CFF;1910.12200 HAZAF,D COMMUNI'CAT'PON REQUIRES CHEMICAL MANUFAC TIiREF;S AND IMF`.rJF,:TERS TO A SSESS THE tdAZA'F'-DS OF CHEMICALS WHI'CH THEY FFtOD'UCE OF:' IMPORT, AND ALL EMF'LOYERS~ HAV'ING WOFiI-"!F'LACES~ IN THE MANUFACTURING D'IVISI'ONi, STANDARD INDUSTRIAL CLASSIFICATION CODES 20 THROUGH -''9', TO F'ROV I DE I NFOF;MAT LON TO THE I R EMF'LOYEES' CONCEF;N I NG HAZARDOUS CHEMICALS BY MEANSiOF HAZARD COMMUNICATION PROGRAM INCLUDING LABELS, MATERIAL SAFETY' DATA SHEETS, TRAINING, AND'ACCESS TO' WEI'TTENI RECORDS 48FF.S32801111/2S/83 FOLL.OW'IfVG OSHA' STANDARDS APPLICABLE TO SUBSTANCES LISTED 29CFR191!cD, OTHERWISE ADVISE. (2 OF 12) OSHA STANDARD 29CFR1910.94 VENTILATION OSHA STANDARD c9CFFt1910.1i4 RESF'IRATOF;Y PROTECTION. (Z-5 OF 112) OSHA' STANDAFtD 29CFF;1910. 20 ACCESS TO EMPLOYEE EXPOSURE ANID:MEDICAL BECOF:DS',. ( 4' OF' 112) OSHA STANDARD ^9CFR1910.132 PERSONAL PROTECTIVE EG?U'IF'MENT., (15 OF' 12), OSHA STANDARD 29CFF~1I91'0.141 SANITATION. (6 OF' 12) OSHA STANDARD 29CFR1191 0. 1 S'1 MED I CAL SEt;V TCES AND F I FST A ID. (7 OF 12) 'OSHA STANDARD 29CFF,191 s1., 1:`~ EYE AND FACE F'FOTECT I ONi. (t3 OF 12.) 40CFR717 RECORDS AND REPORTS OF ALLECAT I ONS THAT CHEM I CAL SUBSTANCES CAUSE S I GN'I F I CANT ADVERSE FtEACT I ONS TO HEALTH OR THE ENV IT'~ONM'ENT f'EC!UIEES MANUFACTURERS AND' CERTAIN F'F;t7CESSOF.S OF CHEMICAL SUBSTANCES AND M I XTURES TO F::EEP RECORDS OF S'I GN I F I CA1VT ADVERSE FiEACT I'ONS TO HEALTH OR THE ENVIRONMENT ALLEGED TO HAVE DEEN'CAUSED' BY A SUBSTANCE OR M'IXTIJF:E. EPA MAY INSPECT AND REQUIRE REPORTING OF SUCHI F,'ECOf,DS'.l 48FR3:!'81 7 8 019/222/8 _ . (9 OF' 12) SUBSTANCE LISTED TOXIC SUBSTANCES CONTFOL ACT INVENTOFa'-. (10 OF 12) TECHNICAL ASSISTANCE DATA COMF'LET'ED/F'UBLISHED CLEAN WATEF:' ACT SECTION :31'1. (Cl1A) ( 1 1 OF 12) FEGULATION' PROMULGATED RESOURCE CONSERVATION AND RECOVERY ACT (F;'CFiA)' 41()CFF.`'26(?1. 874g1228
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(12 OF 1^. EF'ISODE' htEF'OF:T Ii4DEVE_LOF'MENTiF'ROGFt,ESS CLEAN WATER ACT (C4+JA). CT DOCUMENTS' SAVED FOR EMPLOYEE RECORDS: NO FEDERAL AGENCY FiEG?UI'REMEI1T,, BUT DUE TO -HAZAf".DOU,.-~ NATI_IIFEE OF SUBSTANCE, ADV'ISE FOLLOWING: HEALTH STATUS CLASSIFT'CATION. OSMA RESF` I RATOF; CEF;T I F I CAT I'ON 29CFFi 19'1 c). 1=4 . DEPARTMENT OF TRANSPORTATION IF OF'ERATES~HEAVY EG?UI'PMENT. EMPLOYEE HAZAKD'OUSh1ATEkIALS EDUCATION RECEIPT. EMPLOYEE MEDICAL RECORDS RECEIPT TOX IC SUBSTANCES CONTROL ACT' (TSCA) SECTION B(C) RULE F'EG?UIRES MANUFACTURERS AND CEF.TAIN' F'F:OCESSORS OF CHEMI CA'L SUBSTANCES AND MII XTUfiES TO f~>:EEF" BECOF'DS OF S IGN I F I CANT ADVERSE REACTIONS TO EMPLOYEE HEALTH FOR 30 YEARS:. CONTACT: JACK F'. MCCARTHY, OFFICE OF TOXIC SUDSTANCES, EPA (80t7;)424-1404. 48FF;38178' 8/22/83. MEDICAL WARNING FiEL•7UIFED FOR MEDICAL EXAMI REFUSAL SIGNED BY EMPLOYEE. LS LEAlKS,, SFILL'LS~.,i FIRE ANDi EVAOUATIONPIROICEDURES. DEPARTMENT OF TFANSF'OF';TAT ION HAZAE,D CLASS 49CFFi172'.101 HAZ'AfiDOUSI MATERIALS TABLE. NOT LISTED. INTERGOVERNMENTAL MARITIME ORGANIZATION HAZARD CLASS' 49CFFt17:.102 OPTIONAL HAZARDOUS MATERIALS TABLE. NOT LISTED. L I ST'ED BY U. S. COAST GUARD UNDEF:' CAFGO COMF'AT I8I L I TY GF:OUF" ALCOHOLSGLYCOLS, INCOMPA'T'IEsLEWITH THEFOLLOWIN&MATEF;I'A'LSt SULFUFIC'ACID, NITRIC ACID, CAUSTICS, ALIPHATIC AMINES:,. ISOCYANATES. "
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WD WASTE DISPOSAL. ( 1 i:J F 1 ) THIS MATERIAL NOT L_ISTED AS HAZARDOUS SUBSTANCE,, AS DEFINED IPJI SECT 11. ta i, ( 14) OF' THE COMPREHENS I Vi:=, EflV"1: Ftr]1tilMENTAL RESF'ONSE, COMF'EPNSAT I ON,, AL I ABI L IiTY ACT ( CEF;CLA ) t7F' 1980, FPURSUANT TO ONE OR MORE OF THE FOLLOWING: * FEDERAL WATER POLLUTION CONTROL ACT (FWF'CFi) SE'CTION' 311 (B) (2) (A) * SOLID WASTE DISPOSAL ACT SECTION * ' CLEAN WATER ACT (CWA)' SECTIONI ?«7 (A) * CLE'AN AIR ACT (CAA)' SECTION'. 112* T'O )Q I C SUBSTANCES CONTROL ACT ( TSCA) SECT I ON 7 * COMPREHENSIVE ENVIF:ONMENTAL RESPONSE, COMPENSATION,, AND LIABILIT ACT (CEFtCLA) SECTION 102'. NT NOTES,: FiEACTS WITH LIGHT METALS, FOFiMING'. FLAM'MAEsLE' HYDROGEN GAS. ATTAC}k:S MANY' PLASTICS.. OC PARAGRAPH SENTENCE NS-WORD RN (1) 2 ^.
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i,ineering to the cs it dilficult for :eecied fur: plant he field. -uf;h nKricvlture, -ductx, nutrition, ; 5 subjects con, rrtinent, data. Volume 2 of the -u t hia encyckape- -ubjects covered. ; ience dii:cipliner. great - --rietv of ;woultt, 1It andl Source Boo of F'iavors HENRY H: HATH~ LWIAF., B. Plharm, M.F.G., F.P.S., F.I.F.S.T: i:5ultan Bush Boake Alllen, A Division of'Albriglnt & Witson, Ltd. ikectgoxxis, dairy Londbn, England -oducts fhom, the, ,Iume;n the fieldI THE AVI PI:JBLISH'ING, COMPANY, INC. e reference work, It is organized in Westport, Connecticut, U.S.A. .cript iuns of food. , ndhook of'. A to Z' ti[lg il tnrm, which gives 0
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ORGANIC CHEIIIICAIS USED IN FLAVORINGS AND FRAGRANCES The following data for organic chemicals is pre- sented in tabular alphabetical format to providee ready source of information which is of direct and immediate concern to the flavoriat engaged in com- pounding imitation flavorings. The list provides in- formation on: (a) The usually accepted chemical name or com- mon name if this is the more familiar usage. Ihl Principal synonym(s), where these are of val- ue in correctly identifying the chemical. Icl The FEMA and/or IOFI classification num- ber which also aids identification. The fol- lo:ving symbols are used in the tables: Art a artificial Art+ s artificial but included in the IOFI positive list' NI = naturevidentical NOTE: Flavoring substances appearing in the FEMA GRAS lists are sequentially numbered as follows: GRAS 3; 2001-3124; GRAS 4, 3125-3249; GRAS 5; 3250-3325, GRAS 6, 3326-3390; GRAS 7, 3391=3423; GRAS 8, 3424-344A; GRAS 9, 3445-3475; GRAS 10; 3476-3525; GRAS 11, 3628= 3596; GRAS 12, 3597=3650. 'IOFI Code of.Practice for the Flnvour industry,tkt.20, 1978 as amended May 1980. ZeztsW4s (dl Solubility data particularly in ethanol, water, propylene glycol and fixed oils. The com- pounding of flavorings involves the blending together-of ingredients of wide physical dis- parity; this being achieved by the use of per= mitted solvents of which those quoted are moat widely used. The following symbols are used in the tables: In - insoluble VSI - very slightly soluble SI ~ slightly soluble S=soluble VS - very soluble M = miscible lel Boiling point and flash point, which are of value in determining the relative stability and safety in handling of a flavoring, par- ticularly where the product is intended to be spray-dried. (f) Legal status in the United States, particular- ly whether the chemical is found in nature. Following the tabular data given below is a sup= plementary tabular listing of additional synonyms cross-referenced to the generally-accepted chemi- cal name in the main body of information. Sources: The following sources of information used in compiling the data given below are gratefully acknowledged: 332 ORGANIC CHEMICALS USED IN FLAt'ORItGS AND FRAGRANt-E,S :113 ARCTANDER, S. 1969. Perfume and Flavor Chemicals (Aroma chemicals), Vol I and II: Stcffert Arctander, lilontclnir, N:1. COUNCIL OF EUIt01'E. 1974: tiaaual Fla- vouring Substances, Thcir Sources and Added Ar- tiRcial- Flavouring Substances. (Maisonneuve S:A:;. Moulins•LecAtetz; France), Strasbourg, France. EOA: Updated to 1975.- Specifications and Stan- dards. Essential Oil Association of US.A., 60 Eaet 42nd St., New York. FOOD CHEMICALS CODEX, 2nd Edition. 1972. National Academy of Sciences, Washington. D.C. FORD, R.A. and CRAMER, Glt. 1977. Refer- ence list of flavoring substances in use in the l!nited States. Perfum. Flavorist 2; (1), 9-62. FURIA, T.E. and BELLANCA, N. (Editors) 1975.-Fenaroli'a Handbook of Flavor Ingredi- ents; 2nd Edition. C.R.C. Press. Cleveland. GRUNDSCHOBER, F: ct al. 1975. Survey of worldwide use levels of artificial flavouring sub= stances. Int. Flavours Food Additives B, 227- 21t1. HA1.1„ R.I:. lfifu; H,11:L, R L: nn+l t11'F.it. It.):. 1961. N1'J!ii; 1970; ~t)SER. H.L. and IIALI.: R.L. 1972. 1`I"1; OSER. R.L. and FURI). H.A. 197 5. 19T7. efti9. Ftecent iir+-gre- + in the tvn:itienr tiun of flnPorlnR ingredient, under the F.,,:d Additii'e+ Atnendntent: F+rid Te+hnid. 14. t IO), 4AH•, 1.i;112k 2r): 19.(21. Part 2. 151 24.t.,l, :3; 26,151;3i;2i,111,6i,2i.fll/;Sti;.R-191;:6;2A, (8), 70t .71; (1), 65; .72, (2), fir>t .7.7; (7), 65. 1\TF;RNATIONAL ORGAXI7.AT1O\ OF THE FLAVOR INDt'tiTRI'. 1978: Pii,itia•e li~t of anificial flavuifrinR subaancev. tInfr,rrn. circ.). MAFF. 1976. Ralyut on the Review of Flacour- ings in Fuad. Frrid Additite<and Crrntumin:rnts C,mmittee;-\Iini~try of ,3>;riculture. F'i%hi-rie: and Fixid; C.K.H.`1. Stationery Uftire, London. t1'EAST. R.C. (Editor) 197A. Handbi,ok of E'Bemi,try :md Phc`sics, 3Jth Edition. C.R.C. Pres-c, \\'est Palm Beach, Fbrida:
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392 SOURCE BOOK OF FLAVORS ORGANIC CHEMICALS USED IN FLAVORINGS AND FRAGRANCES 393 - -alstatua Physico-chemical characteriaticn Solubility Fln<h ' IOFI Puint 3 United C'lassi- g _ Y; _ Council Slatea 6ratiun 4,ilinR C-dd.ed y o( FDA +IOFI Pgint Sivhin>: nq~ FEMA Europe CIaRU- Positive (' Point Oa~~p.~n Chemical Name OtherNamee Nu. Na. ficatiun List ra i". (at mm Hg) 'C rul 3-Phe l l i ate 2897 419 172.515 Art VSI S 265 +1u0 ny propy prop on 2-( a-Phenylpn)pyl ). tetrahyd•ohuran 2898 489_ . _ 172.515 Art+ V-% _S-- a-Pinene 2902 2113 172-.515 NI In S In S 156-160 3.i/('1 r9=Pinene 2903 2114 172.515 NI In S VS1 S 164-169 31 2(10)-Pinen-3-ol Pinourveol 3587 172.515 In S S ri., 21i-. 51 tron, 210 5 Pinucarveol 3587 Y916a5 NI Piperidine He:ahydmpyridine 2908 675 172.515 NI S S 10r, 16 Piperine 1-Piparoylpipendine 2909 492 172.515 NI V SI S 128-129 Piperitenone--- . -172.51_5-NL - - Piperitenone oxide 3564 1i2:615 NI d-Piperitone p-Menth-d-an-3-one 2910 2052 172.515 NI In S '?a5-237 Piperonal Heliotropins 2911 104 182.60 NI In S SI 26:1 35.5-37 F('C E()A Piperunylacetate - Helirrtrapyla ceu- . 2912 2912 172.515 Art+ \'SI S 153-154 t14mm1 +100 Piperonyliw)butyrate 2913 305' 1:.515 Art+ VSI S +1n0 P::1'I'mnRn 172.515 Art . ....- _ Puly,utrhate 20 -.--Pnlyaxyetbylene(20)aorbitanmonolaurate . 2915 --172:515 Art S S FCC Polysorhate 60 Polyoxyathylene(20) sorbitanmonoa0eerate 2916 li^_.SIS Art S S In F('t' Polxaorbate 80 Polyoxyethylane(20)aorbitanmonoaleate 2917_ 172,515 Art S S Ft't' Putntuium acetate 2920 172.515 Art S S 292 +10t1 Potasvium aarbate Potasalum2,4-hexadienoate 2 21 1 Art S S +1U0 Ft't' I-Proline 2=Pyrrolidinearbo:yficacid 3319 4211 NI VS 81 In - 220-222 FCC (decomp,wa 1.2-Prupanedithiul _ _ 3520 Art+ 152 :15 1,3-Propanedithiol 3588 Art Prupanethiul .35gL_4213 172.515 NI VSI . S.-_ 6=6EL -.-211___.__ _ Propenylguaethul 2922 170 --L72:515 Art+ SI S S S 85-F(', +100 Fl'(- Propenyl tropjI disulfide 3227 4026 NI f'cupienaldehyde __ Propanal 2923 -9f1- 172.515_ Nt S ---S-----_- a8-49 -81 -9 ---_FCC- Propiunic acid Methylaceticadd 2924 3_ - NI S S 140-141 52 FCC 2-Prapionylpyrrule Ethyl2-pvrtolylketone 3614 172.515 Art 2Tropionylthiazole 1d2-9'hiasnlyU-1-prooanone 3611 -_ 172.515 Art - --- --- ~ Prupinjihenone 3469 599 NI 218 18 µM Propylacetate _. 2925 192 172.515 NI S S S S 96-102 ?ti Propylalcuhul 1-Propanol --_392A- 50 172.fi15 NI S S S 97.2 15 p`_Pr°pyJ-an'eule--_. Dihydroanethole - 2930 202('~_ 172.515 Art...._ c K'+ t•'0 A Prapylbenzoate _ 2931 677 1i2.515 NI In S `?:1U Propyl hutyrate 2934 266 172.515 NI VSI S 172-1Ja Propyl cinmmmate 2938 -~124 172.515 Art In S :83-28{ 13 +.1(10 Prupyl2;4-decadienoate 3648 - 172.515- -Art Propyl divulfide D't~ronyldiaalfide -. 3223 540 -172:515 NI VSI S 194 33 Prupyleneglycul 1-2-Dihydt'oxyprupana -- - --- - 2940 4212__ 1M2.t'i0____ . NI_ . 111 ]i7 In 187.3 +lu(1(U) F('(T Prnpyleneglycol alRinate_.--- Hydrosypropyla`inate 2941 _ 172.515-- Art 5 - - - +100 -FCO- ECZI6V46
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Patty-"s Indlustriat Hygiene and Toxicology~ THIIR'D REVISED E'DNf11ON' In, Three Volumes. Volume 11 OENERA,IL PR'INCIPL'ES Volumes 2A, 2B', and 2C TOkICOLOGIf' Volume 3' THEORY AND RATIONALE OF INDWSTRiAL HYGIENE PRACTICE Contributors B. D: Astill L. W. Hazletbn J. L. O'Donoghue R. R. Beard Gary, V. ICatz , V. , K. Rowe G. D~ DiVincenzo W. /. Krasavage H. E. Stokinger Derek Guest S. B., McCollister Robert 1. Weir Rolf H'artung, R'. Montgomery Mark A. Wolf (deceased) ~rE o2 G~ 1~. CLAyTaW- - E. CuJ*7Tar.(', IE DI TbR S- S -(,EARs (07 } A 14I71LEY-1INTERSCIENCE PWBLICATION'. /OiHN111YILEY & SONS NewYork • Chi¢hester • Brisbane • Toronto- Singapore 4F cfcf~' q
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1 I",1 '.. ". FA~~. 3852' V. K. ROWE AND, Mt. A. wOLF barbital, salicylic acid, and I-y-hexachlorocyclohexane were very poorly' absorbed! from solutions of the glycol. Polyethylene g)ycol E-300 (PEG3't10) and PEG-300Jinethylatedl spirits (PEG- IMS)i (6:1 v/v ratio of' PEG-300 to methyllatedl spirits (95 percent ethanol, 51 percent methanol)), have been reported to be superior to water when used as decontaminants of the skin of'ra'ts exposed to phenol, (248, 249)'. Other similarr studies using the skin of swine, believed' to be more si'nnil'ar to the skin of humans than is the skim, of rats, indicates that a water shower for 1!5 min is practically: equivalent to decontamination with PEGG300' or PEG-IMS. Both treatments were effective in reducing mortali'ty, skin~ injury, and' plasma concentration and, reten~tion time of absorbed phenol as compared to animals exposed to phenol but not decontaminated. These data plus the umiversai avail'ability of water ind'ieates that water is the decontaminant of choice (29)'. 6.4.13' Human Experience There are no reported human injuries or adverse effects from the handling of these poHyethylene giycols.. 6.5 Hygienic Standard's of' Pertnissilble' Exposure No hygienic standard is believedl necessary. 7 PRO'Pl'LENE GLYCOL;~ 1,2'-Propanediolt hAethyl l Ethylene Glycol; 1,2- Dihydroxypropane; CA5 No. 57=55'-6. ~'. a ~ CH-jCI-I0IH'CI!IlOH ~ 7.1 and Ittdttst'rial'Exposure Source Usrs , , ~ ; Propylene glycol generally is synthesized commercially by starting with propyl- ene, converting to the chllorohydrims and~ hydrolyzing to propylene oxide, whichh is then hydroNyzed!to propylene glycol. Itcania~lso be prepared by other methods (108).. Propylene glycoi is used in, antifreeze formulations, heat exchangers, andd brake andl hydraulic fluids; in the manufacture of resins, which accounts for aa largc portioni of its use„ polypropylene gl~cols, and propylene glycol ethers and. esters;~ as a soHvent in pharmaceuticals, foodls, cosmetiics, a'nd inks; as a plasticizer for resins and paper~ and as a humectant lin textiles, tobacco, and pet foods. Ilt is also used in the vapor form, as an ain sterilizer for hospitals and public buildings. Industrial exposures are from dlirecu contact, or from inhalation of vapors andl of mists where the material is heated' or violently agitatedL Other exposure is by ingestion resulting from its use in food's .nnd', drugs. I
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K. ROWE AND M. A. WOLF eve- ooorly absorbed iethylated spirits ('1''E(:- (95 percent ethanol, 5 to waterr when used as _'-f8„ 249). Other similar similar to the skin of : shower for 15 imin is 00 or PE(;-I141S. Both n injury, and plasma is compared to animads lata plus the universal iinant of choice (29). ,s fromi the handling of vcol; 1,2- w starting with propyl- propylene oxide, which )ared by other methods heat exchangers, and s; which accounts for a Nlene glycol ethers andd ind i'nks; as a plasticizer )acco; and pet foods. I'tt r hospiuals and public n inhalation of vapors itatedl. Other exposure E I (P rry s GILWCOLS 3853 7.2 Physical and Chemical Properties Propylene glycol is a colorless, ahmost odorless, slightly viscous liquid with, a slightly acridl taste. It imparts no odbr or taste of its own when used ini foodl colors and flavors. Additional physical' and chemical properties are given in Table 50:1. 7.3 Determination in the Atmosphere Thedetermination, of propyleneglycol, in air can beaccompli'shed by several of the methods noted under ethylene glycol, although it would seem unnecessary for industrial hygiene purposes. A methodl for detection of'propylene glycol in body fluids is described by Lehman andl Newman (11142). 7.4 Physiologic Response 7.4.1 Summary 7fhehazardsto, health, in theindlustriall handling and use of propylene glycolwoulld seem to be negligible. Its systemic toxicity is especially low and, since 1942, it has beeni consideredl a proper ingredient for pharmaceutical products (143). The Food and Drug Administration does not object to, its use in, food products or in cosmetics (144). The inhalation, of atmospheres containing, propylene glycol vapor presents no hazardl to healthi. Exposures created by operations producing hot vapors, or by high-speed mechanical action, in which ai fog of propyllenegllycol isproduced, have not been studied. However, it is difficult to 1 visualize how this condition could create a hazard, since the material is so extremely low in systemic toxicity. The toxicology of propylene glycol has - been reviewed extensively (20, 145, 146). 7.4':2' Single-Dose Oral The single-dose oral toxicity of propylene gllycoll has beeni studiedl by a number of investigators (142, 145, 1I47, 148, 139, 99, 17). The single-dose oral LDSO, values range, for rats, from 21.0 to 33.7 g/kg; for mice, from 23.9 to 31.8 g/kg; for guinea pigs, from 18.4' to 19,6 ' g/kg; for rabbits, from 15.7 to 19.2 g/kg; and for dogs, from 110 to 20' gLkg.. Laug et a1i (17) report observing miinimall kidney changes from large doses. From one-fourth to one-half of an oral dose given to rats, dogs, or human, beings appears unchanged in the urine within 241 hr (1142, 148„ 149, 1'50).. 7.4.1 Repeated-Oral Dose Seidenfeld, and Hanzlik (15'1) gave groups of rats dl-inking water containing 1.0„ 2.0, 5.0, 10.0, 25.0, and 50.01 percent propylene glycoll over a period of 140,
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days, Animals receiving water containing either 25.0 or 50 percent propylene glycol died in 69' days, whereas those receiving either 1.0, 2.0, 5'.0„ or 110.00 percent appeared normal ~ throughout the observation period. The averag!e daily intakes for the latter four groups were calculated tol be about 1.6; 3.7, 7:7, and 1I3.2'g/kg/day of'propylene glycol, respectively. Histopathologic examination of the tissues from~ these animals revealed no renai or other pathologic disturb. ances. Weatherby and H'aag (147) confirmed the fact that rats will tolerate 1'0;0 percent propylene glycol in the drinking water without physiologic impairment. Hanzlik and associates (148) found that rats could tolerate up to 30 mUkg daily of propylene glycol', when fed! in the diet over a 6'-month period. This is eqpivalent to 11.8 ' lb daily for a 70-kg person. Morris et, al. (19) fed rats ~ 2:4'5: and A. I 4.9 percent propylene glycol'in the diet, allowing, respectively, average daily ~, intakes of 0.9 to 1.77 mI/kg over a 24-month period without significant effect r on growth rate. Microscopic examination of the tissues revealed very slight liver d'amage, but, no renal pat'hology. Whiitllocketi al.(152)~ found that: a diet containing X percent of propyleneglycol, was not well tolerated'~ by young rats, and that producing females were unable to bring their young to weaning. Glycerin at 30.' percent' ini the diet wass well toleratedl Diets containing 40, 50; or 60 percent of propylene glycol were lethal!after a few days.Gaunt~ et al. (1I53) fed' both male and female rats, propylene glycol ini theirr diet at levels of 6;25~0~, 12,500 and' 50~,000'ppmforal period of 2' yea:rs. They found no signifi~cant ill effects based! upon mortality, body weight, foodl consumption, hematology, urinary cell' excretion; urine-concentrating ability off the kidneys, organ weights, or histopathology, including tumor incidence. They suggest thar; the acceptable daily intake for man would be 25' mglkg/day: (The 50;000, ppm level~is.equiWalent to 2.5 g/kg/day for the rat.) Van Winkle and Newman (155) showed that propylene glycol.,, when given in concenitrations of 5' or 10 percent in the drinking water of dogs: for 51 to 9 months, caused no adverse effects. Criteria employed: were liver function, kidney function, andl histopathologic examination of the visceral organs. Fmr- ther, they found no, alterations in the serum calcium levels of cats and dogs fedl large doses of propylene glycoL Weil et al. (154'), found that male and female dogs fed diets providing propylene glycol at a dose level'' of 2.0 g/kg, for 2 years were unaffected as judged by mortality, body weight change, dierutilization andiwateir consumption, histopathology, organ weights of liver,, kidney; and spleen, and measurement ~ of blood, urine, and biochemical parameters. At a daily dose of 5 g/kg, the dogs .~ ; gained more weight than~ the controls, especially during the early part of the experiment, owing, to the higher caloric intake. An increase in the rate of }~,y : erythrocyte hemolysis~~ andl a slight increase in total bilirubin was also~ noted. N ; Hemoglobin, packed' cell volume, and total', erythrocyte count were lowered ~W E slightly, whereas the incidence of ainisocytes; poikil'ocytes, and reticulocytes was increased, suggesting, that erythrocytes were being destroyed accompanied' by.
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:, ROIWVE AND Mt, A. WOLF .50 -cent propylene 1.0, _.0, 5,0, or 10.0 riod. TI 11e average dailk about 1.6, 3.7, 7.7, and hologic examination ol her pathologic disturb- at, rats will tolerate 10.0 ,hysiologic impairment. olerate up to 30, ml/kg )-month, period. This is . I! (19), fed rats 2.45 and pectively, averagedailj•e ithouti significant effect -evealed very slight liver !) percent of propylene ,roduciing females were percent in the diet was f propylene glycol' were ,-opylene glycol in their ,eriod of 2' years. They ty, body weight, food. -concentrating ability of tumor incidence. They be 25 mg/kg/day. (Thee at.) ne gl~ ..,t, when given in iter of dogs for 5 to 9 -d were liver function, he visceral organs. Fur- els of cats and dogsfed ,gs fed diets providing ,ars were unaffected' as and!water consumption, ,leen, and' measurement dose of 5 g/kg, the dogs ng the early part of the increase in the rate of -ilhrubin was also noted. vte count were lioweredd es, and reticulocytes was stroyed accompanied by T #Vy,5 Gt.t'COLS 3855 accelerated replacement from the bone marrow. This effect was not sufficient, however, even at tlie 20 percent dietary level to result in any irreversible changes and'i there was no evidence of damage to the bone marrow or spleen. They state that dogs fed propylene glycoll at approximately 8 percent in their diet (equivalent~ to 2' g/kg/day) can utiilize it as a carbohydrate energy source withi no adverse effects. The utilization of propylene glycoll as a source of carbohydrate energy inn animal feed has led to other dietary feeding studies involving, cattle, sheep„ chickens, and cats. lt is used in pet foods as a humectant as well as a source off energy. In lactating cattle, there is aitendency for the cow to develop hyperketosis which may be due to low carbohydrate stores in the body which are used to produce lactose excreted in the milk. Fisher and co-workers (156, 157), have summarizedi much of the work done to determine the usefulhess of propylene glycol as a dietary supplement to alleviate this condiitiion:. Fisher et all (156) reported on studies in lactatiing cows in which propylene glycoll was added to food' concentrates at levels of 3, 6, and 9 percent. The concentrate was fed' to cows for 8 weeks dhriing the early stages of lactation andl it was foundi that there was no consistent effect on feed intake, body-weightt change, or efficiency of ration utilization. Propylene glycol, at the 3 andl 6 percent levels, appeared to increase the yield of milk but, caused a slight decrease in milk fat andl an increase in milk lactose content. There was also a significant decrease in hyperketosisiin the propylene g)ycol tt-eated'' animalsaFcompared to the level in the control animals. Sauer et al. (157), in the study of 1I20cows, over a2'-yearperiodlinwh'cch propylene g)ycolwasaddred to thed'iet at 3 and 61 percent levels for 8' weekspostpamtunt, substantiated thesuitabiiityof propylene glycol as a food additive for such cattle. It depressed the blood' ketone and free fatty acids slightly below the control I cattle levell when the cows were not stressed by either high lactation yield or low concentrate food intake. However, if the cows were stressed by adverse environmental factors and slighitly reduced food concentrate intake, the addition of propylene glycol at 3 and 6 percent to the concentrate ration caused a significant reduction of blood ketones and plasma fatty acids and increased the bloodl glucose concentration.. They suggest that propylene glycol used as a, feed additive at 3 and 6 percent of the concentrate shouldl be desirable because of its ability to significantly decrease the incidence of clinical and subclinicall ketosis in cows during early lactation when, they are most susceptible to such metabolic disorder. Shiga et al. (158) fed male lambs propylene glycol at levels of 0.5 and 1'.0 g/ kg imithe feed every other day for 104 days. Neither level produced any adverse effects. They did increase the weight gain, especially in the early part of the experiment (about 30 days). Evaluation of the rumen liquor revealed an increase in propionate and total fatty acid concentrations. Tlie weight percentage of wooll, dressed carcass, andl red meat-fat ratios were also greater than those of the controls. Propylene glycol has been shown by short-term feeding; tests with chicks and. Q
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chickens ta be a suitable source of energy, the suggested 1'eveL acceptable being'• in the range of 2.5 to as much as 8 percent in their diet. However, most authors' feel that the levell should be no more than 2 to: 3 percent. Bailey et al. (159) feC4; chicks from I to 26 d'~aysof age wirhd'ietscontaining8 and 16 percentoE?~'propylene glycol!. The 8' percent 1'eveI was considered to cause no significant iJl effects as judged by live weight gain, food' consumption~ and'~ carcass analysis. The 16percent levelicausedgrowth depression and lower fat and higher protein contient~ in the carcass. Persons et al. (160) also fed chicks frotn day I for 3' weeks with levels of 5 and: 10 percent of propylene glycol, in the diet. Both levels showed adiverse effects, such as depressed body-weight gains at the 5 percent level~, and depressed body-weight gains and decreased food ef6ciEncy; but no mortali'ty at the 10' percent level. They also fed hens for two periods of 28 datys each with diets containing ProPylene glvcol at levels of 2:5~ andl 5'ff i percent. The 2.5 percent level'decreased food'consum tion owin to the hens 1 p g compensating for the change in energy intake, but there was no effect on egg production or general health. The 5 percent level caused decreasedl food andl energy intake and red''uced~ egg production. The authors suggest that a level of I 2.5 percent of propylene glycoll is ~ tolerated~ well by~ both ch~~icks and hens. I Based upon 21 to 28 day feediing studlies on chicks of diets containing 2.5, 5.0; and 1'0.0, percent ofpropyleneglycol; W!aldroupand, Bowen(161), . found, that chicks can utilize 5.0 percent of propylene glycol ini their diet without ill' effects. The 10 percent leveli caused depressed body-weight gaitts, reduced efficiency of feed utilization, diarrhea„and'.the development of deformed toes:. S'oshida et al. (34), also: found that chicks fed 5 percent of propylene glycol t in their diet for 27 days were without ill effects. Higher levelg,caused inferior i welll being and diarrhea. Harnisch (162)' feels that the no-effect level is in the range of 2 to 3' percent of propyiene glycol. This resulte& frorn~ his 8-week feeding studies on 4- to 5- week-oldbroilers,in whicLhe toundt tha~r aAiet containing 5 percent propylene glyeoldepressed' food intake atidl reduced feed conversioni ef'ficiency.Because of'the use of propylene gllycol as a huniect<1nt as well as a source of energy in prepared cat f'ood, a study (29) was conducted' in which groups of two male cats each were maintained for 94 days on diets containing various amounts of propylene glycol'. Two groups of two male cats,eacli served as controls. The average calculated doses of' propylene glycol consuwned', basedi on food intake and,body weigktts, were 0; 80, 443, 675, 1763, or 4"239' mg/kg/day: The priniary treatmenr-related effect was noted ii1 the red'blbod cells (RBC), which exhilbited. Heinz body formation. This effect ini the RBC was accompanied by increased . . amounts~~ of hemosideriim pigment in the Kup!'fer cells of the liver and retiicur 'J~ loendothelial cells of the spleen. 'P'he formation of Heinz lx>dies anK1', iincreased " ' hemosiderim occurred in a dose,related manner at doses of 675 mg/kg/dayy and~ 0 ~ higher.~ A daily~~ dose~~ le~~~el of 443~~ mg~/kg/day appeared to ~ cause avery sJi!ht ~ increase~ in Heina~ body ~ formFntion~ withouti detectabl~e~~ increasedi Ileinosiderin, (j presen ~ in the~ liver or spleen wlten compared tu the incidence ini the~ controls. 40'
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V: K. ROVVE'AfWD M. A. WOLF sted acceptable he iu y iet. Ih....ever, most al,thors -cenr. Bailey et al. (15!)) fc<1 ning 8' and 16 percent of d to cause no sis;iufaarnt ill ption, and carcass amah,•sis. -iwer fat and higher protein cl chicks froni day 1 for 3 ,e glycol' in the dict. l;oth ,c>dy-weight gains at the 5 decreased food eflliiaenc}•,, ed hens for two periods of ol' at levels of 2.5 and 5:00 umption owing to the hens there was no effect on egg caused decreased food and! -hors suggest that a level of fx)th chicks and hens. €ks of diets containing 2.5, ip and Bowen (161) found col' in their diet without ill • ody-weight gains, reduced •lopment of deformed toes. )ercent of pro'pylene glvcol gher levels caused inferior !he ra- Y of 2'to 3 percent feedif.b studies on 4~ to 5- aining 5 percent propylene version efficiency. -ctant as well' as a source of cted in, which groups of two containing various amounts ,tch served as controls. The med, based on food intake 39' mg/kg/day. The primary ells (RBC), which exhibited accompanied by increasedl ells of the liver and reticu, Heinz bodies and increased loses of 675 mg/kg/day and aredl to cause a very slight :ble increased hemosiderinn e incidence in the controls.. PK,~y.5. . GLYCOLS 3857 No treatment-relatedl ef fects ofi any type were observed in the group ingesting 80 mg/kg/day. Other hematolkagic parameters which were evaluated andl foundl tobeunaflfected by,any levell of treatment includedl paekedl cell volume, RBC count, hemogloliin„ RBC morphology to evaluate poNychromasia, RBC reticu- locyte count, R11iC osmotic fragility, methemol;lobini, total and' differential white blood'i celll counts, and light miicroscop~icexam~ination of tissue bonemarrow: In additiony serum clinical chemistry values of blood ureai nitrogen, glutamic pyruvic transamiinaseactivity; alkaline phosphatase activity, glutamic oxaloacetic transaminase activity, glucose concentration, andl total bilirubin as well as routine urinalysis were unaffected by treatment. The clinical' appearance andl demeanor, body weights, organ weights, gross pathology, andi histopathologyy of tissues other than liver andl spleen were unaffected by treatment at any of these levels of propylene glyccol.. It appears that the cat is much, more sensitive than other species to the formation and'/or retentiionof Heinz bodies. Even so, their presence in significant't numbers does not seem to adverselly affect the cats. 7.4.4 Injection Toxicity Table 50.8 gives the LD50 values by injection of various routes to a number of animal species. Brittain andl DParcy (165) foundl that when propylene glycol was injected' intravenously in rabbits, there were no effects on blood other than decreased clotting time, increased platelet count, and an increase in polymorphs accom- panied by a decrease in l~mphocytes. High doses in rats by intramuscular and subcutaneous injections resultedl in profound depression, analgesia, and coma (146). There was no anticholinergic effect in dogs but temporary increased1 urinary flow, peripherall vasodlilatation, and a temporary vasoconstriction of the spleen when propylene glycoli was injected intravenously (167). Repeated'subcutaneous: injection of propylenegliycoll to rats at a: dose of 2:5, ml/kg (2.6 g/kg) every other day for I month caused ani increase in oxygen consumption even though there was no kidney or liver histopathology found (167). 7.4.5 Eye Contact Propylene glycol' is not injurious to the eyes of'rabbits (39, 168) and has not caused any eye injury in human beings, nor would such be expected, but it may causetransitorystingiing, blepharospasmi,,and lacrimation (108, 139). 7.4.6 Skin Irritation and Absorption Propylene glycol generally produces no significant irritant action, upon the skini. Fromithe results of extensive studies by Warshaw andl Herrmann (169) on sorrte E
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Tab1e 5Q.8., Acute Toxicity of Propylene Glyco!'by Injection to Laboratory Anitmals Species Route of Adininistration 1'.Dya (g/kg) Ref6 Mouse Subcutaneous 19.2 146 15:5' 36: : Dntraperitoneal 9:73 1'46~ 12.9 139 1'3'.6' 36 6.8 163' 10!9 1'45 11.41 166 Intravenous 8.3' 146 7.6 139 Rat Subcutaneous 22:0, 25'.0 145 22.5; 21.7, 29.0 1'46'. Intrapcri't oneal 14.7; 13.5 146: Radiated PG 14,2'(13.7 mU'Itg)', 164 Unradiated PG 14.7 (14.2 m1/kg)' 164 Intraperitoneal 1'3.0' 1 "39' 16.8 (1&25mUkg) 99 Intravenous 12'.7(123 mUkg), 99i 6.2' 139 6:8 146 Intramuscular 14.0, 20:7 15.0; 13.0,.2'0:0 146 1145• Guihea pig, Subcutaneous 13.0L 15.5 146 Rabbit Intravenous 5.0 145' 6:5 146'. Dog Intramuscular Intravenous. 6.0 25'.9 145 146 866' human subjects with various d'ermatologie backgrounds, it appears that' propylene glycolmay cause primary sltim, irritatiion, in some people, possibly duee to dehydration, but the material does not appear to be a sensitizer. Because of the very low systemic toxicity of propylene glycol, no problemfrom percutaneous absorption can be anticipated'. Propylene glyco1' has been used: wid'ely in preparations for topical application and no evidonce of systemic injury to humans has been reported. These findings are substantiated by other workers (99, 1'68, 1170-1,75, 1,77). One of the many medicinaf uses of propyl'ene glycol is as a solvent in eardrops. Morizono and! Johnstone (176), found that a concentration of 10 percent, or more or propylene glycol! in Ringer's solution when instilled into the inner ear cavity of guimea pigs caused apparent irreversible deafness. 'Theyy recommend that iE propyl'ene glycol i's used in eardrops the concentration should be less than 10 percent. 87491241,
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:. ROWE AND M. A. WOLF Inject' - to Ref. 146 36 146 1391 36. 1163 1145 1166. 1146' 139 145 0 146' 146 kg) 164 kg) 164 139' IIlkg) 99 ~ l;g) 99 ; 139' I 14'6, ~ 146 10 145 146 ~45, 146 145 146 j ounds, it appears that : ne people, possiibly due a sensitizer. Because of ,lem from percutaneous been used' widely in of systemic injury to tiated by other workers col is as a solvent inn a concentration of 10' i when iinstilled into the ersible deafness. They ; rops the concentration 0 GLYCOLS 7.4.7 Vapor Inhalation auk~ 4° ti,~ LiZ, o- ~°~ tr" S rtj1,i : 3859 ~ Robertson et al. (1I19) exposed sizable groups of rats and monkeys f'or periods of 112to1'8monthstoatmospheressaturated wi'thi propylene glycol vapor and producedl no~iill effects. 1Hitmanibeiugs also, hiave~been exposedltosaturatedl and supersaturated atmospheres for prolonged periods in the air-sterilizationi pro- gram withouti adverse effect. The uptake of propylene glycol mist by humans was studied using a 10 percent solution in labeled deionized water nebulized into a mist tent ('178), Less than 5 percent of the mist entered tliebod'y; andlof~this90~ percent lodged in the nasopharynxan~dl rapidly dllsappearedl into the stomach. Wcry1'ittlewasfound in the llungs.. 7.4.8 Reproduction Guerrant et al. (179) checked' the reproduction capacity of'rats fed up to 30, percent of propylene glycol in their diets through sik generations. No adverse effects on reproduction were found when concentrations of propylene glycol in the diet were less than 7.5 percent. At higher levels the rats receiving the propylenegl'ycoll consumedd lessfood~ g{•ewsl'ower,had young, at an older age, produced smaller litters on the average, and weaned fewer young,than didl the control animals. At the 30 percent level, the females did not breed normally and when, they hadd young, they did not feedl them properly. They failed', to wean third generation young. Emmens (180) fed mice 0! 1 ml of a1 50 percent water solution of propylene glycol for several days prior to mating and' found that it reduced the mating to as little as 30 percent of normal, andl litters to 15' percent. The mice swell'ed visibly with intestinal I gases and then recovered'. 7.4.9 Teratogenicity . Gebhardt (181) found that 0.05 ml of propylene glycol was not teratogenic when injected into the yolk sac of chick embryos. &lowever, it caused a high mortality of the embryos whew injected into the air sac on, the fourth day of development and unilaterall tnicromelia in about 20 percent of the surviuors.. Wlaldroup and B'owen, (161) have reported that chicks fed high levels of propylene glycol ini their diets developedl a high incidence of toe deformities, 57' out of 168 chicks as compared to the control group, 9' out of 168. 7.4.1© Mutagenicity ll'Cennedy et al'. (182) studied the dominant lethall effects in mice treated withi propylene glycol intraperitoneally at a level of 110 mg/kg, The results suggest that it is nonmutagenic at this level. Pfeiffer andl Diunkelberg (247)', found! propylene glycol to, be inactive when tested against S, typhimuritum strains TA- 98, TA-100, TA-1535, and TA-11537. 87491242 0 , E
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P1qT7Y '5 7.4.111 Carcinogenicity v.~ K. ROWE ANtI M. A. WOLF ~ f Dewhurst et al. (183)' and'Baldwin et al. (1184)' iini studies on the carcinogenicity ~ of other chemicals used propylene gbycol as the solvent. .4s a result they tested ~ propylene glycol alone for carcinogenic activity. Dewhurst et al! (183) used! a# single injection of 0.2' ml whereas Baldlwin et al. (184) gave three to five ~ subcutaneous injectioms, amount not specified. In neither case were tumors observed over al period of about a year (1I84), or 2' years (183). Wallenious ~ and Lecholm (i1185) appliedl propylene glycol to the skin of rats three times a week for 14 months but found no tumor formation. Stenback and'. Shubik (186) conficmed! these fiindings when they applied propylene glycol at undiluted strengthl and as a 50 and 10 ' percent sollution in acetone to the skin of mice over their liifetime. Ptilol development of tumors has been reported in the lifetime dietary feeding, studi'es (1I9; 1'53, 1'54): In fact, Gaunt et all (1153) specifically states that no tumors were' found in the rats. Thus it' appears that propylene glycol is withoutt carcinogenic properties. 7:4:12' Metaliollism IRuddick (,145), in his review of the toxicity of'propylene glycoli summarized thee work done to establish its metabolism in the body. It is oxidized to lactic acid or pyruvic acid by two pathiways: These two metabolites are then, used by the body as a source of energy either by oxid'ation through the tricarboxylic aci', cycle or by generation of gIycogenrohrough the glycolytic pathway: The metabolic pathways are thought to be as shown in Figure 50:2: In ruminants, such as sheep and cattle, research has shown that the metabolism of propylene glycol is carried on to a large extent by the microbial floral in the rumen (187, 158, 156, 188) The metabolite is primarily propionate: In thee chick, excessive intake of propylene glycol results in its passagg to the cecum,, where it is metabolized by bacteria to propionaldehyde (1i90a).. 7:4'.13' Mode of', Action Browning (20) states that the studies on propylene glycol indicate that aboutt one-third is excreted' via the kidneys as a conjugate with glucuronic acid and the rest is metabolized or excreted in the urine unchanged. Tliis suggests that the organic injury and the centraF nervous system depressing action is probably due to the excessive presence of the prropylene glycol and not to its metabolites or its g#ucuronide. 7.4.14 Human Experience There has been no reported injury to humans that resulted from iindustrial use. Wowever, when used in large doses as a vehicle for repeated medication of a 8749i1 243 I
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GLYCOLS 38611 C. ROMW6 ANDi M. A. NfOitF on the carcinogenicity As a: resulti they testeci trst et al. (183) used a 14')'~ gave three to fiwe rher casewereuuuiors(:183)e t•col, to the skin of rats )rtnationa Stenback and ledl propylene glycoll in ~ in, acetone to the skiit. ~ IPhosphate. CH_;CHOHC;H2()'PO.:,l11 Propylcnu }llycul C;H'_,(;HOHK::HO. Lactaldchydc 1 •ifetime dietary feeding } xifically states that no ~ pylene glycol i's without glycol, summarized the oxidized to lactic acid s are then used by the ?tthe triicarboxylic acid + ;)athway. The metabolic ~ ,wn thatthe metabolisnim e tmtc, )al flora in the ~ rily piopionate. In, the ~ passage to the cecum, I ~ 1190a).~ col' indicate that about th glucuronic acid and'd ged. This suggests that •ssing,action is probably td i not to its metabolfites, ted from iindustrial, use. peated medication of a, CH',C110HC:HlOH phosph:uc ~ H.,O PO i H,_, Acetol pho.sphate I C H:,(;O'C: HO Methyl glyoxal CHyCHOI-iCH(OI-1)OPO_,H2 CHyCH:OHCOOH. tactafdehydephosphate Lactic acid CH,wCI-1OHCOOP%1H2 C1-1yCOCOOH Lactyl I phosphate Pyruvic acid CI-I.,CHOHCOOH Lactic acid Figure 511.2' Metabolic pathways of propylene Rlycoll 15-mo-oldl youngster,it caused' adverse signs characterized by hypogl~ycemia and central nervous system depression. Recovery was prompt upon cessation of treatment (190b)., This observation would seem to have no : significance as, far as the hazard from iindustrial exposure is concerned. 7:4.,15 Pharmacologyr Propylene glycol is, so low in pharmacological activity that very large doses can be given intravenously, provid'ed' it is given sloM1Vly. Rapid ad!miitistration causes, death. The material' appears to, have a sedative-type of effect, and is glycogenic (14'8).. 7.5 Hygienie Standards of Pertmissilhi6 Exposure 1Vone appear to ibe necessary. S'749124'4 0
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KIRK:-OTHIMER' ENCYCLOPEDIA OF CHEMICAL TECHNOLOGY THIRD EDITION I 19 Cb' A WA.ffXaNTERSCIENCE PUBUCATION I ~ Jbhin WJ'1ley & Sons ~ NEW' xORK • pHC:HiESTER • BRL4BANE • TORONTO, IDA C11
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94 ANTIFREEZES AND DEICING F4WID6 . !:IRK - r,TRrnEe, VOI.. 3 . base materials can be found': in standard reference books (48): The biggest hazard'': with~ ethylene glycol antifreezes is oral ingestion, particularly by children: The acute toxicity is low to moderate based' on tests with several animal species. For humans, a lethall dose is about 1.4 g/kg or 1001 mL for an adult. There appears to be little hazard' t'oo contact with skin or eyes if the exposure is not extensive or prolonged: Repeated or prolonged exposure to mists or, hheated vapors shoul'd' be avoided': but at ambient temperature the vapor pressure of ethylene glycol is very low. Propylene glycol has a very low singl'e dose oral toxicity, the lethal dose for humans is estimated to~be greater than~a liter. Skin contact produces essentially no effect short term although dermal''l studies with, humans indiicate primary irritation can occur withi some individuals, possibly due to dehydration. Skin sensitization, however, is not ini evidence and skin absorption is not likely. Eye contact does not result in irritation. Inhaiation exposure to vapors'anid mists appears to cause no adverse effects. Both ethylene and! propylene glycol!are apt to enter the water environment after use. They have high solub'llity and low vapor pressure. They have low toxicity to fi'sh,, animal wildlife, plant life, and microorganisms. Biodegradation is fairly rapid andi complete. The ehief'consideration is to avoid! a, local high concentration that couldl overload the mechanisms'of'd.isposall in the environment. BIBLIOGRAPHI' t 9: R: C: Weast and co-ed§., Handbook of Chemistry and Physics„56th edl, The Chemical ~ Rubber Co., Cleveland'4 Ohio, 1967-1'968: 1',0: J1 A. Dean, ed., Lange's Handbook of Chemistry, 11th ed.. McGraw-Hill!, Book Co., Ihc., New York„ 1961. 1',1., Physical'Properties, Synthetic Organic Chemicals, bulletin Union Carbide Chemicals Co., New York,, 1961. i 12' PhysicatProperties of Glycerine and its:Solutions, bulletin, Glycerine Producers Association. New York. ( . ~'7 1'3. DOtit"TP/ERM'209 Coolant, bull'etin, The Dow ChemicallCo., Midland„Mich.,,1,9'71., ! '~~ 14. AMBITROL Engine Coolants, The Dow Chemical,Co., Midland, Mich., 1976. ~ 1',5., AnnualBnok of ASTM'Standards, Part30,,American Society fcirTestingend Materials, Philadelphia ~ 1 6 - Pa. 16. E1,Beynon and co-workers, Material Research and Standards, American Society for Testing and ~ Materials, Philadelphia, Pa.,,June 1970, p. 33. ~, 17: H. C. Duus, E. H. Kellner; andllH. M. Cadot,,lnd. Eng. Chem. 30,143 (1938). 181 1 E: Miller andl'h. Alfrey, Jn, The Effect of Ethylene G.lycoGand M'ethoxypropanol Based Cuolant's "Antifreezes" in ECT 1st ed., Vol. 2, pp. 3'7=50a by D. G. Zink, U.S; Industrial'Chemicals, Inc.; "Antifreezes and' Deicing Fluids"'in ECT; 2nd ed., VoL 2', pp. 540-561, by R. W. Kallgren, The Dow Chemical Compa- ny: 1. Frank Howard and co-workers, Automotive Antifreezes; Mational, Bureau of Standards Circular 576, U.S'. Department af'Commerce, UIS. Government Printing OfSce; Washington,,D.C:, July25, 1956. 2:, Maintenance of Automotive Engine CoolingSystems, Society'of'Automotiae Engineers (SAE):Booklet TR 40, Warrendale, Pa. 3. Summary of Antifreeze Sales for 1959 and 1960, Chemical Specialties Manufaeturers Association, Bulletin PNo. 173:614 May 16,196'1. 4: G: A. Paul, The Effect of Selected'Coolant5 on M'etal Temperatures in a Rotary Engine:, Paper 741091, SAE Automotiue'EnginRering M'eeting, Toronto, Canada, October 21-25; 1974.' 5. G. 0. Curme, Sr.,,and' F. Johnston, Glycols, Reinhold,Publishing Corp., New York,,1952; p. 170. 6:: Dow Pr'opylene Glycol, USP, bulletin, The Dow Chemical Co., Midl'and, Mich., 1974. 7: Properties and Uses of Glycol, bulletin, The Dow Chemical Co.,,M',idland„Mich:, 1974. 8: Glycols, bulletin„Uhiion Carbide Chemicals Co~, Division of Union Carbide Corp., New York, 1958. on Elastomers, Paper 680496, Mid-year Meeting, Detroit. Mich., May'20-2-1,,19bdii 19: D. Caplan and'M:,Cohen, Corrosion (Houston) 9, 284'(1953): `
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K') RKc)7AfA'( P- Vol. 11 GL1'QOLS (ETHn'LEfWE AND PROPYLENE) 9511 Table 11. Toxicological Properties of Triethylene Glycol Derivatives •' )erivative Sinl;leoral LUra, rats', g/kg Sinl;leskin penetratiiin L1Dr, rabhits', mL/kg 5inglt+ inhalation" c mcentkated vapors, rals P>•imarv skin iiritation°', rabbits Eye injury, ralibitti tbl on nel Ji ena methyl 11181i 7:1 8'h killed I0 uf G trace none ethyl 1013 8 none tracee n-IiutSd 6.74 3!59 8 h killed 0:of6 trace moderate IJlalhwx dimethyl 2.5-5 none none lJiiut trs diacetate 25.28' 1'6I 8 h killed 0vd0' none trace ' Ref:c. 19;,2'1-22: b The term LD;,o refers to that quantity of chemicaLthat kills 50% of dosed animals within 14!d.. Single skin penetration, refers to a 24-h, covered skin contact with the liquid' chemical. ° Single inhalation refers to the eontinuous breathing of certain concentrations af'chemicalfi for the stated period. ' Primary irritation referstao the skin response 24 h following application of 0.01 mL amounts to uncovered skin. / Eye injury refers to surface damage produced by the liquid chemical. lower hygroscopicity (1)s Physical properties are listed in~ Table I and toxicological properties in Table 2. Tetraethylene glycoll is a coproduct of ethylene glycol produced by: ethylene oxide hydrolysis. Like: triethylene glycol„ tetraethylene glycol is also produced!commercially by the direct reaction of ethylene oxide with the lower glycols: The price for tankcar quantities of tetraethylene glycol was $1L0'1/kg iin early 1979. Tetraethylene glycol is usedlto separate aromatic from nonaromatic hydrocarbons by selective extraction. The criticallsoliutiontemperature of a: binary, system consist'ing, of a given alkyl substitutedlaromatic hydrocarbon andltet'raethylene glycol is'lower than the critical solution temperatures of the same hydrocarbon with the lower polyglycols. Therefore, at a given temperature, tetraethylene glycol tends to extract the higher molecular weight alkylbenzenes more efficientlly: Other uses are similar to those of'triethylene glycol.. YmRylene Glycol 1,2-Propylene glycol is a clear, viscous, colorlessliq,uid t'hat', is practicallyodorless and has a slight' characteristic taste. Although more volatile than ethylene.glycol, propylene glycol is about three times as viscous at room temperature:. It has a very low, order of toxicit!y and is highly hygroscopic. Physical properties of high-purity material are listedinTable 12:. Propylene glyeol'!from propylene oxide was discovered in ~ 1859 by VKurtz (30)i It was of little commercial importance, however, until 1931 when it was first producedl by the hydrolysis of propylene oxide (qN)!. Today the hydrolysis is carried out under pressure and at high temperature without'catalyst (eq. 19)'.: CHs CHIu I uP 'p I CH - 'H Hi ~ ~O -i HOCHCHiOH + dipropylene glycol 200e propylene + higher adducts propylene glycoll oxide (19) ~
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952 GLlf COLS (ETHYLENE AND PROPYLEPWE)~ K i P t C17NMt~ f-- Table 12.', Physical Constants of Propylene GlyEol' Property Value mp, °C -60b' bpat 101.3 kPa°, °C, 187:3' densityat 20°C, g/om~ 1.0362' surface tension at 20°C, mIV/m (= dyn/cm) 35.6 refractive index, nff 1.4'326' vapor pressure at20PC„kPa`' <1.3 specific heat, J/(g'C) d as liquid; 20°C 2.481 as idoal gas, 25°C' 1.611 heat of vaporization at 101.3 kPaf„kJ/mold 52.296 heat of combustion at 25°C, kJ!/moh 1824.0 critical conatants pressure, kPaQ1 6100.27 temperature, °C 352' volume;, L/mol' 0:237' compression factors Z, 0:278'' viscosity,, mPa-s'(= cP)) at q°'C 255.4 ' at 204C 60.5 at 4'0"C 19.45 ° Ref: 29. a'Sets to glass. ~' To convert kPa to mm I-Ig, multiply by 7:5:. a Tb convert J to: cal, divida by 41184! The proportion of products is controlled by the mole ratio of water to propylene oxide (see below for i'somer, distribution in dipropylene glycol). Higher hydrolysis ratios irlerease' the yield of propylene glycol but! also the costs of purification:, A ratio of 15' provides a product mix of'85% propylene glycol, 13%a dipropyle'ne glycol, and 1.5% higher adducts. Although propylene glycol has a secondary hydroxyl group, its chemistry parallels Table 13. United St'ates Producers of' Propylene Glycols Producer Location Dow Chemical U.S.A. Olin, Corporation Oxirane Corporation Jefferson,Chemical Company, Inc.° Union Carbide Corporation Total Annual capacity, thousand metric tons Propylene Dipropylene glycol° glycolh Freeport, Tex. 11:3.4 11.8 Plaquemine, La,, 68 5 W Brandenburg,lCy: 20.4 1'.8 ~j Bayport, Tex. 1113.4 8.2 6.1 Port l+feohes, Tex. 18.11 3.2 Institute and South, Charleston, 45.4 3.6 W. Va. 378.7 33.6 ~ °'IRef. 14. a Reft 15'., °' A wholly owned subsidiary of Texaco, Inc.
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k i,ar-601W rvlene ozide. Ilysis 0s ~ ratio o11T:, .1, andl rrv parall'els Wol. 11 GLYCOLS (ffTIIHYLENE AND PROPYLENE)' 953' Table 14. Propylene Glycol U§esa' Use Percent polvester resins 45 pet food 12' tobacco humectant 7' cellophane 7' t food and pharmaceuticals 11 miscellaneous 8' € exports 12' Total 100 , ° Ref. 14. that of'etlhylene glycol! Propylene glycol is produced in the United States by five companies having a combined annual nameplate capacity of about 388' X 103 t (see Table 13): Uses. Propylene glycol has a variety'of applications (see Table 14). In, the food industry it is used as a solvent, humectant, and preservative, in the manufacture of' products that come in contact with food' such as plasticizers for food wraps, as a: solvent for food processing, and as lubricant for food machinery. It is a softening agent,, spreader, emollient, intermediate, drug vehicle, and preservatrve in the preparation of cosmetics and pharmaceuticals. Aqueous solutions are effective antifreeze mixtures (see Pig, 1)i and are preferred' in refrigeration (qv) units in breweriies; dairies and packing houses, where a coolantt or heat-transfer solution of low toxicity is important (see Antifreezes). These aqueous solutions are inhibited to prevent rust and corrosioni Derivatives. The dleriivatives of propylene glycol are prepared by'met'hods anal- ogous to those for ethylene glycol derivatives. The base .catalyzed reaction of propylene oxide with alcohols gives predominantly primary: monoalkyl, ether, CH3CHOHCH2OIL', and slma111'amounts of secondary ether, CHsCHOIi;'CH~OH. Acid catalysis increases the ratio of secondary to primary ethers.1VPonoalkylethers can also be prepared'~ without catalyst under the proper conditions of temperature and pressure.. Tlie.monoalkyl ethers of propyllene glycol are exeellentsolvents for a wide variety of organic materials. The lower alkyl ethers are completely'miscible with water at room temperature and are soluble in ~some hydrocartions: Properties for a number of these materials are list'ed in Table 154 The ethers and esters of propylene glycol are prepared from the glycol by: con- ventional methods: Propylene glycol yields isomeric mixtures of esters because it contains both primary and': secondary hydroxyl groups. Monoesterification occurs usually at the primary hydroxyl group. Fatty acid esters, such as the dioleate:andlthe monohydroxystearate„are used iin,ointments, drug,creams„cosmetics (qv), and sur- factants (qv):, Dipropylene ClKcoll Dipropylene glycol is a coproduct of propylene glycol in, the hydrolysis of pro- pylene oxide (eq. 19); the approximate isomer distribution is: dar HOCH_.CHOCHCH_>OH CHyCHCHzOCH:.CHCH; CHyCHCHzOCHCH,OH I I I I I II CH,1 , CH3 OH OH OH CH3. 4% [10Q6-61-2] 4'396 [11A-9B-5] 53°b [106-62-7]'
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Table 1 (contlnued) ~ Solventt CAS Registry No. Common name (trade name) ethylene glycol [11J-15-9J 2'-ethoxyethyliacetate monoethyl etherr (Cellosolve acetate acetate) ethylene glycol', dim th l th l 1110-71-41 (dimethyl Cellosolve) e y e er ethylene glycol, [111-76-2] 2.butoxyethanol monobutyl ether (butyl Cpllosolve diethylene glycol [111 -90-0[ (C>tirbitol) monoethyl ether ethylene glycol [122-99-61 (butyl Carbitol), h l th monop eny e er ethylene glycol [112-07-2] (butyllCellosolve), monobutyliether acetate) acetate diethylene glycol, [112-15-2J (Carbitol acetate), monoeth_vl, ether acetate diethylene glycol [1'1'2-34-5] I (butyl ethyl Cello- monobutyl ether solve) propylene glycol [770-3.5-4J1 (Polysolve PM) h l th monop eny ,e er diethylene,glycolI [124'-17-4'](butylCarbitol mono-sec-butyl I acetate) ether acetate Ketoness acetone [67-64-1] 2'-propanone,di- methyl ketone methyl ethyl ketone (M'EKJ, mesityl loxide cyclohexanone methyl n-buty[ ketone (MBK) methyl isobutyl ketone diacetone alcohol l methyllamyl ketone methyl isoamyl ketone diisobutyl ketone isophorone Solubility Empirical KB parameter E',, formuhi valhe","' (J/mx) ttt X 10-3° C6H1~O;i 4.2 CrHI,bO2 C6H,,4O2 4.6' CsH140k4 4.98' CaHtoOi? CaHtr.Oa CwHi6O. CaHIeOs C9H,101. 4-6 4.93 CioHnsOs 4!1 C3H'6O' 4.8' [78-9:1-31, 2-butanone C4kI80' 4.51 [Z41-79-7], 4-methyl-3-penten- CsHtu0' 4.4 2-one. [108-94-11 cyclohexylketone C6Hto0 4.8 [591-78-67] 2-hexanone C5Hit0 4'.O [108-10-1 ] C6H l2O 4.1 [1'23-42-2J diacetone, 4- CeHi202 4.5 hydroxy- 4 -methyl-2! penta- none (110-43.0] 2-heptanone C7H40 4.1 [110-12::3J C7H,y0 4! 1 [106-83+8] C8Htl0 3.8 [78-59-1'[ 3;5;5*trimethyl-2-cy- C8H140 4.4 clohexen.l-one (1 thers ethylene glycol [u07-21-1'J propylene glycol [57-55-6] diethylene glycot [ 111-4ti-6[, acetonitrile [75'-05-8J methyl cyanide 384 C,Hi;Oq 7:13' . CalieOz 6!15 CaH iuO3 , 5.90 C,IH;,fV 5.80 - W:: (at N othe! In w 22.9 m m 22' m m. 6.5 m 1.7 m 0.4 &5. 0.05 1.2.
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kr 1°E! - l/DC• Water aolubilitw (at 25°C, except! where noted otherwir.e)l wt!%d,°' In water Water in Vapem pressureg Specific Refrractive Boiling range at 25"C except where grauitv' (at 20p'C index) (aU 20'C. Azeo- at 101.3 kPa noted except where except where Freezing trope; (= I atm), otherwise)',. notedl noted point', wt%/°C' °C!` kF'ah otherwise) otherwise) °C 2'Z'.9' 6'.5' 44:4/97,5 156 0.145 0.9730 1.4u2:~,,.; -62 81 6.420 0.8692 -6(l, 20.8/98:8' 170 0:1,1. 0j90075 1.4198 W none 202' 0:017 0.9885 1>4273 qq 215 110a 1.1 1.6' 192 0:9424I -64 none 217 0.013 1.0096 1.4213 -25 ~ 231 0.003 0'.9553 -68 6.5 3.7 247, 0:0013' 0.981 -32 m none 56 24.3 0.78998 1.35868 8' -95 24•,ii 1020 88.7/73 79 12 0j8049 1 1.3788 -8-1 130 1.3 0,8539; -59 2.3•~u 8.020, 45/96 156 0.64 0.9509915; 1'~.45097' -32' 1.4 127 113;0 0.830o -5-4 1.7 ' 1.9 75.7/87:9 1161 2.7 0:8008 1.3957 -84 , 15.7/99:5: 168I 0.23 0.9387 1.4235' -44! 0.4 1.5 150 1.18 0.'817 1.4110. 6.5 1.2 144! 0~8132' -74 0.05 0.8 166! 0.81 1.4230 -47 1.2' 4.3' 215-220 0!922 ~ none 197 0:016' 1.1135 1.4318 -1:; m none 187 0.017 1.0362 1.4329 -60 none 244 <0.0013 1.1164, 1.4475: -6;5. 84.2/76.7 82 111.8 0.7822 111.34411 -44 385'
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flavor and Fragrance Matea-nals-1981 Worldwide reference list of materials used in compoun .ding flavors and fragrauees Comoed by the Chemical Sources Association, '"'a.'s" gtou, D. C. z?t-k 3' (, A1lured Publ.ii . ~shing Corporation, Wheaton, "~~ nois, USA
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Intraduction to RamQr and Fragral+ce Materials -1981 This: is the thirdi compilation of this series,'-2 and by fan the most ambitious initerms of' the amount of' information gathered into one volume. In, addition to the extensive list off flavor substances listed in the 1979 edition; this edition includes over 1000 fragrance substances. A most important addition is the suppliers of, these materials, accomplished through the efforts of' the Chemical Sources Association (CSA), (see the report beginning on page 00). Th& CSA, has been very active in finding and developing sources for flavor and fragrance materials for severall years; and! this, volume puts their extensive re- sources of companies and products at the disposal of the worldwide industry. This list of' flavor substances is based on, the computer files of the Flavor & Extract Manufacturers Association (FEMA), which in turn is based on the FEM'A GRAS lists," with additions from other FEMA and'l Food and! Drug Administration list . Additional'flavor substances were added from the records of, CSA which are principaliy natural juices, herbs and extracts which are legally considered foods rather than flavor materi- als andi therefore, do not appear on the above lists. The fragrance materials were compiled from the: list of materials which the Research Institute of Fragrances Materials has investigated for their safety in fragrance use, plrJs the list of substances, for which there are published EC)A/FMA standards, plus addi- tional materials which have: been suggested by several fragrance companies and sup* pliers of fragrance materials. An important problem when dealing with a combined' list of flavor and fragrance rma+- terials is the different terms that are often used for the same materials. This was a problem with all ot thes lists checked for this, volume. While we have tried to, find the identity of each material, it is certainithat users of, this volume will find many instances of different materials under the same name: It is even more certain thatt the same rnaterial, will appear more than once!under, the various names by whichiitl is known. References are given after each principle name, providing the following information, on,each applicable materiai: The first number foilowingithe principal name is that assigned the substance in one of! the ten FEMA GRAS lists: fVhmbers 2001-3124', GRAS 3; 3125-3249, GRAS 4;, 3250- 3325, GRAS' 5; 3326-3390, GRAS 6; 3391-3423!, GRAS 7; 3424-3444„ GRAS 8; 3445- 3475, GRAS 9; 3476'-3525, GRAS' 10; 3526-3596, GRAS' 11; and 3597'-3650', G'RAS.12. A separate list of all of these FEMA substances and their synonyms in numerical order begins on page 179. The secondrn,mLer following each principal name refers to the section oft the 21 CFR where the substance is listed. The third'! number refers to the number by which the substance is listed in the publi- cation "Matural' Flavouring Substances, Their Sources, and Added. Artificial Flevouring Flavor & Fragrance Matariatsi - 19811 - Allllired IP'ublisthi'ngi
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Substances" of the Council of Europe (CoE)'.61 A revised Council of Europe publication appeared at the end of' 1981, but too late to include its data in, this volume. There are some substances in the CoE list that are not' included here because there is not evi- dence that these are being used inithe United States; The fourth number indicates the class of' flavouring substances. The division of flavouring substances into three categories was proposed by the International Organi- zation of the Flavor Industry (IOFI)¢' and has beeni adoptedi by the FAO/1MHO Food Standardl Programme, the Codex Alimentarius Commission. The official definitions for the three classes of flavouring, substances, indicated by the numbers 1, 2' or 3' read as foilows'-8 Natural' Flavours and Natural Flavouring Substances: For the purpose of the Codex. Alimentarius, "natural flavours" and' "naturall flavouring substances" are preparations and singJe substances, respectively, acceptable for human consumption, obtained ex- clusively by physical processes from vegetable, sometimes animall raw materials either in their natural state or processed, for human consumption. Nature-Identical Flavouring Substances: For the purpose of the Codex Alimentarius, "nature-identicaP flavouring substances" are substances chemically isolatedl from aromatic raw materials or obtained synthetically; they are chemically identical to sub- stances present in natural products intended for human consumption, either processedd or not. Artificial Flavouring Substances: For the purpose of the Codex Alimentarius; "artificial' flavouring, substances" are those substances which have not yet beeni identified in nat- ural products intended for human, consumption, either processedlor not. The fifth number refers to, one of the six appendices, numbers 1 throughi 6, of the "Report on Review of Flavouringi in Food,"9 published by the Ministry of Agriculture, Fisheries and Food of the Unitedi Kingdom, (UK list). Again, not all I substances on the UK list are included here. The sixt,h c.nhimnlis used for an alphanumeric code to the Scientific Literature Review (SLR) in which the substance is reviewed. This code refers primarily to SLRs produced by FEMA under contract to the FDA. The titles of' these SLRs together with the order number and a price code are listed below. These SLRs and their supplements are all- available either bound or on microfiche fromi the National Technical Information Seo- vices (NTIS) in Springfield, Virginia. The exact price can be obtained from NTIS by giv- ing theprice~ code: It should! be mentioned that theSLR' supplements refer often totheo original and should not' be used without it In some cases the ~ supplements are included' with the original as noted. These FEMA SLRs cover groups of~ substances with, related chemical structures and therefore; presumably, related metabolic andi toxicologic properties. For example; SLR'. Al covers 56 substances with similar functionality. An additional 6' compounds in this: chemicaliclass are covered inisupplements to SLR Al. The date the SLR'was submittedl to FDA is also included on the list. Where the SLRI reference is simply "PB;"'this indicates that the material was reviewed in a report not prepared by FEMA. In these cases, the order number and price code can be obtained from FDA. There are a few substances which are covered both in a FEM'A SLR and in a report not, prepared by FEM'A. In these cases, the only reference given i is to the FEMA publication which, in turn, gives reference to the other review. VI Flavor & Fragrance Mlatbrials - 1981 1 -/k0ured IPublisFtaingi
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The seventhi column gives the Chemical Abstracts Service (CAS) number for the sub- stance. A number is assigned by CAS'to each material which appears in the literature, and this number is becoming1widely usedlas prime identification. The eighthi column indicates if the substance appears among the monographs pub- lished in the Third Edition of the Food Chemicals Codex.'o The ninth colum~ indicates if the substance has a monograph in the series published by the Research Institute for Fragrance Materials:"' The tenth column, indicates if there is a standard for the material publishedl by the Es- sential Oil Association of the U!.S. (now known as the Fragrance Materials Association13' The eleventh column indicates if'that material is mentioned in the Guidelines pub- lished by the International Fragrance Association (IFRA). These guidelines give the rec- ommendations of IFRA for the safe use of' fragrance materials, based on the latest re- searchi information, available from, publishedi and unpublished sources, worldwide, of adverse reactions to the use of' fragrance materials. The recommendations sometimes recommend that a particular material not be used in fragrances, but more often recom- mends that ai material not be used above a given level, or that a specially processed form oflthe material be used that has proven to be safe. Finally the suppliers of both flavor and fragrance materials have been listed. The in- formation under "sources" in this volume has been taken from CSA publications and files, as well as from information sent to us specificalliy for this publication. Our, aim is to provide a full and complete source listing of'all these materials worldwide. All the infor, mation that our readers may be able to contribute will be greatly appreciated. This publication is intended to aict in the search for a particular substance in one of the resources mentioned above. Although a reasonable effort was made to find all l list- ings, it is, probable that some were missed. Accurate cross-referencing was difficult.. This is especially true of' the botanicals. Here it was assumed that where the species were the same oni two or more referenced lists, the substance was the same unless it was clearly differentiated by refr;rence to a particular part of the plant, i.e., roots on one list andi leaves on another. It is important, therefore, to emphasize that if~ accuracy is desired, the originall list should be consultedl for verification. If you find any errors in this Edition, it would be greatly appreciatedl if you, could let us know so corrections can be made in the Fourth Editiom References 11. Fordi R: A. and Cramer, G. M., Reference list of flavoringi substances ini use in the United States. Perf. Flavorist 2(1); 1, 1977 2. Ford; R. A., Flavor Maferials 1979, Allured Publishing Corporation, Wheaton, Illinois, USA 3. Hall, R: L., and Oser, B, L., Recent progress in the consideration of'flavoringi ingre- dients under the Food Additives Amendment. FEMA GRAS Substances 3. Food' Technol.' 19(2), Part 2, 15 1, 1965; 4. Food Technol. 24(5), 25, 1970 4. Oser, B. L.,, and Hall~ R. L., Recent progress in the consideration of flavoringi ingre- dients under the Food Additives Amendment. FEM'A GRAS Substances 5. Food Technol. 26(5), 35, 1972: 5. Oser, B: L, and Fordl R• A., Recent progress in the consideration of flavoringi ingre- dients under the Food Additives Amendnnent: FEMA GRAS' Substances 6. Food Flavor & Fragrance Materials - 1981, - I111ured Publishing vlil
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Technol. 17(1), 64, 1973;, FEMA GRAS Substances 7. Food Technol. 27(11), 56, 1973; FEMA GRAS'. Substances 8. Food Technol.' 28(9), 76,, 1974;, FEMA GRAS Substances 9: Food Technol. 29(9), 70, 1975; FEMA GRAS Substances 10. Food Technol. 31(1); 65, 1977; FEMA GRAS Substances 11. Food Technol. 32(2); 60, 1978; FEMA GRAS Substances 12. Food Technol: 33(7):, 65, 1979 6: Council of Europe, Natural Flavouring Substances, Their Sources and Addedl Sub- stances, Strasbourg, 1973, p. 463 7. Grundschober, F.; Hail„ R. L.; Stofberg, J.; and Vodoz, C. A., Survey of' Worldvvide. Use Levels of'Artificial Flavouring Substances, Flavours, 1975, pp. 223!-230. 8: Guide to the Safe Use of Food Additives, FAO, CAC/FAL 5-1979; p. 6 9: Ministry of Agriculture, Fisheries and Food; Food Additives and Contarninant's Committee, Rr?port on the Review of Flavourings in Food, Her Majesty's Stationary Office, London, 1976', p: 1901 10. Food Chemicals Codex, National: Acaderny Press, 21011 Constitution Avenue, NW, Washington, DC 20418', 1981 111. Researchi Institute for Fragrance Materials, 375 Sylvan Avenue„ Englewood Cliffs, NJ 07632, USA 12. Fragrance Materials Association of the United States, 900 17thi Street, NW, Washington, DC 20006 13. International Fragrance Association„ 8 rue Charles-Hubert, CH-12051 Geneva, Swit- zerland. viiil Flavor & Fragrance Materials - 1981 - Allured Publishing
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FEMA FD:A CoE Nat GB' SLR CAS' FCC RIIFM EOA IFR'A. 2'-Propionylpyrrolie 3614! 2' D3 1073-26-3 2'-Prop ionylthiiazolic 3611 2' ©16' 43039-98-1 ,piiophenone 3469' 599 2' C 14 93-55-0 Source: SKK H&R'R n-Propyl acetal' Source: GIV' Propyl acetate 2925 172.515 192 2' 5 1 09-60-4. x GRDNi S ource: Propylacetic acid See Valeric acid ,8-Propylacroleini See 2-Hexenal ,8-Propylacrylic acid See trans-2'-Hexenoic acid' 3-Propylacrylic acid See trans-2-Hexenoic acid Propyl alcoholl 292~8172:5'15 50 25 IVII1i 71-23-8 I Source: CLNS ESTM sec-Propyl alcohol See Isopropyl alcoholl PropyU aldehyde See Propionaldehyde 3-Propylallyl aUcohol See 2-Hexen-l-oll p-Propyl anisole 2930 172:5'15 202'6 3 6 C23' 104-45-0 X' Source: FRUT GIV FDO n-Propyl benzenecarboxylate See Propyll benzoate Propyt benzoate 2931 1172'5'115 677 2 5 C9 2315-68-6 p-iso-Propylbenzyl alcohol See p-Isopropylbenzyl alcohol n-Propyl benzyl carbinol See a-Propyfphenethyl alcohol n-Propyl ~O-phenylacrylate See Propyl cinnamate ° ~!-opyl(iso) butanoate See Ilsopropyl butyrate ropyl butanoate See Propyl butyrate Propyll butyrate 2934 172.5151 266 2 5 M 1' 1105-66-8' NRTH CTC' GRDN Source: f- rrPropyl-E-butyrolactone See f-Heptalactone Propyl(iso) caproate See Isopropyl hexanoate Propyl caproate See Propyl hexanoate Propyl{iso}, capronate See Isopropyl hexanoate Propyl carbinol See Butyl alcohol Propyl(iso) carbinoll See Isobutyl alcohol Propyl chemosept See Propyl' p-hydroxybenzoate Propyll cinnamate 293'8' 172.515 324 5 C 11 7778-83'-8' Source: NRTH NIMO' NCC' Propyli 2,4-decadienoate 3648' 2 M 1 2'-Propy! -3;61-d'i methyl pyraz iine 2 -Propyl-3',543,6)-di methylpyrazine Propyl' disullfid'e ~. 3228' 172:515 540 2 B4 629-19-6 Source: VVTRff NCC Propyldithiopropane See Propyl disulfide 2-Propylene acrolein, See trans, trans-2;4-Hexadienall ' Propylene g,lycol 2940 182.1666 4212 2 B1'A 57-55-6 x ' OD Propylene glycol-acetone ketal See 2,2,4-Trimethyl-t,3'-oxacyctopentane ~ ~ PropyJene glycol alginate 2941 172:858' 9005-37-2 x N Source: KLCO ~. . V~ 154 Flavor & Fragrance Materials - 1'98'1I - Allured Publishing l
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Dangerous Properties Of Industr~al Materials Sixth Edition N. IRVING SAX Assisted by: Benjamin FeinerlJ©sephi ,J. Fitzgerald/Thomas J. IHaley/Elizabeth K. W'eisbwrger VIAN' NOSTiRAN~D' REINHOLD COMPANY Mew York
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. k Toxicity Ratings Anexplanation of'.the toxi;city ratings is givenn in the fiol'lowing paragraphs: U= Unknown, This designation is given to substances which fall' into one of the fbllowing categories: (a)~ No toxicity information could be found', in the literature and none was known to the authors. (b) Limited information, based on animal ex- periments was available but in the opinion of the authors this information could not be ap- plied to human exposures. In some cases this i,nformation is mentioned'so that the reader may know that some experimental work has been done.. (c)i Published toxicity data were felt by the authors to be of questionable vaGdit}. 0 = No Toxicity. This designation is given to, materials which fall into one of the folfowingg categories: (a) Materials which cause no harm under any, conditions of use.. (b)' Materials which produce toxic effects on humans only under the most! unusual conditions or by overw•helming dosage. I = Sfight'Toxicity: (a) Acute ll.ocal! Mrterials which on single exposures lasting, seconds, minutes or hours cause only slight efTects on the skin or mucouss membtanes, regardless of the extent of the exposure. (b)' Acute Systemic. Materials which can be absorbed~ into the body by inhalation, ingestion or through the skin and which produce only slighti effects foll'owing single exposures lasting seconds„minutes„or hours, or following iinges- tion of a single dose, regardless of' the quantity absorbed' or the extent of exposure.. (c) Chronic Local. Materials which on con- tinuous or repeated exposures extending over periods ofl ditys,'tnonths, or, years cause only slighuharm to the skin or mucous membranes. The extent oflexposure may be great or small'. (d)i Chronic:Systemic: Materials which cani be absorbed into the body by i'nhalation, inges- tion or through the skin and'which. produce only slight effects following continuous or repeated exposures extendingover, days, months or years. The extentiof the exposure may be great or small. In general, those substances classified as hav- ing: "slight toxicity" produce changes in the human bodv which are readily reversible and which will disappear following, termination of exposure, either: with or without medical treat- ment.. 2' = Nloderate Toxicitv: (a) Acute Locali Materials: which on single i exposure lasting seconds; minutes or hours ; cause moderate effects on the skin~ or mucous i membranes. These effects may be the resul't' of ; iintense exposure fon a matter of' seconds or moderate exposure for a matter of hours. (b) Acute Systemic. Materials which can be I absorbed into the body by inhalation, ingestion I or through the skin and which produce moderate ' effects following single exposures lasting sec- ± ond's„ minutes or hours, or following ingestion: , of a single dose., j, (i:) Chronic Locall. Iv1'aterialswhich on con, tinuous or repeated exposures extending o!ver, periods of days, months or years cause moderate harm to the skin or mucous membranes. (d)' ChronicSyetemic. Mlaterialswhichi can be absorbed into the body by iinhalation, inges- tioni or through the: skin and which produce moderate effects following continuous or re- peated' exposures extending over periiods of days. monthsor years. Those substances cllassified as having '"moder- ate toxicity'"mayproduce irreversible aswali as reversible changes in the human body. These changes are, not of such severity as to threaten life or produce serious permanent physical impainment'.3~ = SevereTox;icity: (a), Acute: Local. Materials which on singfe exposures lasting seconds or minutes cause in- jury to skin,or mucous membranes of sufticient severity to threaten life, or wcause permanent physical'.impairment or disfigurement. (lh)i Acute Systemic. Materials which can be absorbedlinto the body by inhalation, ingestion or through the skiniand which can cause iinjiury of sufticient severity to threaten, life following a single exposure lasting seconds„ minutes or hours, or following ingestion of a single dose. (c)' Chronic Locali Materials which on con- tinuous or repeated exposures extending over periods of days; months or years can cause in- jury to skin or mucous membranes of suflicient' severity, to threaten life or to cause permanenu impairment, disfigurement or irreversible change_ (d) Chronic Systemic. Materials which ean be absorbed into the body by inhalationi ingcs- tion or through the skin, and which can cause death, or serious physical impairment, following continuous or repeated exposures to: smalll amountsextend'ing overperiods of days„ months or years. ~ ~ ~ CG ~ ~. ~ 1
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70 KEY lfG ABBREVIATIONS MSK-musculo-skeletal effects M7PllS-mutation dose 1Vi7fH-rnouth effects mul-multiple routes mumem-mucous membrane mus-mouse MUT-mutagen NEO-neoplastic effects ng.-nanogram, (one billionth of a, gram;1U-4 gram) nmol-nantlmole' nsc-Neurospora crassa. nse-non-standard exposure NTP=Nationali, Toxicology Program, OBS-obsolete ocu-ocular open-open irritation test orl-oral OSHA-Occupational Safety and Health Adlnini'stration, otr-oncogenic transformation ovr-ovary par-parenteral pg-picogram (one trillionth of a.gramIUD112 gram) plln-pigeon Pk-peak concentration pmol'lpicomole PPdS-penipheral, nervous system ieffects ppb-parts per billion (v/v) pph•parts per hundred (v/v) (percent) ppm=parts per million (v1v) ppt -parts per trillion (v/v), preg;pregnant PSY-psychotropic effects PUL-pultnonary system, effects 9a1-qpail RBC-red blood cell effects rbt-rabbiti rer-reetal REGS-standards and regulations rns-rinsed with water S, sec.-second(s) sat,-Salmonellatyphimurium see-sister chromatid exchange. SCP-Standards Completion Program scu-subcutaneous SEV-severe irritation effects skn-administration onto skin SKN-skin effects (systemic)) sl-slightly' sln•sex chromosome loss and nondisjunction sl't -specrfic locus test smc-Saccharomyces cerevtsiaee sol-soluble spm-sperm morphology spont-spontaneous sql-squirrel stm-Serratia marcescenss ssp-Schizosaccharomyces pombe SYS-systemic effects TC-toxic concentration~ TCLo-lbwest published! toxic : concentration TD-toxic dose TDLo-lowest published toxic dose TER-teratogenic effects TFX-toxic effects THR-Toxic hazard review' TLV-Threshold Limin Value tod-toad tox-toxic, toxicity nrk-turkeyy trn-heritable translbcation test TVY!A-time,weighted average TXDS-toxic dose µg, ug-microgram (one millionth of a gram;10+6' gram) umolrmicramole U,, unk-unreported, unknown. UNS-toxic effpets unspecified in source W-week, W BC-white blood cell effects wmnrwoman Y'-year %-percent'.
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1,2-PfROPAN'EDIIOL 2293: EI?:'i ; .. ; ..,.. Currently Tested by NTP'for Carcinogenesis by Standard Bioassay Protocol as of December 1980. TyR: MUT'data: An' exper CARC. MOD orL Disaster Hazard: When heated' to decomp; it emits acrid smoke: 1.2-PRO'PANEDIAIWIIINE Cp1;S'RN: 78900 NIOSH #: TX 6650000, tnf CaH1oN2; mw: 74.15 Flash p: 92°F (OC)„ d: 0:9, vap. d: 2.6, bp: 118.9°. SYNS:' 11?'; DIAMINOPROPANEPROPYLENE DIAM'INE (DOT). TOXICITY DATA: 2 CODEN': yl:n-rbt,1, mg/24H AMIHBC 10,61,54 skn-nbt 435'mg opem SEV' UCDS" 3/12/69 ,ye-rbt 87 mg SEV UCDS** 3/12/699 orGrat LdD50:2230 mg/kg UCDS"' 3/12/69 scu-rat LDLa :2250 mg/kg , ZEPTAT 17,59',1 L5 skn-rbt'LD50I500' mg/kg AMIHBC 10,6'P,54 Aquatic'I'oxiciCy Rating: TLm96: 100-ll0 ppm WQCHIVI'" 4,7,74.DOT: Flammabl'e Liquid, Label: Flammable Liqtud'FER'EAC'41457018;76: ReportedinEPATSCAInventory, 1980. THR: A skn, eye irr. I120D~ skn, orl.. Fire Hazard: Dangerous, via heat, flames, oxidizers. To Fight: Fire., Alcohol foam.. Disaster Hazardi When tiea'tedl to, decomp it: emits tox fumes of NO=. 1,3-PROPANEDIAIVIINE CAS RN'. 109762 NIOSH' #: TX 6825000 mf:' CsHtoNz; mw: 74a15 Water white liiquid', amine odor, completely sol in, water,, methanol and ether. di 0.8881 @ 20Q/20°, bp: 1139:7°; fp: -12°, flash p:~ 1'2Q°F (TOC)i SYNS: 1;3•DIAMINOPROPANE TRIMErHYLENEDIAMINE 1;3-PROPIiLENEDI A M'IN E TOXICITY DATA: 3-2 CODEN: skn-rbt i 50 mg open SEV UCDS** 1/28/63 eye-rbt 1 mg 5EV' UCDS** 1J28/63 orl-rat LD50=350 mg/kg A[HIAAP'23;95,62' orl-rat LD50=500 mg/kg 37ASAA 7,580,79~ skn-rbti LD50:200 mglkg, AIH'u4AP' 23;95;62' TO}CICITY' DATA: 3 CODEN: ipr-mus LD50:250 mg/kg 1+ITIS'•'AD691490 unk-mus LDL''A:200 mg/kg, ATMPA2 32,177,38 Reported in EPA TSCA Inventory, 1980. THR': HIGH' ipr, unk. Disaster Hazard,When heated to decomp it emits veryy tox fumes of HBr, SOr and NOs. 0 1,2'-PROPA'NED'~IOL. CAS~~ RN:~~ 5755& NIOSH~ #:~ TY 2000000~ mf:' C,HJ(J'7; mw: 76.11. Colbrless liquid, practically odorle.cs„ hygroscopic. bp:~ 188!2°,~ flash p: 21'0°F~ (OC), lell = 2.6%t uel =: 1'2'.6~'/0,~ d'c 1.0362 @ 25°/25°, autoign. temp.: 700°F, vap. presse, 0.08& mm @ 20°, vap, d: 2:62; fp: -59°:. SYNS: 1,2-DiHYDRORYPROPANE PROPYLENE GLYCOL METHYLETHSILENE.GLYCOL ALPHArPROPYLENEGLYCOL MONOPROPYLENE GLYiCOL. 1,2-PROPYLEN,E.GLYCOL PROPANE-1~2-D10L TRIM'ETHYL GLYCOL TOXICITY DATA: 3~2-1 CODEN: ipr-mus. TDLo=1',00 mg/kg (1111D preg), KAI'ZAIV' 37,239,62 ipr-mus TDLo: 1'Q0 mg/kg (115D: preg), KAIZA[V' 37,239,62 skn-mus TDLo- 17600 ~mg/kg/2Y- TXAPA9 30;7;74 I: ETA. skn-hmn 500'mg/7D MLD: JIDEAE 5'5',190,70 skn-hmn 104 mg/3D-I, M'iOD 85DKA8'-,127,77 skn-man,109~,d/2D JIDEAE 19,423,52 eye-rbt' 104 mg, JIPETAB 82,377,4'4' eye-rbt 500 mg/24H MOD 28ZPAK -,37,72 orl-chd TDLo:79 gm/kgl56W-1:Ch1S' JOPDAB 93',515',78 orl-rat LD50i:20 gm/kg TXAPA9'45;362;78 ipr-rat LD50:13'gm/kg J[HTAR 31,256,49 scu-rau LD50~28 gm/kg JIHTAR 31,256,49 ivn-rat LD50:6'800 mglkg, NTIS'•'PB280-477 ims.rat LD50:20'gm/kg JIHTABi 31,256.49 orl-mus', LD50:24 gm/kg JIHTAR 21,173',39 ipr-mus LD50:1I1400 mg/kg TJ(l+lPA9'1,576,59 scu-mus LD50':18500 mg/kg JPETAB 650;39 ivn-mus LD50:8000 mgfkg' JPETAB 65A9;39' orl-dbg,LD50:22 gm/kg, JIHTABI 21,173,39 ivn-dog LD50:26 gmJkg' IQTIS'• PB28Q-477 orl-rbt LDLo:20 gm/kg NTIS" PB280-477 skn-rbt LD50:20800 mg/kg NPIRI' Ii,101,74 ivn-rbt'LDLo:4200 mg/kg JPETAB 44,1'09J32 ims.rbt II,DLo:6300 mg/kg JPETAB 44,1'09;32 orl-gpg,LD50:i9' gm/1'eg, J[HTABI 21,173,39 scu,gpg LDLo-1155'00 mg/kg NTIS•• PB280-477 ivn-ckn LDLo:27 gm/kg JPETAB 60,312,37 Reported in EPA TSCA Iinventory, 1980. " A skn eye THR: IvIOD, orL HIGH orl l and d'erl!nal l tox I?oxicity, Ratin& TL.m96.:over, 11Q00~ ppm Aquatic , . 74! Toxicology ReviewAI~Ir*IEAZ - WQCHM' 4 irr „ , ' . in EPA TSCA Inventory,, 11980., 38,409,65. Reported Fire Hazard.• MOD, when exposed to heat or flame. EPA TSCA 8(a) P'relimina'ry Assessment Information~ Cb Disaster Hazard: When heated to decomp it emits tox Proposed Rule. EPA TSCA 8E No: 01!Z80041'-Fol; fumes of NOr. 1979. lowup Sent as of'April ~ PR'OP'ANE' DIISOTHIOUREA , THR:' A sknl eye irr. A hmin CNS. LOW orl, ipr, scu, C8 DIHYDROBROMIDE ims, skn, Used as' an emulsi'fiy' ing, agent and a general~ ~ purpose food additive. It is a substance which migrates C7a CAS' RN: 5442320 NIOSH #: UO 1320000 to food from packaging materials. LNJ mf: CsH„2M$z-2Bt•H;, mw: 354.17 Fire Hazard: Low, when exposed to heat or flame; can SYl`l:'. 2,2' -TRIMETHYLENE-BIB-(2-THIOPSEUDOUREA)t DIHYDRO*BROMIDE. react with oxidizing, materials. SpontaHeous Heating; No.
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229'41 1,3-PIROIPANEDIOL Explosion Hazard: lwiod, when exposed to ilame:. To Fight Fire: Alcohol foam. 1,3-PROPANEDIOL ~ CAS RN: 50'463'2' NIOSH #: TY 2010000' mfc C3H&%; mw: 76.1' 11 Cblorless, odorless liquid, sol in water, alcohol' and' ether. d: 1.0536 @ 25°, bp: 210°-2111°, vap. d: 2'.6s autoign: temp.: 752!°F:. SYNS: 2-DEOXYGLYCEROL. 1;3-PROPIILENE GLYCOL 1,3-DIHYDROXYPROPANE' TRIMETHYOENE GLYCOL BETA-PROPYLENE,GLYCOL TOXICITY DATA: 1 CODENc orl-mus,LD50;4'773' mg/kg, TXAPA9 49,385,79 Reported in EPA TSCA Inventory, 1'980'. THR: LOW orll See also glycols. Disaster Hazard: When heated to decomp it emits acrid smoke and fumes. PROPANE'I'HIIOL CAS' RN: 107039 NIOSH $k: TZ 7300000, mE C3hIeS; mw: 76,17 Flash, p: -4'°F.. SYNS: 3'•MERCAkPrOPROPANOL. PROPANE-I-THIDL, PROPYII.MERCAPTAN'. N-PROPYL MERCAPTU\N' TOXICITY DA'I'A:' 2' CODEN: eye-rbt, 83 mg SE1W' AIHAAP 19;1171',58 orl-rat' LD50=i790' mg/kg AIHAAP' 19; I711,58 ihl-rat, I1C50:7300 ppm/4Hi AIHAAP 19;11711,58 ipr-rat' LD5C1:516 mg/kg AIHAAP 19;1171,58 ihl-mus LC50:4'010 ppm/4H AIHAAP 19;1171,5'8 DOT: Flammable Liquid, Labell: Flammable Liquid FEREAC 41,57018,7& Occupational Exposure to n-Alkane Mono Thiols recmi std: Air: CL 0.5 ppm/ 15M NTIS**. Reported in, EPA TSCA Inventory,. 1980. THR: MOD orl, i'hI, ipr. An eye irr. Violent reactioni with Ca(C)CI)x. Very dangerous' fltre hazardl. Disaster Hazard':: When heatedl to, dncomp it emits tox fumes of S%. PR'O!PANE-2=THIOLL mf: C3HBS; mw: 76:16. Flash p: -31,°F.. THR':No tox data. A very dangerous fire hazard. Disaster Hazard:.' When heated to decomp it emits tox fumes of SO... PRO!PANIDIDE'. CAS' RN: 14'211143 NIOSH #: AGI96250000 mf: C18EI27NO5i mw: 337.46 SYNS: BAYER. NtM PROPANTAN TOXICITY DATA: 2 CODEN: ivn-hmn iTDLo :5 mg/kg :BPR BJANAD 45,1097,73 orhrat LD50:700 mg/kg, TXAPA9 18;118,5,71 THR: A hmn' BPR. R4OD, orl. Disaster' Hazard: When heated to decomp it emits tox fumes' of NOr. 3-PROPANOLAMINE' CAS RN: 156876 NIOSHI #: UA 5600000. mE C9H9NO; mw: 75.13' Colorless liquid, fishy odor. bp: 168° @ 500' mm, flash, p: >1'75°F (TOC)6fp: 112.4°, d: 0:9786' @' 309, vap. press: 2.1 mm! @ 60°; vap: d: 2.59. Very' sol in water; sol in ale; insol in ether. SYNS: BETA-ALLANINOL 3-AMINOPROPYL.ALCOHOL GAMMA-AMINOPROPANOL 3-HYDROXYPROPYI.AMINE 3•A1N'1NOPROPANOL. PROPANOLAMINE. 3-AM1N0-1-PROPANOL I,3-PROPANOLAM1NE TOXICITY' DATA: 3-2 CODEN: skn-rbt 1;0' mg/24H' opee SEV ' AIHAAP 23,95,62 ipr-mus'TDLo:'5700 ug/kg,('11D'prag) 7PJA'DAB'4';14L71 arl;-rat, LDLo-2830'mg/kg AIHAAP 23',95',62 skn-rbt LD50:1250: mg/kg AIHAAP 23,95,62 Reported ini EPA TSCA Inventory, 1980. THR: MOD'via dcrmal and' oral routes. See also amines. A mod strong, base which, from animal exper,, would seem to be a non-specific irr.. Fire Hazard Mod, when exposed to heat or flsme; can react with oxidizing, materials. To Fight Fire:' Foam, CO2, dry chemical. Disaster Hazard: When heated to decomp it emits tox fumes of'NO=. PROPANOLOL GLYCOL CAS RN:' 36112955~ NIOSH #: TZ 08000()O mf:l C,aBi11403; m'w: 2118'.27 SYNS: . ~ 1-(2 ~,3 ~'-D1 HIYDROXYPROPOX,Y) ~. 3-(A LPHA-NAPHTHOXY)-~I ~2'PwW NAPHTH'ALENE PANEDIOL TOXICITY DATA: 3'-2' CO'DENt orl-mus LD50=6900 mg/kg JMCMAR 7,167.64 scu+mus LD50:'828 mg/kg JPETAB'93;470,48 ivn-mus LD50=88 mglkg, JPETAB' 188;136;74 THR.: HIGH ivn; MOD scu~ orl.. Disaster H'azard.' When heated to decomp it emits acrid smoke and' fumes. 3•PR.OPANOLPYRIDINE CAS RN: 2859678 NIOSH' #: UT 7390000 fb ' mf: C8H„1NO; mw; 137.20' TOXICITY DATA: ivn-mus LD50 : 9 g0' mg/kg 3 CODEN: CSLN?I' N}0#01584' ' 1%4 r~1 (PA '. N '. Reported in, EPA TSCA Inventory, 1980. C) THR: HIGH ivn. N.
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U THE MERCK INDEX AN' ENO1'OILOPEDfA OF G1HEI191I.CAli.S, DRUG.S';~ AND, BIOLOGICALS TENTH EDITION: I Martha Windholz, Editor Susan Budavari. Go-Editor Rosernary F. Blumettii. Associate Editor Elizabeth, S. Otterliein;Assistant Editor ~-f q8 .;2-. Prnblished' by . NIERC'K& CO., INC. RAHIIM,A,Y. N.J.. U.S.A. G~h ~ 1983 t;0 I4 ~ C5 .W
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0 n+Propylbenzene 15.35%,: N'. 23:70%: .aldehyde + ammo- n, Schwoegler, US:, ,w pressure catalyticc md, Cassis; J: Am:, ic hyd'rogenatian,of' par. 3,117,162 (1964 ua odor. df; , 0:719i. .?t; closed: cup IO'F ether. Keep tightly. H. F. Smyth et'aL, ;c crystals. mp 157- ts cliloroform. Keep n sensitizer. :•opane. CvHt=; mal. Z:H=CHzCH'y.. Rrepol zyli.nagnesium chlo- Syn. co1L vol. I, 471', t 1i59:Y; bil 135.7'; 36.8'; bpN 43:4!; bps iy sol lin, water (0:06' n rats: 6040'mg/kg., cicoL 2, 327 (1964). solvent for cellulose .pane. C3H7Br; moll t% CH;~CHI CH=Br., '; bp 71'; n# 1.4341. :ohol, etc: ~~ G Op84'S 24.58%. bp 143'!; n 1.4005: ether. ' sa orally et aL. Foad I Cosmet. +pane. C3'H;CI; moll %. CH,CH2CH}Cl+ : presence of'ZnCI=: T to -123`; bp 46- water, miscible with trbonachloridic acid C^CIU~,• mol wt 0 '26:116. C3H1O- 16". Gradually dec chloroform, ether. to,eyes and mucous 1 etylarnina)-2,4; 6-tri~ diacetylamino)-2.4',- Pulmidbl. C,'4Hp- 2.20% 1 59,40%. : N propyll 3-acetamido- . Brit. pat. 898,780 lue rc -n), thylen,., methyleth- 14,37%. H=C-CHI- he refining,of gaso- line. CBtalytic or thermal cracking of hydrocarbons allvays' yields propylene. If'necessary, it can be obtained by catalyt- ic dehydrogenation,of'propane. Reviews: R. F. GoldEstein The Petroleum Chemicals Industry (New York-London. 1949) p 114 sqq.; Sherwood, Ind. Ch'emist'1960,, 542-546; Chim. et Ind.1961, 576-587; Haney. "Ethylene. Propylene and 1-Butene" in Vinyl and Diene Monomers., E: C. Leonardl Ed. (Interscience, New, York,, 1971) pp 577-689; M. R., Schoenberg, et aL: in Kirk-Othmer Encyclopedl Chemical Technology vol. 19: (yWiley-Ihterseience: New York, 3rd edl. 1982) pp 228-246_ Flammable gas. Burns with yellow sooty flame. d 1.49 (air = 1.0). mp (triple pt)' -1'85: bptw -48': Critical I temp 91,.8:'. Criticalipressure 45.6 atm. Heat aflfusion 717:6' cal/mol. Liquefies at 7-8 atm. dm (liq) 0.5139! Flammable limitsin air: 2l440.3% (6y'volhme): Latent heat of vapor- ization at bp: 104.62 eal/g, Dipole moment 0.35: np4o 1.3567. Surface tension at 90': 16.70 dynes/cm. Shipped as a liqpefied gas in lbw pressure steelI cylinders under its own vapor pressure af about:136 pounds per square inch, Con- taminants are propane, ethane. carbon dioxide. USE: 11n polymerized fotTtt as': polypropylene plastic. Raw material in the manuf oflacetonef isopropylbenzene, isoprop- anol, isopropyl halides, propylene oxide. Caution: Simple asphyxiant: High concns cause unconsciousness. 77511 Propylene Chlbrohydrin. 2-Chl'aro-i,propanol;. 2-chloropropyllaleoholl C3IiftCIO; mol wt, 94.54. C 38.1i1%a H.7:46%, Cl137:50%, O' 16.92% CH CHCICHZOH: Colorless liquid; pleasant odor: dA 1.103; bp 133-134'; ep,' 1.4362. Sol in water, alcohol, etc. LD., orally in rats: 0:22 ml/kg; by skin penetration in rabbits: 0:48' ml/kg, Smyth et'aL.,A'm: Ind.Hyg: Assx J.' 30, 470'(1969). USE: In prepn of' propylene oxide (q: v.).. 7752. .ur-Ptopylene Chlorohydrin. I-Chloro-2-'propan- al; 1-chloroisopropyl alcohol. CsHyC1O; mol wt:94.54. C R 11%. H'i 7:46%a Cl, 37.50% O~ 16.92%.. C1CH=CH(OH)- CH'y. Colorless liqpid. d2o 1.11'S; bp 126-1',2T; nj 1 .4392. Sol in, water, alcohol., etc. 7753. Ptopylenediamiite, 1,2-Propanediamine. C3FdtoN=; mollwt 74.13. C'48.61%a, Hl 13:60%a N 37:8l CH'yCHI- (NHr)CH=NH=. Prepd from propylene dibromide and,aleo- hohc ammonia~at 100": Eztremely hygroscapi¢, strongly alkaline liql Rapidly ab- sorbs maisture to form a hemihydrate. dts 0.878 in anhydr form. bp I119+120'., Very sol inwater, Keepp tightlyclosed: USE: Imconjunction with cupric sulfate it is a very, sensi- tive reagent for mercury. 7754. Propylene Dibromide. 1,2-Dibromopropane. C3- H4Brr; mol wt 201.91. C I7:84%: H 3:00%, Hri 79.16%. CH3CHBrCHI2Br. Prepd from propyl bromide and Br inrthe presence ofl AlCla or AIBr3. Colorless' liquid. rl bp 140-142`; n001.5203; d=' 1.933. Slightly soi in water; miscible with organic solvents. 7755. Propylene Dichloride: 11.2-Diohlbropropane: C3- HJCI=; mol wt 112.99. C 31.89%: H:5:35%a Cl 62.76%. CH3CHCICH=C1. Prepd from prapyl 1 chloride and Sb=Cl~. Flammable; mobile liq. Odor'of chloroformi d2zs ' 1'.159; bp 95-96. Solidifies below -71X. np 1.4388. Flash poinr (ASTM open cup) 21f' (7('F): Despite the low flash pc in does not catch fire:readilyin industrialiapplications. Firept38': Slightly sol' iwwater; miscible with organic solvents. LD, orally in ratso 1'.1:9'ml/kg, H: F. Smyth etaL. A'm. Fnd.' llyg; Asroc. J. 30, 470:(1969). USE: Oil.and!fatsolventt in.drycleaningfluids; in degreas*ing,, In.insecticidal,fumigant mixtures. Caution: May be ir- ritating~ toeyes, mucous membranes, and inhigheoncns, narcotic.. Has caused liver, kidney necrosis in exptl animals. 7756. Propylene Glycol. L,2-Prapanediol::methyl glycol; 1.2-dihydroxypropane: CyHlsiO=; mol wt 76'.09. C 4'7.35%l Hi 10.60%, 0 4'2.05% CHaCHOHCHzOHi. Prepn, from gl$cerol: Raschig. Ptahl.,Ber61„185'(1928). Ptepnaf'le- varotatorypropylene,glycol from hydroxyacetone by,yeasty reduction: Levene: Walti, Org- Syn. eoll. vol.. 11, 545 (1943)'. Synthesis'of S'-('+)-fotm: C. M'elchiorre: Chem. lnd. (L.on. don) 1976,.2181. Manuf from propylene.oxidebyhydration:e onsult tfte cross index before using this section. Propylitldone Faith, K:eyes & Clark's Industrial Chemicals, F. A. Lowen- heim, M. K.,Moran Eds. (yWiley-Interscience,,New York, 4th ed., 1975) pp 688-691. Taken internally, propylene gly- col' is harmless, probably because its oxidation yields pyruvic and acetic aeids, cf. Whitmore. Organic Chemistry (New York, 1951). Review on toxicity, metabolism and biochem- istry: Ruddick, Toxicol.' AppL' Ph'armacnL 21„ 102I (1972): dl-Fotm, hygroscopic,.viscous.liquid. Slightlyaerid taste.. d~' 1.036; freezes at'~ -59'; bp.~ 188.2'; bp~ 1,68:1'; bpmo 149.7'; bptoo, 132A'c bp,0 1 i19:9';' bpb 1I11.2`.' bpm 96.4'; bpto 83.2'; bpj 70:8'; bpiA 45:5'. Flash ; pc open cup: 21109F (99'C): Miscible with water, acetone, chloroform. Sol in ether:. Will dissolve many essential oils, but is immiscible with 1 fixed oils. It is a ~ goodl solvent for rosin. Under ordi- nary conditions propylene glycol is stable, but:arliigh temps it tend's':to oxidize giving rise to products:such as'propional- dehyda lactic acid, pyruvic acid and acetic acid. LDys orally in rats: 25 ml/kg, W. Bartsch eraL, A'rzneimittel=Fotsck 26j 1581 (1976). /-FOrrn, bpi= 88-90', bpt 187-189'. [a]~o -15:0': d=Form, bp 94L96". [a] + 15:84% (neat): d2s 1''.04. USE: As nontoxic antifreezrin breweries and dairy estab- lishments: Solinent:fior pharmaceuticals. Substitute for, eth- ylene glycol and glycerol.. In the manuf.of synthetic resins. As inhibitor of' fermentation and!mold growth. As mist: to disinfect air. As emulsifier in foods: THERwP'ehT: Pharmaceutie aid I(humectant; s'olvent):. THERMP'CMTYvET): Glucogenic (orally) in ruminants. As a solvent for drugs. 7757. Ptopylene OO 7tide. M'ethyloxitaane; propene, oxide: CjHsO;~mol wt 58.08. C 62.04%, H 10.41%. 0 27:55%. Re• sults from the action of' KOH (aq):on propylene chlorohy- drin. Reviews: Holden in GlycoLs: G. O: Curme, F. John- ston, Eds.. A.C.S. M'anograph Series no. 114 (Reinhold, New York. 1952) pp 250-261; Faith Keyes 6t: Clark's !n, dustrial Chemicals. F., A. Lowenheim, M'. K. Moran, Eds. (Wiley-Interscience. New York, 4th ed., 1',975'): pp 692'-697; R. 0. Kirk, T.,]: Dempsey in Kirk-Othmer Encyclopedia of Chemical Technology vol. 19 (Wiley-Interscience, New York, 3rd ed., 1982) ~ pp 24'6-274.. z 0 _ C. 3 Colorless ethereal liquid. Extremely flammable. df 0.859: fp -1'12:1:3'; bp 34.23". Flash pti closed cup: -31'F' (-35'C). Soly in water (201: 40.5% by wn; soly of'water in propylene oxidt: 12.8% by wt; miscible with alcohol, ether. LDyo orally in rats: 1.14:g/kg. H. F. Smythi et al..,J: Ind; Hyg. Toxicol' 23', 259 (1941). USE: Chemical intermediate in:prepn of'polyethers to form polyurethanes; in prepn of ~ propylene and dipropylene g1y- cols;; in prepn of, lubrieants surfactants, oildemulsifiers:. Also as:solbent; fumigant;,soil sterilant. 7758. Propyl Ether. 1,1'-Oxybispropane;,dipropyl ether. C.Ht40: mol l wt 102.17: C 70:53%: H 13.8174 O: 15'.66 0'. C3HtOCs+iT. Obtained by heating propyl lalcohol with benz- enesulfonic acid. Mobile liquid. Extremely flammable. d"' 0:7360~ mp -122'; bp 89-91'; no' 1.3807. Flash pt, open cup: - 5'F (-20°C). Slightly sol in water: Sol in alcohol, ether. Highly volatile. Tendfi too forwexplosiveperoxides.e csp when an- hydr. Do not:allowtoevaporate.to neard'ryness:. 7759. Propyl Formate: Formic acid pmprl ester. C4; HsOj; mol wt 88.10. C 54:53'7. H 9.15'0., 0:36L32'7,. HiCOOC,HT. Colorless hqpid; pleasant odor. dto 0.901; mp -93': bp 81-82': Flash pt, closedlcup: 2TF (-3'C). nD 1'.3771. Soli in 45 parts watert misc with aloohoU ether. LDw orally in~ rats: 3980,mg/.kg,,Pl.M. Jenner et.aL,Food:Cosmef.' Toxicol. 2, 327 (1964). 7760. Propyl G®IlateL 3L4:S-Trihkd'rox!vbenzoic acidpro- pyl eVer:n-propyl gallate; gallic.acidlpropyl.ester; PGcPro- gallin P: Tenox PG: C,OHt=O3: mol wt 212:20: C 56.60';.•: H 5'.70"f, 0 37.70%I. Spectrophotometnc determn C. S. Sas- tryerr aL.. Talanta29+.917. (1982). Effectsonsurvival.of' SOccharomyce: Food Prot 4i6:. Augustin. S. h Crystals, mF in alcohol' _ ' cottonseed' oili g/1100:g. Dar Synergic with g/kg, Patty's.. D. Claytoni F York, 3rd' ed.. USE:. AOtiarwaxes, transfoi 7761. , Prap: aminr, 1-cyclo oxyephedrine; 159:28: C 77.: hydrogenation catalyst and gi J' AM. Cltem. . 746(194gtoS df-Form, oil 92'-93f: volatili.. slightly sol in its aq, solns ar chloroform. etl dl-Form hy 1'28': Sol,in w d'-Form. oil) d=Form hyc + 1'4:73': Sol ; l-Form. oily t-Form ethyl yl=2-imerhylat: barbital comp Mtrliasin. 1=Formi hyd1 -14.74'': Sol i i THERAP CAT: 7762. Prop. HkClt; mol wt CH,CH}CHCI: , aldehyde. Liquid. dN I many organic s et al.: Arch. In. 7763. Prop,• 170.01. C 211. Prepd by heati phorus. Colorless or -98'; bp 102-; cible with aleoi 7764: Prop~ acetic acid pm; propyl ester; f piodone;'DionK H 2.4'8%: 1', S6 combe, Brit. 1 Tomich et aL. Consult the cross index, before using this 8'7'491264'
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Clinical Toxicology of Commercial Products ACUTE, POISOlNIN~.G R O'B' E R'T E. G OS S E L1N', Ilil!1- D.,, Ph.D. Irene Heinz Given Professor of Pharmacology. Dartmouth Medical School. Hanover. New Hampshire HAROLD C. HODGE, Ph.D., D.Sc., Professor and ChairmanFmeritus of Pharmacology and,Toxicolo~%% School,af Medi- cineand Dentistry, The U'niversity of Rochester„Rochester, New York: Professor in Residence of PharmacoloRy and nr+nlBiology„ University of Califbrnia; San Fran- cisco; of Environmental ToxicoloRr: and of PharmacoloR)'and'Medical Thenapeutics, Unit+errnitp of California. Irvine. California: ROGER P., SMiI!TH,Ph.D. Professor of ToxicoloRy„ Dartmouth 1Vfedicai, School, Hanover, Neu, Hampshire. MARION N. GLEASON, M.Sc., (h.c.)' Honor+arv Associate Fellow, American Academy of Phdiatrics:, Formerly Research Associate in PharmacoloRy. SchoolofMedicine and'DentistrY, The Unioersity of Rochester. Rochester, New York: Fourth Edition WILLIAMS & WILKINS Baltimare/Londan I ,...
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~ 5F:C'1'IO N l.. E`IltS'1 All) A,til) fiMEHGE\('Y THEATMF:N'i 4 TA13LE 1-l. Tbxicit% Batin{t+,r 1'rnhrdrle (h:d L.E7IHAI. IJdne t H umaM (i la>. 1 h,..c Fur 7U kC. tx•rn„n f 1:,b.1 b ji. 6 Supert'oxic 5 Extremelc toxic 4 Verctoxic 3 Moderatolu toxic 2' Slightly toxic 1 1'r'acticallv nontoxic less than 5 mg./kl;. 5-5N mg./kt:. 5(1,5O1, mg:/klt;. Q 5 :;, RmAg:. 5-IS gm./kg. above 15 gm./1:{ _ ?l,tastr (less than 7 drops) Between 7 drops and I teavpeOnlut Ret ween I tsp. and'1', ounce Between 1 oz. and I pinl (ur I Ibi) IBi+tween lipt. and 1' quart More than,l quart (22IIh.)' Y II I - estimates may be useful! in prognosis (Jones and Work, A'merican'Journal'of Diseases of Children. 102: 427, 1961). If the toxicity rating implies a poor or equivocal prognosis (with respect tomortali't'y or mnrbidilt_v)l even the a~sanpto- matic person should be'examined' as soon as possible. This is important even if the alleged exposure occurred' many hourss before. Some toxic agents produce severe sequelae after long periods of latency. A situation like this represents a challlleng- ing opportunity to the therapist. 2'. Has the' patienit voznit.ed'?' If not„ and if the poison iss thoughtl to have been ingested, suggest one of the following emetic stimuli. None ofthese procedures shou6d''tie attempted if the patient is unconscious or semiiconscious,, or if the ingested poison, is thought to have been a strong alkali, a mineral acid, or kerosene. Severe heart disease and pregnancy are sometiines valid cont7aindications, If successful, an y one of the f"4rst three measures (a-c)' shoulld'' indiace vomiting within 2 to 3 min'utes, a. Tickle or gently stroke the back of'the patient's throat Induce vomiting withl a finger. With, a child (vsihomaNbiteY use a bluntt probe like the handle of a teaspoon. Mcchanicallly iinduced'emesisiisseldomextensive enough, tobea:de-q,uateo b,,, Have the patient drink one or more glasses of vwa'rm, water containing a teaspoonful of'' mustard powder. Mix the drv mustardwith water just before drinking. c. Repeat procedure' (a')', above after the'stamach has been distended with fluid (see 3' below). d. If available, ipecac syrup (USP) may be ad''ministered', by mouth. The conventional emetic dose is said'to be 8'ml''., but a singlle dose of 15 to 201ml. has been given without untowardl effects to many young children who had ingested potentially toxic substances. Vomiting under these' circumstances is not immediate, but 56% : of the patients vomit within 15 minutes andl 88% within 30 minutes. (Robertson, American Journal' of Diseases of' 1 x ,
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120 SECTION II: D. INGREDIENTS INDEX. 401 401 Z°riethylene Glycol Toxicity rating: 2(?). This compound has a lower acute toxicity than diethylene glycol but' a higher toxicity than propylene glycoll Symptoms are presumably like those due to ethylene glycol, but there is no evidence of decomposition to ethylene glycol in vivo. See also: Ethylene G1yco1, Reference Congener in, Section III. Ref.: Xare1 et al., 1947; Latvemand Molitor, 1939;, Lawter and Vr'la„ 1940. 402' 402 Polyethylene Gdyeols Toxicity rating: 1' & 2. If a numeral is included in the name; it represents the approximate mean molecular weight. Fractions withimolecular weights of 600 (and below)'are liquid, of'1000 (and above):are solid. The higher the molecular weight the lower the toxicity, perhaps partly because the long,polymers are so incampletely'absorbedfrom the boweL Very large doses are required'to,kill animals and'deathsare renal in origin (not due to primary central nervous depression)l See also: Ethylene Glycol, Reference'Congener in Section III. Ref.: Carpentetand Shaffer, , 1952; Smyth~et al., 1950; 1955. 403 403 Carbowax Toxicity rating:! ll. Solid,and'semisolid polyethylene glycols. A series of waxy substances with mean, molecular weights of 1000 and higher(indicated by the numeral following this trademarked name).,In. animals the toxicity decreases'wit'hi increasing molecular weight. With massive doses some animals diee from kidney injury. No human poisonings are known. See:also: Ethylene Glycol, Reference'Congener in Section'lll. Ref.: Carpenter and Shaffer, 1952; Smyth~et al., 1950; 1955., . 404 404 Propylene Glyeoll 1,2-Propanediol Toxicity, rating: 1. Toxicity is said to be similar to that of glycerine and is therefore practically nontoxic:, No:untoward reactions described in man{,but large oral doses in animals may produce central nervous depression and minimal, kidney changes. See also: Ethylene Glycol, Reference Congener in Section lll: Ref:: Davis and Jenner,,1959; Thamas et all,, 1949: 405 405 Polypropylene Glycois' Toxicity rating: 3. Name is often followed by a numeral which indicates approximate mean molecular weight4 Unaccountably much: more toxic than propylene glycol or even ethylene gl'ycol in, laboratory animals. Polymers with molecular weights of about 1000 iseem, to be more, toxic than longer or shorter homologues. When ingestedlor injectedlin dogs, ventricular extrasystoles result:. 406, 406: 1',3-Butaniedio[ 1,3-Butylene glycol. 'Iloxicity rating: 2(?).. Said to ~ be s'lightly more toxic than propylene glycol, but has been tested as a parenteralidrug solvent: Subcutaneous LD., 16.5 ml./kg. in mice and 20.11 ml./kg. in rats. See also: Ethylene Glycol, Reference:Congener in Section lIl:, Ref.: Spiegel and Noseworthy;,1963: 407 407 Hexylene'Glycol 2-Methy l-2, 4'-pentaned iol I Toxicity rating:~ 2 or 3. Used, in hydraulic brake fluids, printing, inks, textile dye vehicles, and recommended' as a solvent for some pharmaceuticals. Lethal doses in animals producedi muscular: incoordination which progressed to a narcosis lasting for several hours; death,was delayedYor 1 to 4 days. Evidence of slight' liver and kidney damage on chronic feeding; Human subjects have ingested 5' gm: dailyfor 5 days without apparent ill effects or urinary abnormalities. Eliminated' in urine, partly (20'to 25%) in conjugated forms. Said', to constitute a negligible, hazard on intact skin, but when gauze impregnated with a,dressing containing 80 per cent hexylene glycol was usedlon 4f1r3 pediatric patients with extensive burns, 36'exhibited, highly variable periods of'coma (hours to weeksl. Almost: half of this comatosed group eventually expired in renal failure. See also: Ethylene Glycol, Reference:Congener in Section,I'IL Ref.: Jacabsen: 1958; Procter,,1966t Woodward et al.,, 1945. 408' 408' 1,2;6'-H~ex:anetriol Toxicity rating: 1. Hygroscopic viscous fluid, miscible with water and' used as humectant and plasticizer for hydrophilic films. Acute oral LD,,, in male rats 16 ml.lkg.;,intraperitoneally as a 50 per cent, solutionn in water, 10 gm./kg.; and'intravenously as undiluted material, 5.6'mi./kg. Two ml_fkg. applied to shaved rabbit skin 30;times over 6'weeks was without effect. A 30 per centi solution in, 0.75 per cenG, saline was only slightly hemolytic in vitro. Almost 80~per cent of a large dose appeared within, 24 hours in the urine of rats apparently unchanged. There was a significant increase in the urine oxalate, but it accounted for less tham 0:1`.?a of'the intubated dose. It is a moderately good diuretic in rats. Fed: to rats over a 2'year period a 5' per cc year and produ hexanetriol is:inr of compound.. See also: Ethylei Ref.: Smyth et a Non-fatty estert Diethylene glyco Toxicity rating: : ether (= Carbitt produced by ethc more toxic by ski See also: Ethyler Ref.: Karel et al. Toxicity rating:~: slightly more tox:. See also: Ethylerr i.e., Laurate, ole: Toxicity rating: diet'hvlene glycol, See also: Ethyler.. Ethylene glycol n acetate, Dowanol Toxicity rating; corresponding mi Oral toxicity (an probably higher:, .See also: Ethylen Ref.: Anon, 1947 e.g:,, Ethylene gh Toxicity rating: ~ : ethylene glycol. 'I Speciall problems See also: Ethvlen Ref.: Anon.. 1947 Non-fatty ethers Diethylene glycol Toxicity rating; 3 than the eth_vl der toxicitv and toxic .tiee also: Ethvlen Ref.: l:urelt et al.. Ethylene glycol n '1'uxicity rating: 4.. as the ethyllderiv See also: Ethylen Re+f.: Smyth et al e:/;.. Crag 11v rep4 "D,,xicitv rating: :
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FOOD DRUGI COSMET!C. L A W' R E!P, O, R' T' E R' . Scope~ of Reporter. The Reporter is devoted' primarily to the Federal Food, Drug, and' Cos- metic Act and the Fair Packaging' and Labeling Act, as administered by the Food and Drug, Administration, the Poison, Preventilon, Packaging, Act,, as administered by the Consumer Product Safety Commilssion„ and the Compre- hensive Drug Abuse' Prevention and Controll Act, as administered by the Drug Enforcement'~ Administration. These Acts are reported in fulI text,, along with J, the texts of' pertinent regulations, proposals, rulings, decisions, and other II developments described at ff 5. A number of' federal "related! laws," such as j'I the Virus, Serum, and Toxin Act of 1944, are reported in full text, with sum.- I maries of selected court decisions. Similarly, state laws of general application to food, drugs,, aridi cosmetics are reproduce& in full text, and summaries~ of' selected rulings and decisions are also reported. In addition, related state laws pertaining t'o specific products or areas of the food, drug, and cosmetic industries are identified in separate lists of "°Special Laws" with official cita- !. '{" tions, for those who wish to consult the official texts. These "Special Laws" are laws governing, standards,, packaging, and labeling ofspecific prod'ucts: All regulations issued! by the Food and Drug Administration under the , Food, Drug, andl Cosmetic Act, the' Fair Packaging and Labeling Act, and the ` Virus, Serum, and Toxin Act of 1944 are publishedl in full' text, as are regula- tions under the Poison Prevention Packaging Act4 as amended' by the Con- sumer P'roduct Safety Commi'ssion. The f'ul'1 texts of the regulations issued by the Drug Enforcement Administration, implementing the Comprehensive Drug Abuse Prevention and Control Act are reported. Regulations issued d under some of the "related laws" in the Federal, Laws divi:sion are not' re- ported. No state~ regulations are reported. Federal and Stat'e'court decisions are reported. Primarilly, these decisions , wi'll be those cases t'hat imterpret'~ or apply the provisions of' the Federal Food, Drug, andl Cosmetic Act' and the basic food, drug, and'' cosmetic laws ~ of the states: Cases that arise under the various state or federal "related laws" are reported on a selective basis: HOWW' TO'CITE THIEI REPORTER 1, li l Citations to FOOD DBUIG' COSMETIC I.AW' REPORTS are accepted by courts and administrative agencies because they leadl to, authoritative: data, some of' which is available exclusively here. Just combilne the.let'ters "CCH"' wiith the name of the Reporter and the paragraph number. For example, the food additive regulations may be cited "CCH Faon Davc~ CosMEric LAw REPORTS, f 55,300:" A particular section of'the regulations could be referredl to: by the speeiific paragraphi of the Reporter where it is: reprod'uced: CO.wM,M~E~R~C~m, C*LEARIIATG~ ~HO~USIE,J1N'CN, PU~BL/iS~.HEIRS of T'O4-~~1'~.C'A4.., 1..A~WJ R~~.EP~G~t4..T5~ 4025~ W. PETERSON AVE.,, CHICAGO, ILLINOIS 6U646
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944 2-2-81 New Dev!elloprments~~s standard procedures, but data derived using OECID guidelines,fior these t'estss rr,visllbe acceptable. Itis also recognized that special detaireqvirements may dictate use of specialltests. 4.Food'.Safetg! and Quality ,Service. . Although the Food Safety and Quality Service does not'usualdy require private iitdbistry to conduct 1he'type of tests ineluded!in the I12LG and OECDD guid'elinesl it fully supports andlwill encourage their use, by laboratory contractees of the A,gency and by those' submitting data to the Agency for' review: ~Ir ~t' ~k ~F iU 4"II„1!411 Dated: January 15, IBOL. Susan King, Chairman, CansumerProduct Safety Coaunission. Iloaglas ItL Q:ostle, Adtninis'trotor Ent+ironmentr7l Ptowtion Agencj& lece E. Gbyan, Commiasioner. Food'andlJtvg Adminfstfntton. Caro1 Tucker Far®man, Assistant!Secretary; Food'and Consumer Service, Departmentof Agriculture. Eula Blngbamr Assistont'SecretaryforL'obor', Occupationol Sa fet yr and Efiealth Admfnistl+ution 140,838 SUIMIIIIAAR'Y OF CONCLUSIONS ON SAFETY OiF'GRAS A'N'D PRIOR SANCTIONED SUBSTANCES Fed'eration of American Societies for Experimental Biology Report, deted April 30, 1980; ~ released December 1980. ~Reprod'uced ~ belovrr is a summary of the final report to the Food and Drug, Admini'stratiow by the Federation of American Societies for' Experimental: Biology's Select Committee on GRAS Substances concerniilg, the Comanittee"s evaluation of'pre-19'58 food ingredients considered either prior sanctioned or generally recognized assafe:fncluded is a t''abTe (Exhibit 2) of'the substances evaltitated by the Committee with codes to identify the Committee's conclusions as to each substance. The five codes and their inter- pretati'ons are explained in Exhibit 3+ Exhibit 4 is: a llist of requests that the Committee received from the FDA for the'evaluation of'addationa'1lsubstances: Therepcirti'sdiscussedat¶I4U;79i2.See'¶ 58{©15 FINAL REPORT-FDA 223-75-2004, "Evalu+ ation of'. GRAS fvtono- graphs: (Scientific Litera- ture Reviews)" For Periodi M'arch28„ 1972 t'hrough March 30;. t980:, In accordance with the provisions of Contract No. FDA 223-75-2004, dated Mgy 22„ 1975, bhee contractor has' evaluated and'submittedlreportsto FDA on the health aspects of the GRAS and prior- sanctioned'substances covered in 83' monographs'. provided by FDA,, and' on additionat related substances that, were requested by FDA. In a previous' Contract, No. FDA 72-85, the health aspects ofl the substances covered in 35 other monographs were evaluated,and reports submitted to FDA. A totaU of 118 monographs was received and reports were submitted on the evaluation of 415 substances under these two contracts. Of these'* ' substances, 33'5' were evaluated under the present Contract No, FDA 223.75-20041. Safety evaluations were performed bya review committee, identified as the Seleeo Committee on, GRAS Substances (SCOGS)„that was selected and' Food:Drug Drug Cosmetic Law & eports appointed by the contractor. Initial appointments, of the 1'1~membencommittee were made,under the, previous Contract (FDA 72!85): Membership of the Select Committee, and periods served,, are given in Exhibit 1'. [E>ahibit I omitt'ed'.-CCH'.I One member resigned! and a replacement was ap. pointed! during the current contract period. Thirty - seven,meetings of the Sel'ecti Committee were held during the period of the currenncontraeti, May 22, 1975' through: March 30, 1980. The enclosed Summary, Table (Exhibit~ 2) lists substances evaluated„dates that the corresponding monographs: were receivedl dates that reports (numbered as given in column, 1): were sant' to FDA, anct the National Technical Information Service (NTIS), numbers assigned to thereports that are available at this date: All reports senrto FDA after M'ay 22„ 1975; were completed under contract, No. FDA 223-75-21104! As' indicated in the Summary Table (Exhibit 2), announcement of opportunity for public hearing was made in the Federal Register, for the tentative reports on all monographs evaluated under Con- tractNo. FDA 223'-75-20tyi. The Summary Table lists the dates that hearings were held, if requests 14m,,8''3'8''
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41,142 fV'ew Developments were received. Also indicated are the reports for which no requests for hearing were: received„those, for which requests, were,receivedlbut were subse- qpently withdtawn, and those for which only writ- ten statements were submitted in lieu of oral presentation. The conelitsions reached with respect to the safe- ty of the substances evaluated are indicated in the Summary Table (column 3) by the numbers 1-5. The corresponding conclusion statements and the interpretation,of these statements as agreed',upon by the contractor and the technical representative of'the contracting officer, are given in the attached statement entitled "'Conclusion Statements and!In- terpretations of' Statements" (Exhibit, 3). Exhibit 41 lists requests that were received i from FDA to evaluate the safety of' additional substances not identified lin, the monographs,, or to evaluate data that had become available after final reports had been submitted'to FDA:. The latter re- quests were generally answered by letterafter con- sideration by the Select Committee. However, in the case of the request forevaluation of new infor- mation on glutamates,, SCOGS-3'7a, and protein hydrolyzates, SCOGS-37b, the data were so exten- sive that'news supplementallreports were prepared. In, the case of'iron and iron salts, SCOGS-35„the report prepared',under the previous Contract: (No. FDA 72-85'):was revised, a public hearing held, and a revised report:submitted to FDA. As stated I in, the Introduction section of the reports submittedlto FDA;, the scientific literature reviews (monographs)fhrnished by FDA were sup- plemented' by literature searches of over 30 scienc tifie and statistical reference sources and compen+ dia that:are generally available; new, relevant books and' reviews and literature citations, contain- edI in them; current literature citations obtained 944 2;2-at, through retrieval, systems oflthe:National Library of'Medicine; searches for relevant data in the,files of FDA;,and by the combined knowledge and ex- perience of'the Select, Committee and the contrac- tor's staffL Relevant information also was obtain- ed from industrial companies and' trade associa- tions,. The following reports of special supplemen- tal literature reviews were prepared andlsubmitted, to FDPI: Review of the 1972-1976 Literature oni the Health Aspects of CoppenSal'ts as Food Iingre- dients: (PB-275'749) Review of the Recent, Literature on the Health, Aspecm of Cases. as Food Ingredients. (PB-275 70) Review of Recenu Literature on the Health Aspects: of Lecithin as a, Food Ingredient. (11' 75'1) , Review of the Recent Literature ofl the Health Aspects of' R'iboflavin, and Riboflavin 5''-Phosphate: as Food Ingredients: (PB>275 753)i Review of the Recent Literature on the Health Aspects. of Niacin and Niacinamide as Foodl Ingredients. (PB'.275 752)' Review of'the Recent Literature on the Health Aspects: of:'Vitamin B;, as a Food 6ngredient. (PB?275' 755), The report,, "Evaluation of the Health. Aspeetss of GRAS Food Ingredients: Lessons Learned and Questions Unanswered" ; prepared l by the Select Committee, was published in, the October 11977 issue of Federation Proceedings. As requested, two hundred reprints were sent: to:the Contracting Officer's Technical Representative and the GRAS Review Branch. ' 140,838 QQ 1981, Commerae Clearing I$ouae, Inc., ( ( ( 0
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..A Date Opportunlty Date ~ SC0GS SCOGS ManngraFh for Hearint Report Sent ~ O : Report No. Substances Evaluated Conclusion Received Announced' Hearing Datye to FDA NTIS No. 1 A 09 01 tiJ ~ 25 Cellulose (contlnued) Sodium carboxymethyl cellulose 1 6 Ilydroaypropylmelhyl cellulose Elhyl cellulose (In packaging) Cellulose acetate (in packaging) Carbonates 1/03/73 8/29/75 I/R 1/21/7S 8-2S4 S3S Calcium carbonate 1 Potassium bicarbonate 1 Potassium carbonate 1 Sodium bicarbonate 1 Sodium carbonate 1 z Sodium sesquicarbonate 1 tD ~ 27 Propylene glycol Propylene glycol 1 01/11/73 t 4 02/19/74 PB-265 504 v 01 Propylene glycol monostearate 1 ~ 28 Glycyrrhha 01/11/73 12/19/74 N/R 04/08/75 PB-354 529 -1 Glycyrrhi tin 2 ~ Glycyrrhl:in, ammoniated 2 (D ~ b Licorice 2 H ~ r A 29 Capryllc acid 1 01/29/73 12/19/74 N/ R 04/08/75 PB-2S4 530 < ~ 30 Glycerides 02/0S/73 08/29/7S N/R 17/19/7S PB-3S4 536 Glycsrln 1 ~ R n Monoglycerldes glycerides of edi6;4; fats or olls or edible fat-forming fatty acids 1 Diglycerldes of edible fats or oils or edible fat-forming fatty acids 1 - Acetoolains 1 Acetostearins 1 ~ 0 Dlacetyl tartarlc acid esters of - ~ monoglycerldes 1 ~ ~Key: N/R = No requests recelved N ~ P t  Reports completed before Initiation of hearln8 procedures In 1974 14z tsV49
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42,316 INevr, Developments hydroxide, which4a published d el'sewhere in this issue of'the Federal 3'teg4ster.The requested deletion$com the proposed regulation of GGh1'p' maximum levels ofluse for adipic acid is therefore denbedL In 1964 an FDA official issued an opinion letter that recograized the GRAS status of sodium adipate as a buffer and neutcalizing,agent. However, the agency announced in the January 3011gR9 proposal (41' Flti 5905) that it' does not consider itself bound by the 1964 . opinion letter because it~ does not possess certaia, informa tion , tha tl in accordance with 1'170:35, i's required'iln order to affitm the,G'RAS status of sodium adipate.1n partieular, the agency is unaware of the manufacturing methods and food'-gcad'e specifieations for sodium adipate, the food categories in which it, Is used, and the usual-and maxi'mum use levels in each foodl category. Because ffiel'aclt of this i information prevents the effni'tion:of conditions of'safe use. FDA requested the submission of this information as comments on the proposall. No: comments onsodium adi'pate were. received inresponse to, the proposah Therefore, sodium adipate ie mot being affirmed as GRAS'by FDA: Future FDA approval!of sodium adipate maybe sought through the GRAS!or food additive petition pro cedurea outlined'in $170.35or117111(21CFR171:1)forany new use of this substance. Al'ternatively, an independent GRAS, determination may be made in accordance with J 170.30 (21 CFR 170130) l and'J1&4.1 for uses of sodium iadipate consistent with available safety: data~on this substance: The agency has determined under 21 CFR 25.24(d)(6) (proposed Deaember111, 1979.,44 FR 71742) that this action i're of a type that does not Individually or cumulatively have a significant impact 1019 7-6-82 on the human, environment Therefore, neither an environmental assessment nor an environmentallimpact statement is required:. . 1trt acoordance;with Executive Order, 12251, FD'A has carefully analyzed the economic effects of this rule, and, the agency has determined that; the rule is not a major rule as defined by that order. List of Subjects ' 21 ChR.Part 172 ( ( Food additives; Fbo&preservatives; Spices and flavorings. 21'CPR'Part'YB2 Generally recognized as safe (GRAS) food ingredients: Spices and flavorings. 21 CER Part 184. Dhrect food ingrediente; Food ingredfients; Generally recogaized as safe (GRAS) food' ingredients. Therefore, under the Federali Food.. Drag,,and Cosmetic Act (secs. 2A1(s)~, 409, M(a): 52 Stat.1i055, 72 Stat.1Z84- 1T88 as amendedi(M U.S.C. 321(4848, ! 371(a)))i andiund'er authoritp delegated `~ to the Commissioner ofFbod and'~ Droga. (21 CFtt' S.10), ParYs 172,182,' and 184 are amended as follows: * ~ * * * Effective d'ate. 'Phia regul'ation shall be effective July' 28,198Z NoterrIncorporation by reference approved by the Director of the Off"ice,oC the FederallRegister on May, 27,1982J and ib on file at the Office of the Federal Register, (Secs. 2An(s), 4a9. zoL(a)', 52 Stat. ioss, ri stsit. 176+L-1288 as amended (Z1iU.S.t;.321(s), ,358, s~(a)1l Datedi June 7. 1981 frViUiam F. Randolph`, Acting Associate Commissloner for RegulatorpAffairs. . ~ 142,,0;q,4 PROPYLENE GLYCOIl"S'GAAS STATUS'AFFIR'MED: Food and Drug Administration Order, published at 47 F.R. 278'10, June 25', 1982: Fropylene g)ycoll has been affirmed by the Food and Drug Administration as a generally recognized as safe direct food~ ingredient. However, because pro- pylene glycol monostearate isalready the subject of a foodladditive regulation, the agency has withdrawn the proposal to affirm the GRAS status of this subst'ance : to avoid redundancy and confusion. In response to comments, the 142,044 c019182, Commleree Clearing House, Inc.
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1019 7-6-82 New DeWelopments 42,317 maximum level of propylene glycol'in seasonings and flavorings was increased to 97 percent concentrations in which the finishedlfood product contains 2'per- cent and was increased in baked goods, in fats and oils, and in dairy: products in response to current usage information: A use level of 5 percent of propylene: glycol in nuts and nut products (including coconuts) i was added to the other GRASllfistingforthesubstance: See¶ 67,9'17:66 ( c [t)oaket N+a 77N-'!W2] 1 suMMARr; The Food and Drug tldminstrathon (FDA) iis affirming that propylene glycol is generally recognized as safe (GRAS) as a direct human food ingredient. However, FDA Is withdrawing the proposed GRAS affirinati'on of propylene gLycol monostearate as a direct food ingredient because this substance is already subject to a, foodladditiwe regulation. The safety of propylene glycoll and propylene glycol monostearate has beenn evaluated under the agency''s comprehensive revi'ew of substances considered ito be GRAS' or, subject to a prior sanction. EFFECTIVE DAIIE]ply 28,1982. FOR FWRTHEfl INFORMATION 6ONTAC7N John W. Gordon, Bureau of Foods (HFF- 335)~ Food' and'IDrug Administration, 200 .C St.,S1M1lf:, Washington; DLC, 202K 202- 4'28'-9483. SUPPLEMENTARY RrFORNtAinolC Tn the Federal Register of June 17.19" (42 FR 30865). FDA published a proposaUto affirm that propylene glycol and propylene glycol monostearate are GRAS for use as direct human food fngredients, and that propylene glycol ls also GRAS'as an indirect human food fngredient. The proposal was published ln accordance with the announced'FDA review of the safety: of GRAS and prior. sanctioned'f'ood ingredi'ents: In accordance with J 170.35 (21 CFR 170.35), copies of the scientific literature review on, propylene glycol and d'erivatives, reports of the teratogenic and! mutagenic sareening, tests for propylene glycol, and the report~ of the Select Committee on GRAS Subst'ances : (the Select Committee) on propylene, glycol and propylene glycol ~ monostearate are available for public review in the Doc&ets M'anagement Bronchi(HFA-oS), Food and Drug Administ'ration, Rm. 4-62, 560o Fishers Lane, Rockville, MD20957. Copies of Food Drug Cosmetic Law Reports these documents have also been made available for aublic purchase from the National 1lechnical~lnf'.ormation Service (NTIS) as indicated in the proposall In addition, a mutagenic study on propylene glycoll which was not listed in the proposaU i's available for public review in the Doclaets Management Branch (address above), and may be purchased ~ from NTIS (order No, PB 257- 868'/AS, price code A03'„ price $4.50);. 1bib study: did not' indicate that the public health would be adversely affected by the use of propylene glycol, as a GRAS food ingredient.t in add'ition to proposing to ~affirm the GRAS status of propylene giycol and propylene glycol monosteararoe, FDA gave public notice that~1't was unaryvaree of anyprior-sanctRoned food ingredient' use for these substances, other than for the proposed conditions of use. Persons 1 asserting additional or extended uses, in accordance with approvals granted by the tJLS. Department of Agriculture or FDA before September 8:1958; were given notice to submit proof of those sanctions, so that the safety of the prior- sanctioneduses couldThe determined. That notice was also an opportunity to, have prior-sanctioned uses of propylene glycol and propylene !glycoll monostearate recognized'by i'ssuance of an appropriate regulation under Part 181-Ptrior.-Sanctioned! Food' Ingredients (21 CFR Part 181) or affirmed as GRAS' under Part 184!or186'(21 CFR Parts 184., 186), as appropriate. FDA also gave notice that failure to ~ submit proof of an~applicable prior sanction in response to, the proposall would! constitute a waiver of'the right to, assert that sanction at any future time.. No, reports of prior-sanctioned uses for propylene glycol or propylene glycol monostearate were submitted in response to the proposal. 7rherefore,, in~ accordance with that proposal, any, right to~ assert~ a prior sanction for a use of propylene glycol under conditions 142,044
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42,318 New Devel'opmtents 1019 7-6-82 different from those set forthdn this regulation has been waived.. Fifteen comments were received In response to: the agency's proposal and supporting information on propylene glycol and propylene glycoli monostearate. A summary of the comments and the agency's responses follows: 1.'l~vo comments.asked whether a contradiction exists between the GR'AS afi"irmation for propylene.glycolll monostearate and the existiizg , reguliations 15172.858 (27I CFR' 172.85Bj:,on propylene glycoiimono- and diesters of ' fats and fattyac'idls. Several comments were alao received conceniing,methodsg of manufacture and!usage of propylene glgeol monostearate. Because of the ex'isti¢ig food additive regulation (21 CFR 172.858] for propylene glycol monostearate.the agency agrees that GRAS affirmationfor this ingredient would ereate, a redundancy and' eould'alao~ cause confusion. Consequentl y;, the agency is' withdrawing the proposal tp affirm propylene glyeot monostearate as GRAS, The current food additive regulation governs the uses of the substance reported'during,the surveyof food'~ manufacturers (6ondiicted by the National Academy of Sciences/National Research Council (NAS/1V&f;))'and during, the comment period on the proposal. 2. Three comments asserted that the . proposed maximum level of'10 percent for propylene gl'ycollin seasonings and flavorings was impractical landd requested that a higher use level be permitted in~thig food categary., As a commenYVointediout, even when the concentration of propylene glycol in a flavoring is 97 percent„ the concentration, of the substance consumed in the finiahed food iproductt is less then 2.01 percent; The agency agreea,witkt'he coman ents and concludes that the use of propylene glycol in flavorings only produces a small amouaofthe substance in the finished food as served. Processor . information available to the agency confirms the comment describedd above. Gonsequently,,the regulation has been modified', to~ incl'ude 1he current good' manufacturing practice (CGMP) 142,044 maximum level of use of~up to 97' percent propylene glycol in seasonings and flavorings. (I'he regul'ation has als6 been mod'd"ied' to in:clude a CG1tiP' maximum level of use of 2.0 percent for all' other foodicategories: This change is discussed below.)' 3. Three comments requested that additional food categories and levels of use be provided for propylene gly,cou. Two requests were foruse !of propylene glycol at a use level of'5 percent in coconut, and one requeawas for the use of the substance atl a level of 4 percent i'n~nuts and'nut products as defined'.by j 170.3(n)(32) (21GFR 170.3(w)(32}). The ageqey, has determinedithat there are adequate safety data to support the levels of usage for these additional food categories, and that these requests are appropriate: Therefore, the final rule has been modifled'to includ'e the use of propylene glycol~ at a GGW raaximumm level of use of 5 percent in nuts and nut products,, inciudiag,coconut: 4. Two ~comments stated that Prop7tlene,gl'xcol is used as a component of adhesives under j ',-175.10& (21 CFR 175:105) and requestedI that the proposed'~ regulation be modified to include the use of propylene glycol in adhesives under • ~' 188i1086' (21i Q+ '16&1888). . Because the use of GRAS substances, 'including propylene glycol', in adhesives is provided for in $175:105, the li'sting of propylene gly,col in Part 196, for use in adhesives is unnecessary. Gonsiatenf with its traditi'onal practice, >gI)A proposed originally to establish separate regwlations for propylene g>~yco1 in Parts 184 and 186 tioo govern its direct and indirecYGR'AS uses, respectively. Under $184.1(a) (21 GFIt 1841({s)), however,;ingredienrts, affirmed as GRAS for direct food use in Pgrt 184 are considered to be GRAS'far indirect uses without a: separate listing, in Part 188. Based on I 184.1(ak FDA hass rg,eonsidered its traditional practice and has concluded that the duplicative listing in~Part188'is unnecessary, as a generhl rule„ and may cause confusion.. Thus, unless safety considerations make it neeessaryto impose specific purity specifications or other restrictions on the indirect use of a GRAS substance. FDA will nor longer list in Part 186, (D 1982, CCommerce Clearing House, 7nc. C ( ( C
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c c C C 1Q19 7-6-82 . 9 New Developments 429319 substances that are affirmed as GRAS for direct use impart 184. In keeping, with this change in policy, FDA will not promulgate I 188.1888 a$ originally proposed'. The indirect uses of propylene glycol proposed for inclusion in. 1:188.1868 are authorized under J 184.1888 (21 CFR 184.1668) l and I 184.1(g), In the case of propylene glycoll FDA finds that the general requirements that . indirect GRAS ingredients be of a purity suitable for their intended use in accordence.with 11 1'70.30(H)(S) (21 CFR' 170.30(fi)(1)) and usedlin accordance vvith current good manufacturing - practice are suffidenYta ensure the safe use of this ing;edient Therefore. no specific purity, sspecifications are necessary for indirect use. Although the policies discussed in the two, preceding paragraphs are not: Inconsistent with the agency's current regul'ations, elsewhere in this lssue of the,ffederal Register the agency is publishi'ng, a proposal to amend Its procedural regulations in partb 184 and 188 to reflect dearl'y these polides. Addlti'onal 'iaformation from tbe NAS/ NRC ind'usthy' survey' regarding the ' current good manufaeturing, practi'ce maximum levels of use of propylene glycoll has been ~made available to, the agency since the publication of the June 1,7,1977 proposal`to 'affirm propylene . glycol as G12AS. This new informatlon indicates that the mazimum-CGUp reported'~ level I of use of propylene glycol has been; increased to 1l5 percent in, baked!goods andin fats and oils and 2.5 percent in~ fiozen dairy products. The proposedCGMp maximumlevel of use of propyl6ne 'tdlycol in baked goods, fats and', oils, and frozen dairy products ian the proposed regulhtioa.vas 1A; 0A8, and 0.8 percent. respectively. Because FDA has stated that the GRAS affirmations will reflect the conditions of use that eturentiy, exist or that are reasonably foreseeable (99' FR' g4'1i94; 34195; 'September 23. 19T4); the final regulation has been revised to refdectt this new usage 3nformatiom The f[nal I regulation as revised'~ states that under current good manufacturing practice the maximum, levels of use of propylene glycol in frozen, dairy products ih 2.5' Food' Drug Cosmetic Law Reports percent and in "all'other food categories" is 2.0 percent (see the agency''s response to comment 2 above concerning flavo;iags). The bakedlgood's and fats andloils food categories have been eliminated'because they are now under "all other food' categories." Because the use of propylene glycol as a color was reportediby the NAS/14RC Industry survey, the proposed regul'ati'on listed the technical functional effect of' the ingredi'ent as a color and coloring, adjunct, as defined in I 170.9(o)(4)(21' CFR' 170:9(o)(4'))'. The agency has determi'aed: hovvever, thattbe listing, of GRASlihVedlents for di'rrect!use in food as colorants ia imappropri'ate because the evaluation of ingrediente for direct eolor use Is properly the subject of colorr additive regulations. Acsordingly. FDA has removed the Rati'ng, of propylene glycoll for use as a ~ color and col'oriag adjunct from the finai regidhtionl The use of propylene glycol as a color diltrent Is permitted'und'er the existing color additive regulatdon 1(21 CFR 73.1(a)), whir.h provides for the use of GttA3, Ingredients as diluents ia, color additive mixtures for foodiuse exempt from cerl3ficatlonlI~.'owever. the GRAS affirmation.proposal d'id! not list a technical lfunctional effect that would cover this use. To, accommodate this use, the fiaal rule has been modified to lnelude use of the ingredient in food as a processing,aid as defined by g' 17019(0)(24): The ageacy: has determined under 21 CFR 25.24(irl)(8) (proposed~December 11.. 1979; 44 FR 71742) that this action i'® of a type that~ does notindividuallx, or cumulatively have a, significant impact on the human environment Therefore., neither an envimnmental'.assessment nor an environmental innpact statement is requiredL In accordance with Executive Order 12291; FDA has carefully analyzed the economic effects of 'this rule, and the agency has determined that the rule Is not a major rule as defined by the Ord'en, Ia'st of' Subjects 21' CFR Part 182 Generally recognized as safe (GRAS) i food ingredients; Spices and flhvorings. . 142,044
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42,,320, New Developments 21 GFR: Part 184 Direct food itigrediente;: Food ingredients; Generally recognized as safe {GRAS) food ingredients.. 1lierefore. under the Federal Food, Drug, and Cosmetic Act (secs. 20d(s), 409; 701(a), 52 Stat. io55, 72$tatt 1784- 1788 as amendedl(Z1 U.S.C.' 321(s), 34'8;. 371(a)'))', andlunder, autliorityrdelegated to the Commissioner of Food and Drugs (21 CFR 5.10), parts 182 andi 184 are amended as follows: 11014 7fi-82 F.fAectivre date:'t'his regulhtion is effective on jhily 28.1952. Nate.-Inoorporation by reference approved by the Dteector of the Office of the Feder@! Regtster'oniWfarah 31,1982, and is onn file at the Uffice of the Federel Register. (6ecs. 2o1(a)r 409: 7o1(ak 52 Stat 1033, 728tat 17841-1788 as amended (2LUaG. 321(sj, 54& . 371(a)1) IDated: June 7, i9B2. wllliam F. Rendolpli, , ActftrgAssociate Commirsioner for RegvlcaaryAfJ°,airar. 1;42,045GRAS STATUS OF ACETIC ACID, SODIUM ACETATE„SaDiUM DIACETATE AFIF(IRMEDi Food and Drug Administration Order, published at 47 F.R. 27813, June 25, 1982'. The generally recognized as safe status of acetic acidl, sodium acetate, and d sodium~ diacetate for use in human food' has been, affirmed by the Food and Drug AdntiQUstration. The agency did not affirm the GRAS status of amn- monium acetate due to a lack of informationregarding its use, manufacturing, procedure, or specifications: Ma2rimumn use levels for acetic acid were increased in cheese and dairy product analogs and were added for chewing gum and boiler, water, as were maximum use levels for sodium .acetate in hard~ cand'y.. Acetic acid content must be declared in labelfing,and may not be substituted for vinegar in pickled food'. The FDA"s responses to comments on the proposal! are incIuded' in the preaffible to the fimal order, reproduced bellow.See ¶ 57,,911.5; 57,918.21; 57;J18,54 [modtef Nb. 7reMt-030o 1 ' sumtAAmR:-The Food and~Dw,g, Adiministration~(FDA) iis affirming that; acetic acidi, sodium acetate„and sodiumm diacetate are generally recognized as safe (GRAS) ias direct human food ingredients. It is a1so not affirming the G&AS!status of ammonium acetate; because there is no usage information concerning this substance. The safety of ' these ingced'ients has been evaluated', under the comprehensive safetX review being conducted by the agency. t FMemE'wtTIC lWY 26,19M FOR FIWITMER RtFOaslATtoN ¢oNTAC11: Corbin L 14Ii1ea Bureau of Foods (HFF- 335), Food and Drug Administration, 200 C St. SW., Washington. DC'20204, 202- 4'72-4750. suPKSMFWARV' WottuATtote Itr the Federal Register of Apri13; 1978 (4'4 FR 19430). FDA published a proposal to affirm that acetic acid, sodium, acetate; and sodium, diacetate are GRAS for use as direct human, food ingredients. 142,045 Ad'ditionally: FDA proposed'that ammonium, acetate be removed'from GRAS'status because there is no information that it is currentDy being used'im1foodl The proposal'was published in accord'ance with thee annbunced FDA review of the safety of GRAS and lpriar-sanattoned foodi©gredtents: In accordance with 1170:35 (21 CF1[' 17035)L copies of the scientific literature review of acetic aciid, sodium acetat'e,, sodi'um diacetate; and ammoni'um, acetate, reports of the mutagenic and I teratogenic tests for each imgredient, and the report of the Select Committee on GRAS Substances (the Select Committee)I are available for publicc review in the Dockets Management Branch (FfFAr305). Food and Drug gdministration. Rm. 4-8Z 5800 Fishers Lane, Roclkvi(le; MD 20857. Copies of these documents also are available for public purchase from the National Technical Informathon Seivice as~ announced!isi~the proposal. (D 1982, Commerce Clearing House, Inc. ( C ( c
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56,986 Pbod' Additives 10114 6-1-82 (.{lft~t of '. Rld U.rl al0ef.r ).'1MPlinhalMR' Ricebran oil, sulfated, ammoniumj potassium, orsodiumsalt. Rosinsandros_i¢derivatives'___"-__________________'__'____ Aaprorided'ins1;8.3B70of:thischapter: Si lica _ ----~--°--------------------'---------'--'-------'-' . SodiumForttseasprenervatiPeofdefoameronly. SodiumFentachlomphenate------- _-------------------- -__.. For.useaspreservativeofdefoameronly.Sodium'trich']mrophenate-------------------------------- , Foruseaspreservativeof'de7oaTneronly. Sperm oil, sulfated, ammanium,, potassium, orr sodium: , salt. . - ~ - - Stearyl.alcohol__,__.-____-_,_______.----_.__.__._________.__-.__._-. . . Tallbil.fattY.acids~~-------------------~----------------'--'--' Tallowfatty~acids,hydrogenated.orsulfated_____________, ~ Tallow, sulfated, ammonium„potassi~um, or~sodium salt_, Triethanolamir.e---------'-------~-------'---------'-------'--' . Triisopropanolamine-._'----------------'----------------~-•~ .. . . ~ Waxes, petrolettm--------°-------------'--------------'--'--~. . (e) The defoaming agents are used' as follows: (1) The' quantity of defoaming agent or agents used shall not excee3' the amount reasonably required to accom- plish the intended effect', wliich is to pre- vent or control' the formation~of' f'oam. (2) The defoaming agents are used in' the preparation and application of' coat- ings for paper and paperboard. [As' amended,, 47' F.R. 21239', May 18', 1982'. ] I [1f56,,968] § 17&2!110! IDtfoamimg agents used in, the manufacture of pap:e='and'paper- boardl Defoaming agents may be safely used 1'n the manufactilre of paper and paper- board intended for use in packaging, transporting, or'holding foodiin accord- ance with the following: prescribed con- ditions:: (a) Tlie defoaming agents are pre- pared from one or more of the substances named in paragraph, (d)' of this sect'ion,, sub3ect to any prescribed limitations. (b) TThe defoauling agents are used too prevent or control' the formation of'foam, during the manuf'acture of paper andl paperboard' prior' to and during thee sheeti-forming process. (c) The quantity of defoaming agent or agents addcd'. during the manufac- turing prccess shall not exceed the amount necessary to accomplish the ir1- tended technical effect. (d) 1 Substances permitted to be used i in' the formulation of defoaming agents in- clude substances subject~ to prior sanc- tions or approval, for suchi use and em, ployed sub,jeet to the conditions of'such sanctions or approval8, substances gen- erally recognized as safe far'use In food, substances generaily recogni_.rv as safe for use,in paper and paperboard, andi substances listed In this paragraph, sub- ject to the lirnitations,,i2' any, preseribed. 156,968 21 CER 176.210. (1) Fatty triBlycerides, andi the fatty acids, alcohols, and dimers derived therefrom: Bee1'tallow: bTustardseed oil. Castor oil. Palm oil.. Coconut'oil. Peanut oil. Cornioll'. Rapeseed oil. Cottonseed oil. Ricebran oil'. Flah oil. , Se yhean oil. Lard oil. Sperm oil. Linseed oil. -Tall oil. (2) Fatty triglycerides;, and' marine oiLs,, and the fatty acids and'l alcohols derived therefrom (paragraph (d) (1) of' this section) reacted!with one or more of' the followiilg; with or without dehydra- tion, to formi cliemiaals' of the category indicatedin parentheses: Aluminum hydroxide (soaps)'. Amrnonia (gmtdes).' Butanol' (eaters) Butoxy-polyoxypropylene, molecular weight'. 1,000-2.b0o (esters).. Butylene glycol (esters). Calcium hydroxide (soaps) Diethanolamine (amides) ~ Dietifylene glycol (esters). Ethylene glycol (esters),.. Ethylene oxidd (esters and ethers). Glycerin (mono- and dhlycerides):. Hydrogen (hydrogenatedcompounda). Hydrogen (amines). Isobutanol (es,era)1. Isopropano1, ( esters) . Magnesium hydroxide (soaps).. Methanol (esters). Morpholine (soaps). . Oxygen (alr-blownoils). Pentaerythrltal(esters). Polyoxyet'hylene, molecular weights 200, 300., 400; 600, 700; 1L000.,1.540L 1,680, 11,780,,4;600 (esters)'_ Polyoxypropylene, molecular weight 200- 2.000 (esters). . Potassfum'hydroxid'e (soaps). ilkopanol (est.ers). Propylenee glycol, (esters) ~ Propylene oxide (esters). 4odium,hydrextde(soaps). SdrWitol (esters). Eulfuric acid, (Sulfated and suifonated com- pounds)~. T7ietban ol'am hte . ( amides. and soaps ). 'IYlsopropanolamihe (atnides and soaps). Trimethyl,oletha^e (etters.),. Zinc hydroxide (soaps). Qc :1982, CCommerce Clearing,ll'ouse, Inc. ( c
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1120 6-4- 8++ Carponents of cx3tirlgS 56,909 C C C appendix )(;1.I(ASTIwf inethod 1)1243- 79, "Standard Test Method forLilute Solution Viscosity of Viny1't;hloride Polymers," vvhich is incorporated by reference;,seeparagraph (b) of 'this i seciion for availability: of the incorporation by reference) vaith, the redoeed viscosity determined for three concentration levels not greater than 0.5 gram per deciliter and extrapol'ated to Aro concenttation for intrinsic viscosity. . The following formula is used for determining re- dueed viscosity: Reduced viscosity in terms of deciliters per gram- toxe. Where: t=Solution efflux, time. to=Sol'vent ef'flu'x~timex a=Concentration of' sol'ution in tenns' of grams per deciliter. [As amend'ed, 47 F.R. 11839', Mar. 19, 19'82'a 49 F.R. 10087, Mar. 19,, 1984.] [ 95~6, 895 ], g175:300 yl;tsinous and polymeri¢ coat, ings. Resinous and polymeric coatings may be safely used as'the food-contact surface of articles intend'ed~ for use in producing, manufacturing. paclting. processing. preparing, treating.paclc- agang,, transporting, or holding food, in accordance with, the following pre- scribed conditions: (a) The coating is applied as a con- tinuous filtn or enamel over a metal substrate, or the: coating is intended for repeated food'-contact use and' is applied: to any suitable substrate as a continuous film or enamel that serves, as a functional barrier between t'he food and the substrate. The coating iss characterized by one or more of' thee following descriptions: (T): Coatings cured'~ by'oxidat3on: a (2)' Coatings; cured by poi'ymeriza- tion, condensation. and1or cross-1'ink- ing without oxidation. (3) CoatingS prepared' from prepoly- merized substances. . (b) The coatings are formulated from optional substances that may in- clude:' Food Drug ; Cosmetic Law Reports (1) Sabstances generally recognized as safe in food. (2) Substia.nces the use of which is' permitted by regulati'ons in this part or which are permitted by prior sanc- tion or approval and empl'oyed under the specific conditions, if' any, of the prior sanction or approval. (3) Any substance employed! in' the production of resinous and polymeric coatings that is. the subject of a regu- lation in Sti'bchapter B of this chapter and' conforms with any specification in such, regulation. Substances i named in this paragraph (b)(3) and Psrther identified as requiredf (i) ~ Drying oils, includi'ng the trigly- cerides or fatty acids derived there+ from: Beechnut: Candlenut. Castor (including dehydrated). Chinawood (tung). Coconut. Corn. Cottonseed. Fish (refined). Hempseed. lanseed. Oiticica. Peri1[a., Poppyaeed. Pumpkinseed. Safilower. Sesame. Soybean. Sunflower. Tall oil. Walnut. The oils may' be raw, lieat-bodied, orr blowni They may be refined by fil'tira- tion+ degumming. acid or' alCkali, wash, ing, bleaching, d'istillation., partial de- hydration, partial polymerizat'ion, or solvent ext'raetions or modified by combination with maleiie anhydride. (ii) Reconstituted oil5 from triglycer- ides or fatty acids derived from the oils listed in paragraph (b)(3)(i) of this section, to form esters with:: Butylene glycol. Ethylene glycol. Pentaerythritol. Polyethylene glycoh Pol ypropylene , glycol. . Propyl'ene glycoL Sarbitol. Trimethylol ethane. Trimethylol , propane. (iii) Synthetic drying oils, as the basic polymer: Butadiene and methylstyrene eopolymer: 21 CM 175'.,300, 1(56R895.
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( C c c 1137 10-1-84 Ccunpolle.nts 1.4'130-1.4190: for use as a modifier for nylon resins complying with § 177.,1500 of this chapter and'for phenolic and epoxy resins listed in paragraph (b)(3) (vi)' and (viii)'of this section. respectively, at a levell not to exceed ll5 percenti of' the coating.. 2-Ethylhexyli aerylate-methyl! methacrylate- acrylic acid' copolymers for use only as modifiers for epoxy resins listed' in para- graph (bX3XViii) of this section. Methacrylic acid and the following esters thereof: ButyG Ethyl. Methyl. Methacrylic acid or its ethyll and methyl esters copolymerized with, one or more of the following: Acrylic acidL Ethyl acrylate. Methyl acrylate: n-Buty1 acryli<te-styrene-methacrylic acid- hydroxyethyl methacrylate copolymers containing no more than 2 weight' percent of totalipolymer units derived from, methr acrylic acid' and i eontaining, no more than 9.5 weiglht' percent of total polymer units derived from hydroxethyt methacryl>rte7 for use only in coatings in, contaeG with dty, food (food type VIII',in table I of para. graph (:d) of' this section). 2-(Dimethyla- mino) etlianol (C.A.S. Registry No. 108- 01-0) may be employed,as an optional ad- Juvant', substance limited'tio no more than 2 weight percent based on, polymer solids in the coating emulsion. (xxi) Rlastomers, as t!he basic poly- mer: Butadiene-acrylonitrile copolymer. Butadiene-acrylonitrile-styrene copolymer. Butadiene-styrene copolymer. Butyll rubber. Chlorinated rubber., 2-Chloro-1'.3-butadiene (neoprene). Natural, rubber (natural latex or natural latex solids, smoked or unsmoked). Polyisobutylene. Rubber hydrochloride. Styrene-isobutylene copolymer. (xxii)I Driers made by reaction of' a metal' from paragraph (b)(Uxxii)(a) of' this section with acid, to form the salt listedi in paragraph, (b)(3D(xxii)(b) of this section:. (a) Metals: Aluminum- Calcium. Cerium. Cobalt. Iron,. Lithium, M'agnesium. ManRanese. Zinc. Zirconium, Food IDrug Cosmetic Law Reports , of Coatirlgs. 56, 91.1-5 : (b) Salts:. Caprate: , Caprylate. I'sodecanoate_ Linoleate., Naphthenate. Neod'ecanoate: Ootoate (2-ethylhexoate). Oleate. Palmitate. Resinate. Ricinoleate. Soyate.. Stearate.. Tallate. (xxiii ) W'axes: Paraffin, Type I., Paraffin. Type II. Polyethylene. Sperm oil'. Spermaceti. (xxiv) Plasticizers:~ Acetyl, tributyl icitrate. Acetyl triethyl citrate. Butyl phthalyl butyl glycolate:. Butyl stearate. p+derl-Butyl phenyl salicyl>ate. Dibutylsebacate. Diethyl' ptithalate. Diisobatyl adipate. Diisooctyl~ phthalate. Epoxidized soybean, oil (iodine number maximum 14,: oxirane oxs-Ren content 61, minimum), as the basic polymer. Ethyl phthalNl ethyl, glycolate. 2•Ethylhexyl diphenyl phosphate. di-2-Ethylhexyi, phthalate. Glycerol. Glyceryl monooleate. Glyceryt,triacetate. Monoisopropyl citrate. Propylene glycol. Sorbitol. Mono~. di-., and tristearyl citlrate. Triethyl citrate. Triethylene glycol. 3(2-Xenoxyl)-1',2-epoxypropane. (xxv) Release agents, as the basic -.polymer„ when applicable: M,, N`-Diol'eoylethylene'diamine (CAS Reg. hio:11©-31-6), for use only' inn ionomeric resins complying with ¢ 177:1330'i of this chapter and in ethylene vinyl acetate copolymers complying with, 11y7.1350 oflthis chapter at a level noti to exceedAQ085 milligratn per square centimeter (0.055 milligram per square inch), in the finished'fiaod-cont!act' article. lW.ly"'-Distearoyl ethylenediamine. Linoleic aoid amide: Oleic acid'amide. 21 CFR 175.300 156,895 '
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C C 1161 3-18-85 CcupOI'1entS of Codt1.1Rf3s' livering:l9VF=20V F waterandibent so astodirect a'stream of water upward. FrEssure, cooker. 21-quart capacity with pressure gagey safety released and removablee rack., 12.5' Inches inside diameter x: LL' inches Inside height. 20 pounds per square inch safe operating pressure. Qven. mechanical convection: range to in- clude 12q' F-212'' F explosion-proof. Inside dimensions (minimum). 197 x 19" x 19'e. constant temperature to z2'' F(AVater bath may be substituted). Incubator. Inside dimensions (mimitnum) 19" x 119" x 19" for use at 100*' Ft2*' F ex- plosion , proof (water bath may be substitut, ed)L. Constant-t'emperature', room or chamber 70' F±2• F minimum inside dimensilons i 19" x 19" x 19". Hot pl'ate. nonsparking (explosion proof):, top' 12" x 20". 2.S00:watts0 with: temperature control. Plstinum, d1s11, 100-milliliter' capacity minimum. , All alass. Pyrex or equivalent. (2) Reapent's. .. Water,, alli water used! in exttaction proce- dure should I be freshly demineralized (deionized) di'stilled' water. lieptane. reagent grade., freshly redistilled' before use, usine only material' tloiling at208*' F:, AlcohoL 8 percent (by'volumeh, prepared from undenatured 95,per¢enU ethyl alcohol,l diluted with demineralized i or dist'illed i water. Chloroform reagent grade. freshdy redis- tilled before use. or a grade having an'estab- 13shedn consistently low blank. Filter paper„ Whatman No. 41 or, e4uivra- 1ent. (g)! In accordance with good'~ manu- faettu'ing practir:e. finished coatings intended for repeated f'oodlcontaet use shalli be thoroughly cleansed prior to their first use In contact with food. (h)! Acrylonitrile copolymers identi- fied in this section shall comply with the provisions of g' 180.22 of this chap- tert ua a .wa.ne.. (s a.si,.Ma pa,imm Atayib.eid pmlym.r ard ft .aryl of mWtyl aetara_.__..... Aaylimid. aopotynwizad wioh.. NAyI ia-yla/e ard/m aty-r.no rdfar metli.uyfic aci0,L andthe . copokrtasr aspLuntly'n.cwd witli forrtWCSfydeand. buunmt tik"ta.om 8utyl nft.r ._...,_..__....__.._.......__.... MN' '. ... . .._._.„.........__.Y._....__. For we only~ as aqmlymar¢aoniiiMrbifot n 2-wMmstbyl metluaryWe. sodun arq.l 2-EtlyM.,l~ aoYrM.oopaymwaW with ~on.anwca o/ Vn 16NOwk ~ . ACrykXVb**'- ----_-_ 'I [The next page is 56 r 9'21-3. ] Food Drug Cosmetic Law Reports ~ 561921 [i21 CFR 175.300 as of Ap. 1,, 1983';' amended, 48I F.R. 44203, Sept. 28, 1983; 48'F.R. 56745, Dec. 23,1 1983;' corrected, 4'9'. Fl.R';., 574'8, Feb. .15, 1984;, amended, 49 F'.R. 10087„ Pfar. 19, 1984; 49 F.R. 13138, Apr. 3,, 1984; 49 F.R. 36496, Sept. 18, 1984; 50 F.R. 1500„ Jan-Il1, 1985'.] [156,,897] § 175.3'20' Resinous and.polymeric coatings for polyolpfi'n films: Resinous i and, polymeric coatings may'be safely used as the food,contact surface of'artieles intendedifor use in producing., manuIIacturing. packing, processing, preparing, treating. pack aging„transporting, or holding food. in accordance with the following pre- scribed cond'Ytions:. (a). Tlie coating i's applied as a, con. tinuous film1 over' one or both sides of abase film produced'from, one'or more of the basic olefin polymers complying with #'177.1520 of this, chapter. T'he: base polyol'efin film may contiain op- tional', adjuvant substances permitted' for use in palyolefin' fi'ltn by' applicable regulations in Parts 170, through 1899 of this chapter.. (b) The coatings are Ilormulatedfrwwm opti'ona)' substances which are:, (1) Substanees generall'y recognized' as safe for use iat or on food. (2) Substances the use of which is permittediunder applicable regu'lations in Parts 170 through 189 of' this' chap- ter., by prior sanctions. or approvals: (3) Substances identified in, this paragraph (b)(3)' and subject to, such limitations as are provided: 21 CFR 175. 320 156,897
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56,922 FoOdi Adclitives Uatw st,uawrcas .. P"t"m aW&wft1:3.-BtAylena ~pyk,d_...-.-.___._------------ ----- __..-...... Diethylane qlycnl 1........................................ -_......... 2:2-Gm.tDIy1-~ 1.8-prop.rr.aia ................................ Glylaero6...... »._.... __..... __ ._._-._........... _._-..... PtaAYIaIM 4h w Tf:mlhyWl Whns TtYna6fyloi pG~uw_....._~ .............._._.____.._._... f.nitatqms ~~. ]ll13 7 10-1- 84 ~F6r uwa ~, uryiy ~ az ~ a~ ptinn.r ~.ubcoat~ b andW '.potay ~ alalaa.. I d0attnps to the liase. atNBll ^"y°T' '°__...»».~....._._...._.. _r._.._.._..._..-....y ~~ CIM ~ dlde ~ .....•• .. .•_......... __•...._..r.._._._....._._.... ....II styret» wpdt!ma¢.a witM one or mae of the /oMbwhf~ Tewpene reiiins aamisting, ot ~ polymst'a a a,prene. B- pneure. anddoa dipentanei . addvaM+e leas than 5'~ arportilKauon nrnitiar M"e,tNun 5, and vqlbr lewthan 4, on tha Gardner: scale as arreuad n 50 patoent nwrerN ap:ilgfoMi6oh. 2-Sunmetlql I mefaaylate, aod.le . sstt ~ GbmicMAbatracts'. Service:No- 16C)4>87 -17: KrryA: chlanide•aaetete. M&Mq-~OddW ODPOh'°aW M . mdeie a'dd:anodiGaidaopotymer: Ywql chl0fidse cop0lymaaedd with Oos . amore. of ' Oro . idbwRtg YsrryiOeKie >f'mytiamsahilafda aopokrnwmsdd with ona «~ mam i o(' tMe.falbwirg: kcrylic'.ft acid anAife mNNyq atlry/: po{yM, , txay(, or ocM OS"rs: kcrylonitriMa-. ...-- AAbthaaylib acidandib metllyi; etfA prapyl.i Oulyl. aacto estera. , -vwnyl~aAOrba______ _~.-._....._.__.._._ (N7'~Plshcizen: Acatyf Watyl dtrate--......._-_-.-__.._.___.»..»._._......._»... DisnM 2-EtttypnsxO! dphenyt~ Ethyf phthdyl' etUyk yhrcdate •_- .••_-------------- _..-.-.•.•••_ Ghpcerol hiaKetaa (r1.Adjlrvants yeleisee ayierret, wazea. ~and i6apeKSarN.+1= Acetoma_....•...._..-..•._._..-»_.........__»._____._.....-•.-._._...... Amidea. (wqutmtiWteM of taty, adda tram vegetable . a' arwryf oiks:, n-Bm1yl' acef e1e ....................... _._..._.-.._................ ............... ..... n-f3uM' alcdnol...---...._.._»._,... .... .............................. _.... CandeW Ih wa:...__..-_.._..... _............................................. ... Carnauba wax..._...... ............................... .... _.. -................. _.. N.N'-Diokoyfcihrknediamimc (CASReg, Wo..l 10-31-6) , forr use only in ionomvic resinrs complying, with 4177.1330 q oflthlis chapter and in ethykne:vinyl aceute cvpooymencomplydng~ wit h.4177'.1350 of this chapter at ~a, . level not to enceed 0.00g5 . m~illigram per,square centimaer (0.055 milligramper spuare inch) in ihe . finixheA (bodYomaet anidle. - For.us!e.ady'in copolymer~coa.qs:under cond-Aidrs.ol'use. E. F. and G i desubsd I in Table 2 of 4',176:17q(c) pf ' ths' i chapter and MrniFxld to use, at a fevel nod lo exceed 2.0 peraant'Dyweght',of 1nedy'aopolyrner catlnp.. ., 1156, 897 21 C:FR 175.320 L~--__Iiw cO 19841, Commerce Clearing House, Inc. N
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1183 8-12-85 Gcxlq?onents--Repeated! Use Articles 57r123-5 1 ceroen aeak W.r" vm eaa): DieNmaceoua ~eert0 .................. Gtase fimsr....._......................... Mi¢a.......... .......... ................. .. C/xdilC:ar;iC:..... .................... Zin¢: steraN......_._._.........--~ Foru.e n cu.wnp eprw Fotue. p c.talyet.. Foruw tl M)biiceort: (c) The finished food1contact artirle,, when extracted with distilled water at reflux temperature for 2 hours, using a volume-to-surface ratio 1 of' 2 millill- ters of' distilled water persquare inch of surface tested. shall' meet the ! fol- lowing extractives limitatibns:. (1) Total extractives not,to exceed 0.15 milligram per square inch of fmod- contact surface., (2) Extracted phenol not to exceed 0.005 milligaaat~ per square i'nch of food-contacb surface. (3) No, extracted a.niline ~ when 1 tested by a spectrophotometric method sensi- tive to 0.006 mil'ligrarn of aniline per- square i'nclii of food,contact surf'aee:, (d)~ In accordance with good! mantl' facturing practice, finished molded ar- ticles containing the phenolic resins shail' be thoroughly cleansed prior, too their first use in contact with food, [11157',04'7'.2'1 C § 177:2420 Pbi)rester resins, cross-linked. Cross-linked polyester resins may be safely used as ~ articles or, components of' articles intended i for repeated' use in contact with, food, ini accordance withi the folllawing,preseribed conditions: (a) The cross-linked po1!yester resins are producedd by the condensation: of one or more of acids listed i'n, para- graph, (a)(1) of this section with one or more of'the alcohols or epoxides listed icti paragTaph~ (a)(2) of' this section6 fol- lowed! by copolymerizatiion with one or more of the cross-linking agents listed in, paragraph (a)(34 of'this section: (1) Acids:, . Li.l of' aubstamcae . Adipic. Fatty acids. and dimers thereof, from: natu- ral'sources. R'umaric. Isophthalic. Maleic. Methacrylic. Orthophthalic. Sebacic. Terephthalic. Zrimellltlc. (2)Bolyols and!poi'yepoxides: Butylene glycoll Diethylene glycol. 2,2-Dimethyl=1.3-propanedioL Dipropylene glycoll. Ethylene glycoli C}lyceroU 4;4' - Isopropyli'detediphenol - epichlorohy- drin. Mannitol: a-Methyl 1 glhieaslde. Peptaerythrltoli Polyoxypropylene. ethers of' 3.4'-isopropy- lide-nediphenol!(containing an acerage of' 2-7L& moles of propylene oxide ): 1Propyliene,giycol. Sorbitiol.. Trimethylbl ethane. Trimethylbl': p ropane: . 2.214-Trimethyl' .1.3-pentanediol. (3 ) Cross-linking agents: Butyl acrylate. Butyl methacrylate: Ethyl acrylate. Ethylhexyl acrylate: Methyl acryl'ate. Methyl methacrylate. Styrene. Triglycidylisocyanurate . (CA'S Reg., No. 245142-91)'. for use only ih coatings con- tacting bulk quantities of dry food': of bhie type identified in ;' 176.170(c) of this chap- ter, Table 1;under type VIII. Vinyl toluene. (b)I Optional adjuvant substances employed to facilitate the productiom of the resins or added thereto t'oo impart desired technical or physicall properties include the following., pro- vided thatl the quantity used does not exceed that reasonably required,to ac- complish the intended physical or technical ef'fect! and does not exceedi any limitations prescribed'in this sec- tion:' L.imilelior&(imits d'add6mn eVoened es D.~- by wdplltof r.:aMSd rerin) . 1. Wbitlom B K a a q Ur . : .... _ ........ - - - - -' - - . ..................... .................. . . . . . . . . 1wt-" . ca.Khol _......... _.... _...... _ ............................................ T&q'__.........._.._ .............._.__...... _..-................. .......-......... Oi;MAbutyl~ hyoru0urwme ..... _._ ................................................. C Hydrop 'rrorr.... ........ _..._.......... . .._........... - ................................. 2.: AooN.raWns: .. Baruyl u!wnstbyl amrorwm cMorid. ........... -........................... TaAal'rrot to ~euceed0:08 . percent . 0.01 peraen[ Totd notlo exceed.1.5.percant '0.05 percent... . C.ICiiem nePlttli.neN:...__ ............._.._........................_.............. Food Drug Cosmetic ll;aw, Reports 21 (F'Pt 177'. 2420 157,047.2 ~ ~ ~ ~
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1154 1-28-85 CaqpnEn{s-Pppeatej Use Artic1PS' 57,131 a hearing is held; failure to inclind'e sach ~ a description and'' analyais for any particular objection shall conslit'nte a i waiver of the right to a hearing on the : ( c L 0177:2600 Rubber artides inteaded for re- objeetion, Three copies of a11'dn(auaents shallibe subnritted and'shal'l be', identified, with the docket number found in brackets in the heading of tliiss regulathon. Received o3ijections may be seen in the office above between 9 a.mm and.4 p.m.. tHrnnmh 1Fridav.-. [As added, 49 F.Et. 49448, Dec., 20, 1984.]'' [ 1G57', 049 ]I Pested nse. Rubber arti'cies intended for repeat- ed use may be safely used' in produe-irtg. nnanufacturirtg: packing. process- ing., preparing, treating, packaging. transporting,, or holding food, subject to the provisions of thissectinn. (a) The rubber articles;are Prepared from natural and/Or synthetic pol'y- mers and adjuvant substances as de- scribed in paragraph (0 of' this sec- tion. (b) The quantity of' any substance' employed in the production of rubber articles intended for repeated use shall not exceed the amount reasonably re- quired to accomplish the int,ended' effect in, the rubber article and shall' not be intended to accomplish any effect in food.. (c) SUbstances employed in~the prep-• aration of rubber articles include the following, subject to any ldrnit,ations prescribed: (1i) Substances generally recognized as safe for use in i food or food packag- ing_ (2)' Substances usedl in accordance with the provisions of a prior sanetaon or approvall (3) Substances that by regulatiion in Parts 170' through 189 of ' this chapter may: be safely used in rubber articles, sub ject' to the provisions of' suehaegu-,, lation. (4) Substances identified in this paragraph (cX4), provided that any substance that is'the subject of' a regU+ lation in Parts 174, 175, 176. , 177;, 178 and ;, 179:45 of ' this chapter conforms with any specification in such~ regula- tion. (t)! Elastomers. Acrylonitrile-butadlene copolymer., FoodiD'rug Cosmetic Law Reports But4dene-acrylonitdle-ethylene glycol dl- methacrylate oopolymers contatning not more than S weight percent of, polymer units derived from ethylene glycol di. Ru~~lonitrile-methacrylic addioo- polyaier: BUtadlene-stytane-methaarqlic; acid eopoly- mer. ChloroPrene polYmers. 6hlorotatfluoroethylene-vinylldene fluoride eopolymer. EChylene-propylene copoi'ymer elastomers whir.h, may contain not more than 5 weiaMtLpereeent of'total polymer units de- rtaed from, B.methylene-a-norbornene andYor bethylldlne-1-norbarnene. Ethylene-pmpykne-dlcyelopentadiene eo:- polymer: Rthylene-ProPylene-1„4-hexadiene capoly- ®ers contatnina' no more than 8 weight Percent of total polymer units derived, from 1,4-heiadiene: Isobutylietae*iaoprene copolymer. Polybutadiene: Polyester eLsWmers' derived : from the reac. tion of diYuethyL terephthalate, 1,4-butan- edibl, kyd a-hydro:-omepa- hydroxypoly(oxytetrametliylene); for use oniX' Ih~ contact with foods containing not more than 8 percent alcohol and, llmited, to use in conxact with food' at, tempera- tures not exceeding 150' F. , Polylsoprene: Polyurethane resins derived irtom,reaetaons of diphenylmethane diiBocKanate with adip(c,acid and 1,4-butanediol. Rubber., naturaL Siiicone'basic polymer as described'in, pLSTNTmethod DL41841, "Standard.. Practice for Rubber and Rubber Gatices-Nomenclature," which is incorporated by reference. Copies may be obtained from the American~Societ+y for Testing M'aterials,1916 Race SL, Philadel'phia. PA 19105, or may be examinedlatthe Office ofltheEed'erali Register;,1100 L St: NVId'., V1Vashington., DIC. 20408, Silicone (SiD elastomers containing methyl groups= Silicone (Psi) elastomers containing methyl and phenyl,groups. Silicone (V'st) elastomers eontaining, methyl i and i vimyl groups. , Silicone (PSi) elastomens containing methyl and fluorine groups.. Silicone (PVsiY elastomers containing phenyl: methyl„ and vinyl groups. Styrene-butadiene copolymer. Vinylidene fluoride-hexafluoropropylene ca polymers (minimum number average mo- lecular weight 70;000 as determined by os- motic Pressure in methyl ethyliketone): Vinylidene fluoride-hexaf7uoropropylene-te- trafluoroethylene copolymers: (miidmum number average molecular areight' 100,000 21 C2~'R 177: 2600I 1157 ,049 1
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57,134 Food Additi5res 1122' 6-18-84 2.2" Methylenebis(6-tert-buty1-41 ethylphenol,). 2,2" Methylenebis(4 methyl', 6-tert-. , butyl- phenol ). 2,2` Methylenebis(4-methyl' 6-nonylphenol). 2,2'-Methylenebis(4-methyl'r6-tnrt- octyll phenol )'., Monooctyl- and dioctyldiphenylamine. 1W,1W"-Di-p=naplithyl-p-phenylenediamine. Phenyl-a-naphthylamine. Phenyl-S-naphthylamine. Phenyl-(3-naphthylamine-aeetone aromatic amine resin (average molecular weight 600; nitrogen content 5.3 percent). o, andlp-Phenylphenol. . Polybutylated (mixture) 4;4'-isopropylidene+ diphenol. Sodium, pentachlorophenate. Styrenated cresols produced l when 2 moles of styrene are made to react with 1 mole of a mixture of' phenol- and' o-: m-, and!p+ cresol's so that the final product,has a Brookfield viscosity at' 25' C' of 1400 to 1700,centipoises: Styrenated!phenol., 4.4'-Thiobis (6-terl-butdl-mcresoU: Toluene-2;4-diamine. 1W-o-Tolyl-N' -phenyRp-phenylenediamine. p(p-Tolyltufanilamide) diphenylamine. Tri(mixed mono- and dinonylplhenyl) phos; phite. Tri(nonylphenyl) phosphite-formaldehyde resins produced when L. mole off tri(nonylphenyl) phosphite is made to react with IL4 moles of formaldehyde or produced when, li mole of' nonyi'phenol is made to react with 0.36 mole of'fbrmalde, hyde and the reaction product,is'then fur- ther reacted with,0.33 mole of phosphorus trichloride. The finished resins have a minimum viscosity of.20.000 centipoises at 25" C., as determined by LV-series Brook, fieldl viscometer (or equivalent) using a B1oj 4 spindle at 12 r.pjm., and' have an or- ganic phosphorus content of' 4:05 to 4.15 percentl by weight. (ivJ Plasticizers (total not to e.rceed 30 percent by weight of rubber'prod- uct): n-Amyl n-decyl phthalate. Butylacetyl ricinoleate: n-BUty1 ester of' tall oil, fatty acids. Butyl', laurate. Butyl, oleate. Butyl stearate. Calcium;stearate., Castor oill Coumarone-indene resins. 2',2'-Dibenzamidodiphenyl disulfid'e. Dibenzyl, adipate. Dibutoxyethoxyethyl adipate. Dibutyl phthalate: Dibutyl, sebacate. Didecyl adipate. Didecyl phthalate. Diisodecyl adipate. Diisodecyl phthalate. Diisooctyl adipate. Diisooctyl sebacate., Dioctyll adipate. Dioctyl phthalate. Dioctyl sebacate. Dipentene resin. Diphenyl ketone:, Fatty acids. Fatty acids, hydrogenated. Isooctyt ester of tall oil fatty acids. Lanolin, a-Methylstyrene-vinyltoluene copolymer resins (molar ratio l a-methylstyrene to 3' vinyltoluene). Mineral oil: Montan wax: n-Octyl', n-decyl'adipate: n-Octyil n-decyliphthalate. Petrolatum. Petroleum hydrocarbon resin (eyelbpenta- diene type), hydrogenated. - Petroleum~ hydrocarbon, resin (produced by the homo- and copolymerizatibn of dienes and,olef'ins of'the aliphatic, alicyclic. and monobenzenold,arylalkene types from dis- tillates of cracked ipetroleum stocks):. Petroleum hydrocarbon resin (produced' by the catalytic polymerization and' subse- quent hydrogenation of styrene. vinylto- luene; and indene types from distillates of crackedipetroleum stocks). Petroleum oii, sulfonated. Phenol',formaldehyde resin. Pine tar., Polybutene. Polystyrene. . Propylene glycoli - n-Propyl ester of'tall oill fatty acids. Rapeseed oil vulcanized with rubber maker's sulfur. Rosins and, rosin derivatives identified In g 175.105(cX5) of this chapter. Soybean oii vulcanized with rubber maker's sulfur. Styrene-acrylonitrile copol'ymer. Terpene resins. Triethylene , glycol i dicaprate. Triethylene glycol!dicaprylate. Waxes„ petroleum.' Xylene (or toluene)' alkylated with, dicyclo. pentadiene: Zinc 2-benzatnidbthiophenate: (v) b'i;Ilers Aluminum hydroxide. Aluminum silicate. Asbestos fiber, chrysotile or crocidolite. Barium sulfate. Carbon black, (channell process or furnacee combustion prooess; total carbon black not to exceed 50 : percent': by weight of rubber productt furnace combustion black con- tsnt not to exceed 10: percent by weight of' rubber products intended for use in con- tact with milk or edible oils)L Cork:. Cotton (floc„fibers, fabric). Mica. Q 1984, Commerce Clkaring House, Inc. 1(57, 049 21 CFR' 177 . 2600 ( c
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57,136 Food'Additives cleansed prior to their f'irst' use in con- tact with food. (h) The provisiions of this section are noti applicable to rubber nursing-bottle nipples. (i) Acrylonitrile copolymers identi-, fied in this section shall comply with, the provisions of! $',180.22 of this chap- ter. [21 CFR 177.2600 as of'Apr. 1,, 1983; amendeda 49 F.R. 4072, Feb. 2, 1984; 49' F.R. 10087, Mar. 19, 1984. ], [1157,050.1] § 1'77:2710 Styrene-divinylbenzene resins. cross.linked. Styrene-divinylbenzene cross-l'inked eopolymer resins may be safely used as articles or components of articles in= tended for repeated use in producing:, manufacturing, packing, processing;, preparing, treating, packaging, trans- porting, or holding f'oodl in accordance with the following prescribed condir tions: (a) The resins are produced by t'he copolymerization of' styrene with di~ vinylbenzene. (b) 1 The resins meet the extractives limitatilons prescribed in: this para- graph: (1) The: resins toi be tested are: ground or cut into small particles thatt will pass through'a ZD:S: standard sieve. No., 3 and1 that will be held oni a U.S. standard sieve No: 20. (2) A 100-grarn sample of the resins, when extracted with, 100 milliliters of' ethyl acetate at reflux temperature for 1 hour, yields total extractives not to exceed 1 percent'by weight of: the resins. (c) In accordance withi good manu- facturing practilee; finished articlles containing the resins shaili be thor- oughly cleansed prior to ltheir f irst use inicontact with food. l.W oI~ s1dHIAinCes. . (i? Fiheraa . .. , ., . . CanOM .----..... _-..__............................ .._........ -.._...... Rayon............. .._._...____.._.........._..._..... _._....... .... ....... Poly-yMene terepHMalate comp" n aaaqosdwn wiah the . I pranmons WI 1 R7, f 63qe)(N00• .~~~ 0) ndiwami swsunces: ~ /+wnrwum alearate...- ......... :, _...................... ....-.. oene-0aultona aed4 dsnWen aaK r.2'-am - .--` ......._ _ . ._ . ~ ' .~~2-Fymnmg ~ 8aras. .. I $57,050.1 21 CF'R 177.2710 1122 6-18-84 [ 1f57', 0'5,1] § 177:2800: Textilks and textile fibera. Textiles andtextile fibers y may safely be used as articles or, compo- nents of articles intended for use in producing, manufact'uring, packing„ processing,, preparing, treating,, pack- aging, transporting, or holding food, subject' to the provisions of' this sec- tiion. (a) Tlie:textiles and textile fibers are prepared, from one or' more of the fibers identifiedl in paragraph (d)' of this section and from certain other ad- juvant substances required in the pro- duction of the textiles or textile fiberss or added' to impart desired'properties. (b) The quantity of any adjuvant substance employed in the production of textiles or textile fibers does not exceed the amount reasonably re- quired ta accomplish, the intended' physical~ or technical' effect or any litn-, itation further provided. • • (c) Any substance employed'in, the production of textiles or textile fibers that is the subject of a regulation i , Parts 174, 175, 176. 177„ 178 and § 179.45 of this chapter conforms withh any specification in such regulation. (d) SUbstances empl'oyed': in the pro- duction of or added to ~textil'es and tex- tile fibers may incl'udir CL) Substances generally reeognized' as safe in food., (2) Substances: to prior sanc- tion, or approval for use in textiles and textile fibers and', usedl in accordance with such sanction or approvall. - (3) ' Silbstances. generally recognized' as safe for use in cotton and cotton fabrics used in dry food packaging. (4)! Substances that by regulation in~ this part may safely be used in the produetion of or as acomponenta of'~ textiles or textile fibers and subject to provisions of'such regulation. (5) Substances identified in this paragraph (d)(5); subject to such limi- tations as are provi'dedf Limitations~. Fon use ordyy m me , manuWcpxe ~~ of ~ ilems tar repea/ed use: Foa use as colorant only.. Fon use as . Weserealwe .on1,. Q 1984, Cbnunerce Clkaring: House, Inc. ( (
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1111 4-2'-ft qe ln•_~. o - . List ar substances i Lmdat'ans ; 57,137 Butw-aceuyt nanolea4e._»_..........___...._.._......___.......___......-..I I Oimethylpoysibsana ~ ._........-.._.._..........._..._._..._.._._......... '. Ethylenedamnetetraaceaa .cid-sodMam sed.......... ........_....__..... a!Etfry!I64!ns>aaOlY,y1 morplnoMftittm »aMyl sulltla..__..._.__...._....... EtgenmL-_._....._ __.....-.~..._......~_....._»_.._I Fats-oils, fatty aciOs: anO.faKyakaAots denveA flompsta. . aDaalraAJ cottonseed. 11s11;.mUstardseed..Valmk peanut. raCle- seea.l naetiran, soybi.an.' sperm,m and taM'.aas.and.taeow.. Fats. , oitr tatty' acids, and/aty .Wofw/s Qescribed . in the preeadkgiWa te.cted.wAh.pr Or..man.0f'tMe.lOlYOwerp . sabataacas; n-Bayl' andisaEuAyT Olel/yMae pYyW I______._._._..._.._--..._-_ ................. Oiewunolimne' ............. t C 1Methyl atcahol _...~..___. IsoprapM' akalno(.. Me>eykne ylyool(2?m~2.1`P.nWKdioll:_..--___...._.--.. Flydragqn.._.._ ..._~.._..:.___ ...:............... Polyetlryknr ylycal .(molewla[ weiplnt 400-3.0010).. ................. POtassaan 1Yydloxide - _-_.__- f/raOYbne 9" SOdilaro hydrppdd. . .._.-_..._.-_ Sulhai¢. Formtlc/elrype___._ ~ .-.. ~ 2~(9-HePladecetMy-+-(2dt~)~Yt•2. n.oaxain.n0 eMyl sOlfate.. FIlxylene g/ycd~ (2•metliryl.F2..'-pertlanedroQ' Isaburyl akanat___-._ _.._..-__.._.._....__._ ,. haprapyl ataatml- KerOsens _-.-.._.._._.__............~ ._......».._...»__w _..___..i. Mineral ail .._..._._.__ ....._..___~ Monoo- and diisapropylated m-~ andpvasols .(isottrymat derlva- ~. tive). , . 7.(2H-napnttw[1'.2,dlHiaxal-2yA)-31MnyWbtamarin (CAS.Reg.i No. 3993-62-91~.havrg a metlag,pamt!ol'.250`ta 251...C '.. and a rruogen aotNent!d 10.7 to 1:1:2lperaeM: iv;peyl'. M,acetyl. N=6-MdroxyethylonedLanwie---...._......-...._.. Pebalatwn:._............ _........ _............. _._.......... _...._.....------....... Petrdeua sunorwte .........»..._..........~.~___»__._._...........---_~ Pne', oill....... ....... _....... _...... __................ ........... _ ..............---.......: PolyGaene. tiyotlogernteE;, aqnpljrinfg" with the ~ IdenbtyY. Pre- scnEed under 21 CFR 1'78:3740(b):ot tlrscNapter. . PodyethyteneM oxddae0 (a.r bbwn):......... .....................................--.... POtyHny/ aeetate......... ----_................. -......... ._............. _..._..... . PWywelyl' alcalnd 1 ................ -----................ -....... _.............................. Potassium saaR cf a snpmrdled sulfated castor ad ....................... Sqdium.bs(2.6dMnetftytlwptyN) suHosuaumte ~ ......»...---_..-..... Sodium tlaa:tyl sWlosucnnate ,.......... _........................... _........... SaidwMe dOtlecyl benzenesdlenate..._..................... ...... .............. Sodium ttuande.__......... _....... -.-----._....».... _.... __.,...... _ ................ ........._..... Sodnrm flydrosul6te....... ._............... ........... .................... Sodium taueyl:sultate:._ .......................... ...... ..._......-.._..._............_.I Sodum 2=mertaPtoUenxothhaiate .... _..... __ ........................ ...._. _: Sodium qentacnioeophenate .... ................................ ................ styrene-tietaCtene . cnpoMmer :...............................................-......1 , Sultatea.buityld isabutyt ana.propyl ateate_ ............... .................... T a Y 1 a w -. .................. . . ......... - - - .................. . _ ............... . . - . . _ ........... - - - . . . . . ~ TaUaw.' sullomateA.......... ._ ............... ----................ -------------- ........... Tpaniumdioxide............. ._..-_.....-..-._ ...................._.......................... Tnethanatamme .......... .................. -_ ............................ _......----.. 131tramarere bdbe.-------- ----- -------------- -------------- -------- ----------- ...---...._.... waxes, petroleum _--.._....................... ....... _ .............................. Z.oc tryarosatfae .___.... __............. _....... ...__-._ .......................... Fioad IDrug, CasmeYic']Law Reports ts--Repeated! Use' Artic:]les For use only as ahtGricsA in tbemanufactuare.o('POMeOryket® te'rePbtlwlate Gbas specified . n. PanagraPh i (d)(5)(i) i of tBits section at a NvM:rtot to exaeed0.03percent by,'wephl of the f/n.sMed; fibers. Fa.use.as peeservativeanly. For use an6yate Ierel nat.to eaued.0:15'.percent by.weqM ol'ttawst,ee abers; FarOse only as.an optical dnglYtener n pdyetbylene terephth- alate bbers'spe'a4e0 in Raragrapei Id)(5)() of thws'.seaaam at a(evel not to ~ eatxed0.035 ~ percent by weigfnr Of I 1Nebnishie0 fibers. Fauser aspreservative onM. 6o. Do. 21 CFR' 177. 2800' 1157,051
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c c 11'1'0 3-26-84 Direct Substances P:fffirn>ted GW G157,917.661 §'1'84:1666 Propylene glycol'., (a) Propylene glycol (C,FLa=: CAS' Reg: N'o: 57-55-6) is known as 1'.2-pro+ panediol. It does not occur in nature: Propylene glycol is manufaetured' byy treating propylene with chlorinated' water t'o4orm the chliorohydrin which is converted to the glycol by treatment wit'h sodium carbonate solution. It is also prepared by heating glyercoll with sodium hydroxide., (b) The ingredient meets the specifi- cations of the Food Chemicals Codex;. 3d EdL (1981), p. 255: whiich is incorpo- rated by reference. Copies may be ob- tained from the National Academy Press, 2101 Constitution Ave. NW., Washington, DC 204'181 It is also avail- able for inspection atl the Office of the Federall Register, 1100 L~ St. NW., Washingtom DC 20408. (c) The ingredient is used as an anti- caking agent as defined' in § I70.3(o)(1) of' this chapter;.antioxidant as defined in, §1170:3(o)(3)' of this chapter dough, strengthener as defined in § 170:3(o)(6) of this cliapter;,emulsifier. as definediin §',170.3(o)(8) of'this chap~ ter; flavor agent' as defined in f 170.3(o)(ii2) of'thischapter;~ formula.- tion aid as defined in § 170:3(o)(14') oi' this cnapter; humectant as' defined in § 170.3(o)(16) of this chapter; process+ i'ng aid as d'efined in § 170.3(o)(24) of' this chaptler;,solc•ent and'vehicle as de• fined in & 170.3(o)(27) of this chapter; stabilizer and! thickener as defined in § 170.3(o)(28) of this chapter; surface- active agent as definedi in. § 1'70:3(o)(29) ofi this chapter; and tex- turizer as defined ini § 170:3(o)(32) of! this chapter. (d)The ingredient is used in foods at levels not to exceed' current good1man- uf'acturing practice in,accordance with § 184:1(b)(1). Current good manufac- turing practice results in maximum levels, as served, of'5 percent for alco- holic beverages, as defined in §'170.3(n)(2) of' this~ chapt'er; 24 per- cent for confections and'frostings as defined in §' 170;3(n)(9) of this chapter; 2:5 percent for frozen dairy products as defined in § 170.3(n)(20) of' thiss chapter; 97, percent for seasonings and flavorings as defined in § 1i7U.3(n)(26) of this chapter; 5 percent'Eor nuts and': nut products as defined in §1'70.3(n)(32)' ofthis~ chapter; and 2A' percent for all other food categories. Food Drug Cosmetic Law Reports 57„869 (e)' Prior sanctiio'ns for this ingredi- ent different from the uses established' in this section do not exist or have been waived. [As added, 47 F.R. 2'7813!, June 25,, 1~982. ]I [1I157',917.7] § 184.1670 Propylparaben. (a) Propylparaben is the ehemical propxll p-hydroxybenzoate. It is pro- dueediby the n-propanol esterification of p-hydi•oxybenzoie acid in the pres- ence of' sulfuric acid, with subsequent distiillation, (b)''II'he ingredient meets the specifications of the "Food Chemical's Codex." 3d!Ed. (1981), p! 258; which iss incorporated iby reference. Copies may be obtained from the National Academy Press. 2101 Constitution Ave. NW:,. Washington, DC 20418, or may be examined at the ©ffice of the Federal Register, 1100 L 3t. NW., Washingt'on, DC 2040& (c)'I'he ingredient is used as an anti- microbial agent as definedf in § 170.3(o)(2) 'of this chaptler: (d) The ingredient is usediin food at levels not to exceed' good manufactur- ing practices. Current good manufac= turing practice results in a maximurn level of 0.1 percent in food. (e) Prior sanctions for this ingredi- ent different from the uses established in this regulation do r.oe exist or have been waived. [As amended, 47'F'.R. 11853', 1«fair. 19'„ 1982 ; 4'9 P. R',. 5608, Feb. 14',, 1984. ] [1157„917.761 §, 184.1676, Pyridoxine hydrochloride. (;a 1 l?yridaxine hydrochl'oride (CbHiiNp:1;,HC1, CAS Reg. No:,5&-5ti-U) is the chemi'cal 3-hydroxy-4,5- d ihydroxymethy-2-me thyloyridine hyd'rochloride that'.is preparediby chemical, synthesis. ~ (L) The ingredient meets the specifications of the Food Chemicals. Codex: 3d Ed. (1981)J p. 260; whichlis incorporated by reference. Copies are auailable from the National Acadeniy Press. 2101 Constitution Ave. NW.. Washington. DC 20418; or available for inspection at'the Office of the Federal 21 CFR 184'.1'676Q57,91;7'.76
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C IHEMIiCAL REGULATIONS 174 AND GUIDELINES SYSTEM (CRGS) D~IIALOG INFORMIATIONRETRIEVAL SERVICE FILE DESClRIIPTION. CHEMICAL REGULATIONS AND GUIDELIINES SYSTE4 ('CRGS) is an authoritative index to U.S. federal regulatory, material' relating to the control of chemicall substances, coverinq federal statutes,, promulgated regulations and availlable federal guidelines, standards, and support documents. CRGS' follows the regullatory cycle and includes an up-to-date reference to each document, including main documents and revisions published in the Federal Register. Each chemi'cal' cited in a regulatory document is indexed by name, CAS Registry Number, and a chemicall role tag. The latter gives information on the context in which the substances appear in the document. CRGS also provides links betweeni the statutes, the regulations .promulgated' under these statutes, and the support documents generatied' prior to the promulgation of a regullatilon. Eachidocument is described' in terms of publication date, tiitle,, abstract, index terms, and chemicall identifiers. Index terms are assigned from, the CRGS Thesaurus whiehi will be available online in the CRGS file. SUBJECT' COVERAGE All aspects of regulatory control' ofi chemicals are coveredl including:. • Disposal • Trade Restrictions • Manufacture • Transportation • Occupational Health • Use • Product R''egistration Fields covered' include: • Aeronautics r Agriculture r Consumer Products • Cosmetics • Energy • Environment Protection, SOUIRCES' • Food • Mining • Nuclear Technology • Petrochemicals • Pharmaceuticals • Transportation CRGS represents d'ata, obtained from offiiciial sources of regulatory material including the U.S. Code andl its supplements, Statutes at Large, Code of Federal Regulations, Federal Register, and other materiali obtiainedl directlyf'rom federall agencies., DIIALOG' FILE DATA Inclusive Dates: AI'I regulatory material' in effect' as of' !st' May 198!1 Update Frequency: Mbnthly (approximately 11„000 records per upd'ate), File Size: 3,000' records as of November 119811 O IRI II G I N CRGS' is sponsored' by the Interagency Regulatory Liaison, Group, of the ULS. Federal Government and is prepared;, under contract, by CRC Systems, Ilnc. (luestions concerningi file content should be di'rectedlto: CRC Systems, fnc. Telephone: CRGS' Customer Service 40201 Williamsburg Ct. 703/385-0440 (ext: 120) Fairfax, VA 22032'. No port of this database may be duplicated in, hard-copy or machine readable form without written authorization from the database supplier, exceept' that limited repraduct'ion,of printed,, hard-copy output of' up to twenty-five (25)',eopies is permitted for distribution within the subscriber organization only. DIALOG is a, Trad'emarkof DIALOG Informatiion Services, Inc. Reg. U:Sy Pat6 & Trademark Office. (November 19801 174- I i
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FILE 174 CHEM]CAL REGULATIONS A11rJD, GUIDEL1hliES SAMPLE RECORD DIALOG Accession Number ANg SF= ~ 16024'9 1!507-0rJUS --J Chemical Imports and' Exports; Notification of Export. ' CS=-+EP'A„ Office of'Pesticides and' Toxic Substances . /TI , ~ CT=+CITATION: 40 CFR 707 CS PD=yPUBG. DATE:, 801216 EFFECTIVE DATE: 810115' JURISDICTIONa US!~ ED= , UT=yDOC. TYPE: Regulation STATUS: Fiinali . JUr . SOURCE!OF INFORMATION: 80/12/16I,, 45:FR 82844-82851 (40 CFR'707)' ST=-+AUTHORITYI: TSCA OS= NO. OF'REVS: 0 NO. OF CHEMICALS: 4 ~1746-O1-6II.S.N 2,3„7,8-TCDD ~ 3. 1'746 01-6'I.S.S'Tetrachlorodibenzo-p-dioxin~ 4.0 332-21-4':,I.S'.NL Asbestos:. SYSTEM (G'RGSY DIALOG FILE 1'74 . - . 1336~36-3 I.S.SIPOlych lorinated' biphenyri!s RN=~~ Z. u I1.~S:. N CFC' s. CN=, /SB'. - s SEARCH OPTIONS RL= BASIC IIVDiEX I SUFFIX' FIELD NAME' EXAMPLES None Basic Index (Includes E EXPORT S COMPLIANCE Abstract, Descriptor, Regulated Substance, andlTitle) /AB' Abstractl S' REGULATORY(W)ACTION?7A8 /DE Descriptor l S ORGANIZATIONAL ENTITIES/DE /58' Regulated 5ubstance S CFC'S/SB /Tl Title j S CMEMICAL(W)1MPORT?/TI IAIso /DF. A@m!ITIiON'AL !IIND'EXES PREFIX FIELD NAME EXAMPLES AN= CRGS Accession Number E AN=1607' S AN=1507?, CN= Complete Name2 E CNI=PCB', S CN_ASBESTOS I CS- Pnamulgating Agency and Office, E CS=OFFICE S CS=EPA' CT= Citation E CT=40 CFRI S CT=40 CFR 707 DS= Document Status: E DS=IN EFFECT S DS=FINAL DT= Document Typr E DT=GUIDELINES S DT_REGULATION I EDt Effective Date: E ED-8001 S ED=810115 JU= Geographic Code E JU-USCA S JU=US PD= Publication Date E PD=8001 S PD~80I2I6. RL- Ro1e Tog E RL=1 SI RL-ISN RN= Registry Number E RN=1336I 51 RN=1,332-2I-4 SF= Subfile (Jurisdictian)' E SF=US 5 SF=US ST= Statutory Authority E ST=CAA S, ST=TSCA I 2/4/sa searchable in the Basic Index. LIMITING GG I The LIMIT conwnondlis not applicable in File 174. SOR'TIfiNG SORTABLE FIELDS Online f.SORT) and offline: (PRINT): CS,, CT, DT, ED,, JU,, ST., FORMAT OPTIONS EXAMPLES .SORT 5/J-69/CT PRINT 5/5/'I-69/ED/JUI DIALOG Accession Number Full Record except Abstract and' Chemical Terms Bibliographic Citation Tlitle,. Abstract„Eh.mico{17er...s I Direct record access is not applicable in File 174. Outlines procedures for exporters to submit notifications to TSCA (Toxic l Substances Control Act). Also outlines the procedures EPA will use in notifyi'ng I foreign governments of' such actions as required by TSCA. *Notifications are '/AB required whenever eertai'niregulatory actions have been taken under TSCA wi'th,l respect to a chemical substance or mixture. (45 FR 82844,, Dec. 16, 1980.) DESCRIPTORS: Legal,Actions And Procedures*COmpli~ance, Confidential InEormation,) Program Compliance Directives; Organizational Enti~ties-Agencies, Foreign,?',~~Of Records-Reporting; Trade-Exports, Imports 1 CHEMICAL TERMS: i- RL= 1 1336,36 3 I rS~'PCB'S' ,yJT cs _ AoT I f wtptiC~re.X ~ I 1I7'4-2 (November 1981)
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Fide 174:Chemical,F:egulations,and Guiidelines,Sy,stem - Nov'1982 SS 35 RN=57-55-6 OR'PROPI"LLENE(W)GLYCOL. Jan. 30, 1976. 17'/7J 1 632-0 US Tolerances and Exemptions from,Tolerances for Pesticide Chemicals in~or on Raw Agriclturali Commoditiies. EPA ; Office of Pestiicides and Toxic:Substances Ci,tation:, 40 CFR: 18n Publ. Dater 711125 Effective Date: 711125 Jurisdiction: US Doc. Type:REGULATION: Status: FINAL Source of' Informati'on: 8n/p7/rr1,,. 4U CFR 100 Authari'ty:: FIFRA No. of Revs:: 1481 No. of Chemi,cals: 1:0--2; INCOMPLETE DISPLAY!.. Regulations for tolerances and exemptions for residues of pesticide chemicals in or on raw agricultural: commodities, are defined and interpretedl„ procedures f'or fil'ing petitions and for other Iega:l, and administrative steps are put forth, specific tolerances for individual pesticide chemicals are presented, and the handling.ofl residue test data is directed. *Listings are given,of categories and groups ofl raw foods and feeds according to perishabi;lity, relati~ve timing for use of'ehemical, processing of the commodity„ and f'ate of the chemicals (including introdLtction to other stages in the food chain). Pesticide chemicals are classified into safe, deleterious, i'nert, and either having zero tolerances or being exempt from tolerances. The'regulation calls for permanent or temporary certifi,cation~ of' chemical usefirlness and estimate of' residue, for judicial r-eview, of petitions for exemptions, and for the,amending or repealling ofl specific tolerances or exemptions when reasonable grounds action are developed. Procedures and fee structures for peti~tions are det'ai,lledL Several tabl!es of chemical groupings are presented. (411 FR 4'.:,37„ 17/7/2 664rV WS Identification and List'ing of: Hazardous Waste. Juri,sdictionr. US Regulation' identifies and lists soliidlwastes suoject to regulation as hazardous wastes. *Subpart defines "sol'id,waste" and "hazardous waste", identifies certain exclusions, and gives special management requiirerents, for hazardous waste produced by small qutint.ity generators or which is used, reused, recycled, or reclaimed. Subpa:rt 8 describes criteria for identifying and listing.ha.zardous wastes. Subpart C giues characteristics of' hazardous was+_e. Subpv.rt D, lists apeci,f'ic hazardous wastes. Five appendices describe ru~presenL'ative sampling methods, toxicity test precedures, chemical analysis test methods, bases for listi,ng, and hazardous constituents. (45 FFa .'T119', May 19„1ri8O. EPA Citatiions 40 GFR 261 Publ. Dates. 800519 Effective Date: 001119 Doc. Type:iREGULATI',ON Status: FINAL Source of Inilormation-: 80/07/01, 40 CFF Authority:'. RCFA' No. of'F:evs:: 25, PJo, of Chemi ca]. s: 5.^_2.
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17Y3Y3 '064-1< Hazardbus Waste Management System: I~dentification and Listingl of Hazardous Waste. EPA ; Office of' Solid Waste Citation: 45 FR 78532 Publi.Date: 841125' Effective Date: 801119 9 Jurisdi,ction:'. US Doc. Type:RESJISION REG Status: FIiNAL Authority: RCRA' No, of Revss, 0 No. of' Chemiicals: 82 117/3/4 783-0 Poultry Products Inspection Regulations. USDA ;, Food safety and Qual i ty Service Citation: 9 CFR 381 Publ. Date: 720516 Effective Datet 720516 Jurisdiction: US Doc. Type::REGULATI'ON StaYusv FINAL Authority: Poultry Products I'nspecti,on Act No. of Revs: q' No. of Chemical's:: 108 117/3/5 965-0 Hazardous, Materials Tables and Hazardous Materials Communications Regul'ations. DOT ; Office of'Hazardous Materials Regulation Ci;tation:, 49' CFR 172 Publ. Datem 760415 Effective Date: 760415 Jurisdiction: US Doc. Type:REGULATLON Status: FINAL Authoriity!:, HM'TA No. of' Revs: 1., No, of Chemicals: 18Cic?;, INCOMPLETE DISPLAY. 1,7/3L6. 102C1'-Q Criteria for a Recommended Standard'....Occupational Exposure During the Manufacture and Formulation of Pesticiides. NI',OSH Citation:: NIOSH!78-174 F'ubl,. Dateu 7e0701 Effective Date: 780701 Jurisdiction: US~ Doc. Type:GUIDELINE Status: RECOMMEND Au.thori'ty: Misc. Administrative Authorit,y No. of Revs:: 0 No. of Chemicalsa 128' 17/3/7 1068-0 Criteria for a Recemmendedl Qt'andard....Occupational Ei:pos»re to . 1,1,2,2-Tetre.chlloroethane. W N6IOSH'. ; H6 -a Cita.tion: NIOSH 77-121 bDy Publ. Date: 7612011 Effeetive Da:te: 761201! Jurisd'action: l-S, w Doc. Type:C,tUIDELINE Status: RECOMMEND IPA Aukhor ilty: OuHACT' ~ ~ No. of Revs:: 0 , No. ofl Chemicalsc 29 ~
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17/ 3/8 11141-CI: TLVs, Threshold Li'mit Values for Chemical Substances,in Workroom Air: . Adbpted by ACGIH for 19E30. Citation: ACGIH 11980 Fubl. Date: BC+ir,lf_r1, Effective Date: 000000 Jurisdi,ctione US' Doc. Type:GU'IDELIINE Status: RECOMMEND No~ of Revs: 0 No6 of' Chemicals: 681; INCOMPLETE DISPLAY. 117/3/9 1485r0 Unmanned Baroes Carrying DOT ;~ U.S., Coast Guard Citation: 46 CFR 151 7oCl225* Juu-isdiction:~ US Authority: Misc. Administrative Authority No, of Revs: 4 No. of' Chemicals: 409 Certain Bulk Dangerous Cargoes. Effective Date: Doc. Type:REGULATIION Status: FINAL Publl., Date: 7UCILLJ* 17/3/10 1488-9 1 Special Ihterimi Regulations for Issuance of', Letters of Compliance to; Barges and Exi'~sting Liquefied Gas Vessels. DOT ; U.S. Coast Guardl Citationv 46 CFR' 1,.°,42I F`ubI. Date:; 730615* Effective Date: 7'Crb1:,+r Jurisdiction: US Doc. Type::REGULATION Statust FINAL Authority: Misc. Administrative Authority No. of Revs: 0 No., of Chemicals, 218'.
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FILE DESCRIPTION T!he FEDERAL RESEARCH IN PROGRESS (FEDRIP) database provides access to inforrmation about ongoing, federai,ly-funded': research projects in the fields of' physical sciences, engineering, and life seiences:, Project', descriptions generaldy include: project title, keywords, startl' date,: estimated completion d'ate, principal investigotor,, performing! andl sponsoring organizations, summary, and progress report. Record content varies depending on the source agency. The FEDRIP database iis produced' by tihe. Nationali Technical Infiarmatiion Serviice (NTIS) and', continues, in part, the database functions of the now defunct SmiithsonianiSaientific Information Exchange (SgIE).. FEDRIP' provides a unique nonbibliographic information resource of research, in progress., Thus, it can be usedl to avoid research duplicatiionj Ilocate sources of' support,, identify: I'eads in the liit'erature, stimulate ideas for planning, identify, gaps in areas of' investigatian, locate individuals with expertise, andt cornplement bibliographic data. _ SUBJECT COVERAGE i FEDERALL RESEARCH IN PROGRESS covers physical sciences, life sciences, andl engineering, and inclludes but ist not limited to, the folllowing: • Agrievlture. • Instrumentation •Earth Sciences•Mied"acine• Electronics • Occupational Safety and Health • Engineering • Transpbrtatilon SOURCES Research summaries are eontributecil by the following U.S. federal agencies. (Other agencies may be added in the future.)' • Department of Agriculture • National Institutes of Health. • Nationall Aeronautics and Space Administration (NASA) • Transportatiion Research Board' • Nationall Bureau of' Standards • U.S., Geological Survey • Notionat Irutitute for Occupational Safety and Health, • Veterans Adfninistration. DIALOG FILE DATA Irnclusive Dates: Current research Updhte. Frequency:! Semiannual! ('relbad)'. File Size:~ 711,704 research summaries as of November 11983 ORIG IN FEDERAL RESEARCH IN PROGRESS is compiled and distributed' by the National • Teehnical Information Service (NTIS). Questions concerning file content should be directed to: Alan R. Wenberg, Telephone: 703/487-4807' Product hilarwager Telex: 646117 ~ FEDERAL RESEARCH IN PR.OGRESS ~ NTi IS ~. 5;285 Port Royal Road ~ Springfield VA: 22161 ~ , ~ f LC No speciat'. termis or eonditiians. W DIALOG is a Serwiicemark of DIALOG Informatiion, Services, Inc. Reg. U:S. Pot. & Trademark O'ffice.. CDIALOG Information Services, Inc., 11983:, AII'rights reservedl (November 11983)' 2654
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~_oP Z(__;, S6 112 PfiOPYLENE ( W)GLYCOL^ 6/7/1 01072181 IiDENTIFYING NO.: S,F'1OICA381,31'r01 AGENCY CODE: HHSNI Glyceryl monooleate' and pancreatic carci'mogenesis (rats), PRI'NC'SPAL INVESTIGATOR: LONGNECt,EE., DANIEL S DARTMOUTH MEDICAL SCHOOL DEPT OF PATHOLOGY, HANOVER:, N H 03756 F'ERFORMI'NG' ORG.: DARTMOUTH COLLEGE, HANOVER, NEW HAMF'SHIiRE SPONSGF(ING'ORG.:NATIONAL CANCER INSTITUTE FY : 84 Glyceryl monool'eate and pancreatic carcinogenesis (rats), 6/7/9 0066677 ' IDENTIiFYING NO. e 0045547; 6'435-20543-00SD AGENCY CODE: AGR' DETERMINATIiONI OF RELATIONSHQP OF STEREOSPECIFIC TRIGLYCERIDES OF'PEANUT OIL TO ATHEROGENICITiY PRINCIPAL INVESTIGATOF:: WHITE F L SR ASSOCIATE INVESTIGATORS: PARRISH F W;, BAILEY A'V PERFORMING ORG.: SOUTHERN REGIONAL RES CENTER, SOUTHERN REGIONAL RES' CENTER, NEW ORLEANS, LOUISI'ANA70:179SPONSORING ORG.:U. S. DEPARTMENT OF AGRICULTURE,AGRICULTURAL RESEARCH SEF:Vd CE 790813 TO Fd40B13 OBJECTIVE: Synthesize certain stereospecific triglycerides of dual-labeled', fatty acids and relate glyceride structure to the hi'gh atherogenici~ty of' peanut oil., APPROACH: Develop procedl.rres for synthesizing sizable amounts of stereospecif'ic triglycerides identical with both those believed to cause the relatively marked atherogenicity of peanut o-al' and those believed to be, innocuous. Develop procedures suitable for the preparation of sizable quantities of' odeic,, linoleic, and behenic acids, each labeled at two. Ievelis with a stable iostope (carbonrl's or deuterium) and prepare each of the labeled fatty acids in pure form. Synthesi'.ze selected stereospeiflicc trigll,vicerides of the dual-labeled fatty aciids, use these in short-term feeding tests with animals, andl establlish the reliat'i,ve proportions of thelabeled fatty aci'ds among the lipid' components, of'the circulatory system.. F'ROGRESS:: Work has corrtinued' on the preparation of the many intermediatee compounds necessary for the synthesis of peanut oil-type stereospeciflic' triglycerides containing dual-labeled oleic,,linolei,c„ and behenic acids, and exploratory runs have been carried out on the procedures to be,used ini preparingi the triglycerides. Sat.ch, quanti,ties of' the diketo acids of oleicc and erucic acid were prepared, deuterated, and reduced to the dlihydroxy acids for !rse in, preparing olei1c ..ci~d-[i,8',,11i,,11-d4, behenic acid-1^I,1'?,15,1i5-d4, and behenic acid4-12,12, 1I:',14,T5,15-d6. BQhenic acid-13,14-d(2) was: prepared by deuteration of erucic acid, aldl used ini thepreparatilon of ' tneh'anoyl-1'„14'-dl(2) -sn-g):yaeraL, a starti.nq mz.trerilal, +or some af' the triglyceride syntheses. F'ropylcene aly.coi monoben: oate wass prepared and reacted with triphrenylpho'sphi.ine in~1~ pre=ence of Hl+r r-ogiive the tr-iphc~nyla phospt-ionii.r.m ;tiali.de salt, which is an inter-medi,ate inthe prepar-ation of l:abelled lineleie aciid via Wittig, coupli,ng with deuterated' he:;anai and a-_aaldehyde. 87491294 10 >
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V DIALOG ® INFORMATION RETRIEVAL SERVICE 161 OCCUPATIONAL SAFETY AND HEALTH CNIOSHa FILE DESCRIPTi IION OCCUPATIONAL SAFETiY' AND HEALTH (NIOSH) is the bibliographic database prod'ucedl by the Nationalllnstitute for Occupational Safety and Health. Artlicles entered into the database ore token from several sources dating bock to 1973, as well as important articles from the early literature, some dating bock to the nineteenth century. Coverage includes a) over 1150' current journals in health and safety ond related' fields, b) alf NIOSH publications, c) pre-1974 abstracts from ILO/CISy, and d) odditional pertinent references generated in the creation of NIOSH documents. A111 records contai'n' abstract's and are also indexed with the NIOSH controllled'vocabulary. SUBJECT COW'ERAG'E' OCCUPA'TIONAL SAFETY' AND HEALTH (NIOSH) covers virtually all aspects of the occupationall safety and' health field. Documents selected for the database must pertain to one or more of the broad areas of interest below: • Behavioral Sciences r Health Physics • Biochemistry • Histology • Chemistry r Metabolism • Control Technology • Occupational Medicine • Education r Pathology s Engineering • Physiology • Epidemiology • Safety • Ergonomics • Safety and Health Programs • Hazardous Wastes • Toxicology ' SOURCES The ongoing sources for the database are about 1159' core Engliish fanguage' technicali journals whichh provide the majority of records. Supplementing these are abstracts of all NIOSH publications and' selected articles from journals of' special importance to the occupational health and safety field:. DIIALOG' FILE DATA Incfusive Dates: 1973 to the present Update Frequency: 'Quarterly (approximateNy 3y,000'records per update) File Size: 106,373 records as of December ['1984 ORIGIN OCCUPATIONAL SAFETY' AND HEALTH (NIOSH) is produced by the National Institute for Occupational Safety and' Health. •-QUestions concerning file content should be directed to: Mr. Ted Schoenborn Telephone: 51'3/684-8326. Technical I'nforrnation Branch National' Institute for Occupational Safety And Health 4676 Columbia Parkway Cincinnati, OH 45226 ~ Neither the United l Stat,es Government, nor ary ogeney thereof, nor any of their contractors„ subcontractors or, employees makes any, warranty, expressed or impliied.including any warranty of' merchantibility or fitness for' a particular purpose; nor assumes any, legal liability or' responsibility for' any party's use, or the results of such use, of' the Data Base. CC ~ ~'. C)UTA'ILUQ, Information Services, Inc., 1985. All rights reserved. (January 11985) 1 61-1
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~ `-VA*_A^1' ~ 1" r.Pi ~iv, ~ ' t-M~f\~ 0109198 NIOSh{-0013~68 9~689 ll' ~.. ..,., .. Spt~fum :Y` Cy~'ol,ogy'xAf ter. .I n'h~l at i on :;of ,'_IHe~ted' iP.rop~1 ene.,G1.~iQO1 r.' A Lr'1linicalCorrelation ~ Olsen, C'. R., W., F. Froeb, and L. A. Palmer i' Journal of the Amet-i can Med'i cal Assoc i at i on, Vol. 178', No., '6„ pages254-^56, 15-references Novermber 11, 1961 CODEN: JAMAAF^ . Inhalation of heated propylene-glycol (57556) CF`G>' as a tool for sputu!mcytology was tested. Since some patients are unable tn-raise spurtum4 a clinical trial was ruun on the inhalation of heated PG. There were three groups of patients: patients with suspected d'i agnosi s of cancer, pati ents wi th a hi story of heavy smoF:ing, and patients with undiagnosed pulmonary disease. Many suffered from chronic bronchitis or emphysema. Seventy nine percent of the pati ents were f rom 40-to 69 years of age. Heated PG was inhaledl for 20 minutes. After inhalation, sputum was collected in alcohol and smears were prepared. Cell blocks wer-e pr-epa:red wi th the remai nder of the sampl e. F'ati ent acceptance of the mst.hod~ was good and the warm"vapor was soothi ng f or- many. F'at i ents pre•.<i ousl y unab l e to rai se sputum were ableto give adequate samples after inhalation of PG. Inn those who were ab1 e to rai se sputum wi'thout F'G, thei r samples were i mproved i n"qual i ty af ter i nhal at iion of' F'u because of a decrease in nasopharyngeal secretions. Sputumicytology provided the first definite proof of pulmonary malignancy in eight patients. Identification of tumor type was not always possible. In some cancer pa.ti ents, cel l b1' ock:s showedl mal i gnant cel 1 s but smears di d not. The authors concl urd'e that i nhalat i on of heated' FG is a. useful tooll for sputum cytology. .
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., J 19I7F30106026 I!`1 I OSH=-001^ 98 z0 i~roducti on of Rat Sarcoma. Sol'ution,~of p--OUinone Umeda, M. days,, and increased to c:?.4'gd'1 .. after 173 days. Of the 24 rats r-ecei vi ng ON, 17 survi ved the test per i od of 334 days, having received 32 injections for a tota:l of 81 milligrams QN'' and 16.5cc PG. Fibrosarcomas developed in two rats. A tumor was palpated in one rat at 394 days andl the animal died at 423 days. 4,tumor was found in a second animal at 417 days and the rat was sacrificed in a weakened condition at 481 days. A . jrU VJU~~(,V Fry Inj'ections of Propylene Glycol G'ann„ Vol. 4'8+cNo. 2, pages1:;9'-1:44Yplat:e, IZ referencesJun:e-1957 The carcinogenic effects of 1,4I-benaoquinone (106514) (ON) and propylene-glycol (57056? P6) were examined in rats. Subcutaneous injections of. ON dissolved in PG at the concentra ti on of 1- gr-am deci l i ter .(gdl) were given week.L y to .1'5 Wistar- rats and' 9' hybn*id rats in 0.5 cubic centimeter (cc) amounts. Injections wet e_del!ivered into the same site on the back of the rats. Concentrations of' ON were reduced to 0.?gdll after 53 ma.croscop i c metastasi s was f ound' i n the 1 ef t a:xi 1 l a:ry 1 ymph node of the second rat. A cysticercus sarcoma of the liver was found in a third rat that died at 566 days. The two fibrosarcomass were found'in subcutaneous tissue at the injection sites. Ini-a second experiment, 18 r ats received weekly injections of icc PG for 8'8 week;s. After 15 months, the amount of PG was reducedl to 0.5cc., Eleven rats survived 300 days or more. One survived' 614 days. No tumors were found at the site of injection in rats recei'vi ng PG. The l oc~.~l t i ssu!e at the PG i n jecti on si tes showed hyal ine f ibr-osis. One of the r~, ests died at 4Wdays. At autopsy, and adenoma of the hypophysis was found. The author concludes that F'G may facilitate the penetration of' ON into the cells. U~ W_ P'40 JI - -1°JC a 41
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1'9i7'/7 c_ri )9147C N I OCE Ir-0C1 120 102 Contact Allergy From Propylene Glycol Ange1 ini ,['. , and C. L. Meneghi ni Contact Dermati t i s, Vc,].I., 7, No. 4, page rc f er-pnces 1901 CODEN: CODE:I}c F';ller-gic reactions to propylene-glycol (57556) 197-190, 8 were studied in 400 sub jects with eczematous contact d~ermatitis. A' 2<r per- cent propylene-glycol solution was appl.'ied tn th,e sub jlects by patch tests. F'o,ii~=ive reactions to propylene-glycol were recorded in six individuals. A'dverse r Fac:tions were confined' to the face, rb j ects hands,, or f or-ea.rms. The authors note that al'' 1 si :: of the ss wi th a posi ti ue response had a hi stor-y of prol onged contact wi th propylene-glycol through pharmaceutical and cosmetic preparations. (It 19/7/9 0082044 NIOGH-001 1090b Ftesults WFeeding4FropyTene Glycol in the_tDiet tor. Dogs for Two 1Gears Wei 1, C. G. , M. D. Woodside, H. F. Smyth, and C. F". Carpenter Food and Cosmetics Toxicology, Vol. 9" No. 4„ pages 4I79-490,, 14 references 1971 CODFN:. FCTXAV The ef f ects of l ong term f eed i ng of propyl ene-g l ycol (57556) were stutdi ed i n dogs., E;eagl e-dogs were fed 2.0 or O. U grams per kilogram (g/E;;g) propylene-glycol for 2' years. An i mal s were weighed weel'~1 y, and hematol ogi cal , urol ogi caL , and histological a:nalyses were performed. Mean body weights of propylene-glycol tr eated dog,wwere comparable to those of controls throughout the experi'.ment. There were no significant differences between~ treatment and control groups in mortality,; water con sumption, or diet utiliaation. At the 2g/k:g propylene-glyc+vll d'ose, there were no differences in hem~.~tological, histological, or urologicall parameters in, the experimental animals. In the high dose group, the rate of er ythrocytic hemol'ysi s ilncreased, but this effect was reversible a.nd'not permanently damaging to the spleeuor bone marrow. In males fed 2g/k:g/'day, there was a significant reduction in li.pidl formation rate in tl'ne liver compared t6 control.'s. The-aut:horsconcl u!de that 1 ongl term feeding of propyl'ene-glycol in, amounts as high-as Ci~percent per day does not have adverse ef f ects i n dags..
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f ~ ~ S ~ lrz ~~ u v ui ~ 19/7/17 0i a,-~4Ci21 N I OGH-Cr0t:a4i ti GO a~ a V-L^ " . t '1 r `L~~,,~ j ~ Comparat i ve Ef f'ects of F'ro l ene py Alcohol on the Liver Directly Gl ycol , Other 61 ycol s, Newman+ H'. W. , W'. Van Winkle, Jr., N. K. k:ennedy, and M'. C. Jourrnal of F'harmacology and Experimental Therapeutics, Vol. 68'„ No. 1, pages 194-2ircj, 13 references January 1940 Comparative effects of propylene glycol, other glycols,, a:nd' al cohol on cat l i vers were i nvesti gated i n e::peri mentali studies. F'ropyl ene gl ycol decreased the oxygen consu.mpti on andd carbon dli oxi d'e pn-odurcti on of perf u!sed i sol ated cat 1 i ver , but i ncreased glycogen of the l i ver and l act i c ac i 6content of' the gl ycol liver, utilization of glycol. Ethylene glycol, dliethyl'ene~ glyc'o3'',andl di propyl'ene gl ycol were not u!ti 1 izedi by` perflusedl l i'ver, but depressed' oxygen consumption and increased lactic acid production, dipr op:ylene glycol being least toxic in these respects. Ethyll al cohol was metab o1 i. zed di r-e=t 1 y by per•-f used liver, but depressed its functional activity; blood lactic acid was irnc:_reased' and liver g.lycogzn decret.sed. The direct azcti on o-f propylene gl ycol on i. sol ated T i ver stands apart f r orri the zcti ons of ethyl zl cohc_i1 and other gil; ycol s; propyl ene glycol is the least i'njur-io!rs and objectionable oT all these solvents.. blood and decreased urtil'iza.tion of dextrose by the liver. Addition of insulin to the perfusion with propylene caused itu-ther- depression of oxygen consumption of the prevented increase o-fl blood lactic acid, and' hastened 19lZ/ 1 6. 003:7737 I"d liO-SH-00ij4!:',i64 Compa.rative Effects of F`ropy,l'ene Glycol' a:nd Some Other Agents on Oxygen Cons_impt i on of the Organi sm V a n ttJ i nE:: le, W.,. J r- ., J'oarrnal of Laboratory y and Cl.'inica,l tlediciine, Vul. :`7,. No. 6, pages 770-773, 2 references March 1942 The metabol i c acti ons o-f propyl ene gl ycol , r-rsi ng consumption a.s the criterion, have been studied. Propylene was found to depress the o:cygen consumption of white this depression not being due to~ a ox Y9err glycoll rats, decrease in activity, since the depressions of pentobarbital ch1'oral i rr the same rats di d' noi_ si gni f i cantl y decrease oxygen consurripti on. These resuul ts on whol e ar-,i m<<l __. with previous results on isol:a:ted' liver perfused glycol, whi'ch al=s.,o showed' a decrease in oxygen The doses of' propylene glycol used were•e be taken as solvent or vehicle in food or- arrd Mort on~ andd the are i n agreement with propylene consurmpt i orr. beyond those l i k:eliy to medicin4.1 agents, but thee depression of o: ygen consump.tionicow.ld occur large or toxic doses. This result is essentially of i mportctnce, because the use of propyl ene gl ycol has a of sa:f'ety, with very scientific wide margin
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i. S' / , ; .• r'; f j(-) 2 rf:: 7 2, IN 10 S f,I-i=)(j(=) .=:192 '1 Hematolocri c Effects fcrl lowingi the Imtra,venous Injection of Propylene Glycol in the Rabbit Lri. ttain, (";. T., and F'. F. D• Arcy. To=; i cc;loc!•; ,:nd Appl ied' F'frarmaco7 ogv, Vol. 4, No. 6, pages 738-744, Sreferences Noverrrrbeir 1R62 ' F-Iematoloc!ic ef+ects foll'owing intravenous inj'ection of propylene glycol in rabbits were e:;per-imentally studied'.. The a:dmini.str-ation~ of concentrations o,fi propylene gllycol (4 m3'ik:g) in saline (1:`....,, 25, and 50 percent) to rabbits ha.d noo effect on red blood cell courrt, pa.cE'::edl cell volume, hemoglobini concentrati'on, or total white blood celil count. There was, horye ver , an i ncrease i n the number of ci rcul ati ng poI ymorphs, and ee decr-ea:se in, the lymphocytes. Monocyte, eosinophil'e„ and basophile counts were not affected. Blood clotting time markedly decreased and there was an accompanying increase in platelet count. The fragility of the red blood cel:ls was not altered. 19:!7/211 0025332 N I DSH-t=)0062574' Observati.lonson~ theEhronicTo,ricitiesof P'ropyleneG'lycol, Ethylene Glycol, Diethylene Glycol, Ethylene Glycol C1ono-ethyl- %etFr,er-•, aWDiethylene Glycol Mono-ethyl-•ether Morris, HI. Ji., A. A. Nelson, and H'. 0. Calvery Journal' of Pharmacology and! E:cperimentall Therapeutics, Vol. 74, pages 266-273, 21 references March 15+42The resul ts of' chr-on,i c to,y i city studi es of propyl ene g1' yeoS , ethylene glycol, diethylene glycol, ethylene glycol monoethyl ether, and diethyl ene gil ycol moneethyl ether on e::peri mental' rats are presented. The results obtained by continuing the experiments for two years that would not hnve beerr noted i.:f it had been dli sconti nta.edl at the end of one year were the occurrence ef ur°inar y calcul i i n each om the ser i es of the animal s receiving ethylene glycol and diethylene glycol. It is possible alsr that the microscopic-l'esions and testicullar enlargement observed wRruld' not have been as d'istinctl y diff'er-ent between the e;:per-i mental and control ani mal s if the e•:, per iment had been contirrued for only one year. Fully two-thirds of the animals on ethylene glycol monoethyl'l ether showed marked testicular Enlargement, edema and tubular atrophy. This condition occurrred less frequently in the group of diethylene glycol monoethy] ether and only occasionally lotheother experimental groups and in the control groups. Chronic kidney damage was mar ked' and renal corrncretions of calcium oxalate frequent only in the case of'~ those animals receiving ethylene glycol. ?ihe gr-oup of anima.l s receiving propylene glycol di'ffered only very slightly from the contr-olls.
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15"i ' /2'2Cr(:)27,9E;:' h1I QSH-00<<r3.-027 F'ropyl ene G'1 ycol : A F'otent i al l y To;c i c Vehi c le i n Li qui d Dosage. ol"m Martin, [". , and'L. Finberg Journal of F'edi.,_,rt.ric=_•, Vol . 77'9 No. S, pages E7%-B7E, 8 rE•ferences Nwermbt:.r.. 1970 A case report i s presented f or a_n~~~- morrth-oI d p.at i ent exhibiting toxic symptomatology while-recei.L<ing large doses of vi tami rr C suspended i n propyl en€+ g I yco1. , common 1 y enip loyed i n pr-F•p.?:ring oral and in i'ectable me ica:tions sti_rch as bf.rbitu.ra.tes, antihistarnirie.s, and vit.amins. The form of i.ntoxicatior, fi-ome the glycol is similar to thF type resulting from an overdose of ethanol, with irregular apical heart rate and sinus arrhythmia: being observed in--the present case. The occui~~rence of symptoms in the patient suggests that propylene glycol may be toxic when unusual doses are administered, especially to children. 19/7/24 0022950 haIOSH--00062541 Studies of Skin"Reactions to Propylene Glycol Warshaw, T. G.,„ and F. H'errmann Journal of Investigative Dermatology (F"aper preseritedlat 13th Annual Meeting of the Society for Investigative Dei~~-matologiy, Inc., June E, 1952), L'crl. 19, pages 42:-•4?0, 20 references December 1. Clinical studies of skin reactions to propylene glycol have been reported in, which undiluted propylene glycol produced positive patch test reactions in 138 Cnearly 16 percent) of 866 . subjects attending the clinic because of various allergic or- possibly allergic dlermatoses. Although it was not possible • to dec i!de whether the pos,i: t i ve reacti ons were due to speci f ic sensitizaiton,, it appeared more likely thatt they were caused by primary irritation, It is suggested that excessive dehydration of skin may be an important factor pr-edi=.posing, to the reac:tiorrs.. In conformity with th~is assumpti'on, the incidence of inflammatory responses was at its minimum during tthe hot and humid sea.son, and' high during, period's of low environmental': temperature and humidf.;ty, when there isy norrna:lly agreater tendency to dehydration of the skin's surface tissues. Similarly, a distinct reduction in the intensity of the patch test response was observed in 2 oi 3 subjects tested after stimulation of sweating by e.;posur-e to heat. (Discussions withI:)r. Warshaw's replies appear following the articlie. )
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1 e!',!? /? 5 iat:i ,`'554 N3.t1SH~.~-()t)i;6 jA 5): The Genera]i Er ope>rties, Gl. ycol (lcti'orrs, and To>ri!c.i t.y ri-S F'ropyl!en'e. Seider+fel.d" Mi. A. , and F'. J. Harrzl ilk •Journa:l of f ha.rrr,a.col cgya.nd, E. ei 44', paC.ies 109--121 ,6 ref er ences Q ~ -irrental Thei-apeUtics, Go.l. The general pr oper-ties, irritant and toxic actions of propylene gllycol are discussed and compa.redl rsith ethylene g,]:yco]'l from thee standpoint of its, usefuln,ess„ and its substitution forr ethylene gl•.<cc;l, as a~vetii.cle and solvent Tc;,.r pha.rmaceutica:ll preparations in medicine. In e.:perimental andl clinical.l studies, propylene glycol caused a moderate, thougJh, fl:eeting, local irritation of mucosae, and i n t:.he musc l es and ss rbcutaneoua, t i saues of rats, rabbits and_~en, the irritation more,ma:rk:edl tharr that of ethylene glycol and glycerol., Thi.s, action is d'Ue to hyper- tonieity. In rats aWrabbits, the symptoms of' toxicity wer-ee characterii4e•d by general motor depression„ increa:sed respiratory rate, followed by tremors,,, coma and death after the 1argest doses. The continued drinking of 1, 2, 5, and 10~ percent sc1lc+.tionss in water of propylene glycol by rats during about one-eighth of the normal span of life caused n,o demonstrable effects on growth aWbody weight. F'r-act.ically no, pathological chang,es in~ the viscera examined were demonstreted!. As a, solvent and vehiclle, propylene gliycol of'fers generally all the advantages of ethylene glycol, and at the sa:rrre time, it is much:lt-,ss toxic and caerses no demonstrable ca'•:!mul ati ve ef f ects, at l east i n animals. it remains scal e i f' the apparent l y tol-be demonstrated on a much l arcrer somewhat greater local irritation,of th.e propylene glycoL might outweigh systemic to•:ici'ty iin its, general mEd ic irie and p:harmacy. the apparent advantages of low usee as a vehicle and solvent in
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1`-e/7/,'7 0021,!5:1': ly ll[.1aiH;-0t_?Cr61=7 j: If, Test s f or the Chron i c To:; i c i ty of F`ropyL ene Gl ycol and Triethyl'ene Glycol on Monkeys and Rats by V~por on and ~C1r-a1. Administrat.ion R oLier'tson, O. H. , C. G. Loo sli , T. T., F'LrcF:, }.I. Wise, }I. M. Lemon, a.ndl W. Lester, Jr-. Jour nal of' Pharmacology and Experimental Therapeutics, Vbl.. 91, pages 52-76, 27 references SeFtember 1947 Wi th a vi ew to deter-mi ni ng the safety of employi ng, the vapors of propylene glycol a.nd triethylene glycol in~ atmns- pher-es inhabited by human beings, experimental monkeys and ra.ts were exposed conti'nlcous7.y to high concentrations of these vapors for periods of 12 to 18 months. Equal numbers of control animals were maintained under physically similar conditions. Long term tests o-f the effects on ingesting triethylene glycol were also carried out. The doses administered represented ,..,0~to 700 ti mes the amount of gl ycol the arni mal could absorb by breathing air saturated with the glycol. Com- parative observations on the growth, rates, blood counts,, urine examinations, kidney function tests, fertility and general condlitions of the test and control groups, exhibited no essential differences between~ ttrem wi th the exception that the rats in the glycol. atrrrospheres e;<hibited consistently higher wei: g,ht gains. Some drying of the skin of the monkeys' faces occurredl after several months continuous exposure to a he&:vy fog of tre iethylene glycol.&Icrwever, when the vapor concentration was maintained just below saturation by means of the glycostat this effect did not occur. Examination at autopsyy iiF:ewise fail'ed to reveal any di.fferences between the animals kept i n g1l ycol ized ai r and those T i vi ng i n the ordinary roomm atmosphere. Ex tensi ;,*e hi st ol ogi cal study of the l ung s wa=s made to ascertain whether tFre g,l: ycoll had produced any genera:l i zed or local irritation. None was found. The E:iidneys, liver, spJ.eerr and bone marrow al Co were normal. The resu1 ts of these experiments in conjunction wit4the absence of' any observed ill effects in patients e,•:pnsed to both triethylene glycoll and propyl!ene glycol vapors for months at a time, prrovide assura:rrce that air containing these vapors irn"e:mounts up to the saturation point is completely harmless.
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1 r.:'' 7/ 2F. rjG?2,1= 1 =: N I C:1:;H-(i006Cr7E0.Tlo:;i_cityofFr`ropyleneGlycol! Wea:therby, J. HI., and H. D. Haag Journal of the American F'tiarrrEace•u_ical. Associa.tiorir,, Vol. 27, pzges 466-471i, G references Ju.ne 14-'+F< This experimental study e:<._tmined tt'hF t.o:,icit.v of propylene glycol. In rats the acute Average Fatali Dose of propylene glycol was f,ournd to be 33.5 gm per kg rra:lly,, 22.5 g+i7i subcutaneously, 14', gm i ntramirscul ar-..l y andl d_0 gm i ntravenousl' y. These f i gurres are i n agr eernent with those reported b,•y othe r authors, with the exception ofl the intravenous fatal dose, which issc,merMtia:t less than half that reported~by other _:uthors. In rabbits the acute Average Fatal Dose on i ntravenours admi ni strat i o'n was f ound to be 6.5 gm per k;g. The chronic toxicity of propylene glycol was studied,by the ad'ministra.tion of' the material to gr owing rats by way of' their drin4::i:ng-wa.ter. Concentrations of •T% or less caused no appreciable change in rate of gr-owth. A concenr- trati on of 10% caused' a temporary sl owi ng, i n rate of gr-owtih whi ch lasted f or about ten days. Rate of growth af ter thi s i cri ti al. sl owi ng became essenti al l y-normal.l . No si gp-ri. f i ca.nt changes were found on, microscopic e:aamination~ of organs of these animals sacr i. f i cAd at the end of the e:rper-i menta:l per i od of 100 days. Hematurri a was observed f'o7. 1 owi ng the i ntravenours admi ni stra:ti crn of sublethal doses of propyl ene g,l ycol to rats. Hrmolysis was produced in vitro by both diethylene glycol and: prop l ene cill ycol i n~ concentrat i ons greater than 0.14 mol zr . This in vitro action seenns to be due to the dilution of isosmotilc sodium chloride solution with the osmotically inactive glycol solution* rather than to-a specific hemolytic action of these glycols in the dilutions used. 1 ti i 7'/ 29 0021162 "P+i I OSH-000b iT'00 Chroni.c Toxicities of Propylene C+lycol, Ethylene Glycol, Diethyl ene Gl ycol , Ethylene Gl ycol 1"onoet.hyl Ether andl Di: ethyl ene Gl ycol h'tonoethyl. Ether lilorris, H., J., A. A., Nel son„ and H. O. Calvery Journal ofl Industrial H+ygiene and Toxicology, Vol. 24, No. 8', page 158, 1 reference October 1S'4: Chronic toxi.citi:cs of propylenre glycol , ethyliene gl'ycol,. di et'hyllene gl ycol , ett-ryl ene glycol monoethyl ether, and di ethyl erre glycol monoethyl. ether have been experimentally determined in rats. Rats were gi ven the compounds (1-:' percent i n thci r dietsh for two years. Propylene glycol did no apparent harm. Ethylene glycol and diethylene glycol prc,durced's numerours kidney stones which consisted principally of calcium o.:alate., At'rout two-thi rdls of the rats recei vi ng ethyl ene gllycol' monoethyl ether showed marked testicular enlarg,ement, edema4 andl tw.bular atrophy. This condition occurred', less frequently in the groutp, given diethylene glycol monoethyl ether, and onlyy occasionally ~ in~ the other experimental groups. (Only an abstract excerpted from Chemical' Abstracts is presented in the Journal of Industrial ~y. ' Hygiene and Tc,,<icology;' the original article appeared in the bA Journ_il of F'har ma.cology, Vol. 74, i.S?4=. ) Cj O 6Ca
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] 9 / ' ,' ,a=> . 0'f..,20959 N'IOSH-(DOi=)6r:).79(:) To;:ic:i'ty, Fats and Excretion of Propylene Glycol and' Some Other. 1vcoTs Hanz1 iE.;, P. J., W. W. Newman, W. Van WinkTe, Jr., A. J'. Lehman, /a. n c{ Iv . I<:, f;:: e nn e d y Journal o-F Pharmacology andlErperimental Tt'~~~er apeurtics, Vol. 67, pages U01-i i.: , 6 references September 1939' Experimental studies were made on animaTs to determine the toxicity, fate, and excretion of propylene ctlycol as well as to dotErmi ne the toxi ci ty of other gl!ycol s. Very 1 a.rge doses of propylene glycol andid'i propylene g1 ycol act as centrall nervous depressants; these glycols are devoid of demon- strable toxicity when administered in smaTler-„ thougK still large, doses for prolonged periods. While large single doses of ethylene glycol and di'ethyliene glycol lack the central depressant action, repeated'' moderate doses of these glycols cause mar Ei:ed degenerati on of the 1' i ver and k:i dneys wi tKa. fatal outcome. Accordingly, only the propylene glycol is suitable,, at present, for internal or systemic use withiflood and medicinal products, wi thouit d'emonstre aabl e hazardls to heal th. The di propyl ene glycol merits further investigation.
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19/7/33 i~0 1' ['~ 6 6 N 3: O6Nf00Cr:.,,?2q _,4 The Teratogenic A~ction of Propyliene G1yQol (F'r-opanediol-1,?) and Propanediiol:-1,= in the Ch~ic4i; Embryo Debhardt, P. 0. E. Tierratol ogy, Vol. 1, No, 2, pages 15=-161 ,3c: ref erences 1968 Uescr-ibes an". experimental study in which a comparison was made between the effect of introducing propylene glycol into the yolk sac and into the air chamber oudifferent days of devel opment. When it was f ound that. r'y5 r=r0 ml of the sol vent injected into the air chamber was, highly toxic f'or- the four-day- old embryo it was decided totest other related gllycols in a similar manner. When 0„05-ml propylene glycol or a related glycol was introd.uced into the air chamber during,early development most chick embryos survived the treatment. When a glycol was injected on the secondday of incubation or later the viability of ' the embryos was reduced. A maximal sensitivity towards glycolss was observed on the fourth day of development, when 90% of the embryos d'.i ed wi thi n two hours and :'0'/.' of the survi ving embryos had asymmetric malformations of'the limbs. OT all the compounds tested in the air chamber, only propanediol-1,3caused a specific type of malformation ('micromel'iah in a:~hi'gh percentage of the embryos, When injections weremade ~nto the yolk sac it was found that the insertion of a needle prior to i~ncubntion caused a high mortality even in the control'.s. This sensitivity towards a mechanical disturbance diminished rapidly after 24 hours of~ incubation. With the e:,cception of propanedioli-1,:'' none of the gl ycol Q appeared to be teratogenic when i n jected! i nto the yol k sac i n amounts not e„ceed'i ng 0.05 m1 . When r~=1. 2 ml propyl ene gl ycol was i ntrod'ucedi nto the yo1 F•: on the f oa!rth day of' incubation, a large lliqiixd'-containing cyst was observed oni the dorsal si de of marry of the embr. yos. The hi gh to.; i ci ty of glycols when injected'into the air chamber on the fourth day may be attributed' to their capacity oT destroying the vascular system of the yolk sac.
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1,.,, r ,,,.-•L;, 0 ii1; a'i:'1 N110S}-f--00012681 The in f l uence of F~'ropyl ene Gl ycol on pH of the Ga~.~troi ntest i rral Tract and the Incidence ofl Ceci Abnor-malities in Proil~er- Chicks B'owem , T. E. „ and F'. W!. Wal drourp Poultry Science, Vol. 48, pages 608-613, pages 608-G1T, ~'i ref erEncF,s March 1969 Ftcpe.,rt of expc•rirnents conducted to determine if the inclusion of propylene glycol in the diet of broiler chicks wow.l d=il ter t.he pH ofl the di gestive tract a.nd' to seE i f the addition of higher levels of tra.ce miner--al supplementation a:OU1 ci ai d ii n over-com i n g r_F rt= i. n hock and toe di sorriers. Data indicate that feedling, propylene glycol to broiler chicks resul ts i n nn abnormal toe di.=_order, , expressed by an outward curling of the toes. 4lcvel of `r"/% propylene glycol significantly increases the pH of the ileum and the large intestine. Chicks f ed a di et wi th 1 0;; propyl ene g,1 ycol show an i ncreased i l etrm pH but aa decreased pH in the large intestine, possibly due to increased' bacterial fermentation. The addition of increased le+eels- of i ron,, ziinc, or a: commercial trace mineral premix to the diet has 1 i'tt.le effect on the eccur-rence of propylene gllycol i ndLrcedi l eg abnormal i t i es. I ncrea5i ng the l evel o#' prropyl erre glycol in the diet significantly increases the incidence ofl t.he Ieg disorders, suggesting some derangement of' borne or cartilage metat±!ol i sm. 19/7/36 00tiE,8i2 t'UI'OSH-00017877 Methyl CCNU (NSC-95 4417: Toxicity of a Single I.V. Infursion in Dogs.. Vehi cl e^0% Absol ute Al cohol - 8t:r % Fropyl ene Gl ycol! t=leischma:nn, R. lr!. , U. HI. Scha:eppi, H'. f,•bsenkra.ntz, I. A. Heyman, V. IliievGE-:y, R'. F"•hel.'an, 7?. A. Cooney, arrd' R. D. Davis Department of Pharmalology and Toxicology, Mason Research Institutte, Worcester, Massachusetts, 50 pageoh1ly 5, 1972 Pharmacological evaluation of methyl-CCNU, an antineoplastic agent, i n 11r_,> sex paiired' doss wi tfi si ngl e doses 04 14, 9. -T: , 6. 25,1 3.12 and 11. 56mi l 1 i gr-ams per k:i 1 ogra.m i ntr_.venousl y infused in" y:er% ethanol - E?0% propylene glycol over a period of 2 to 29 ' minutes. The corncentra.ti:on of the formul'ation~ was 05.: milligrams per milliliter. Irreversible clinical, hemato- loUica.l., and pat.ho9.ogi:cal changes occucred' only in the 2 dogs treated' wi.'th 14 mil l i gr-a:ms per ti:i l ogr-am whi ch dii ed orr days 9 and' 10. Severe hema,topoietic toxici:+.y manifested by 1euF:openia, neot:ropenia, lymphopenia, severe bone marrow hypoplasica a.ndl l.lvmphoi d' atrophy 1 ed to ba:cteremil a, with necrot.i 4 i ng tonsil l i. t is focalf f i br-i no--hemorrrhagi c pneutmoni a, acute phl eb i ti s at in ie.ction sites and cardiac va,.l vuul iti s. Doqs on lower doses surrvived aind' showed no gross or histopathological changes att the necropsy on days 49 to 59. Slight and reversible toxicity included anemi,a, lymphopenia and neutropenia. Moderate reversible neu!tropeniz occured at doses as 1ow, as 1.56 milli- grams per kilogram. Primary toxicity affected' myel.opoiesis acrd lymphopoiesis. Survivors e;;hibited no hepatic to..i.city. . 874913bi7
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I I 19.'7.3B 0(.)05675 NIflSH-00017828 CCNW (NSC-79 c7"'7) : To:; i cii t y of a Si ng'l e I. u. Inf usi on i n Dogs. Vehicle: F'ropylene Glycol S0::, Ethanol 20"/. F].eischman„ R. W. , lJ'. H. Schaepi?i, D. A. Cooney, and R. D. Davis Laboratory of Toxicology, National Cancer Iinsti'tute, National I'nst i tutes of H'eal th , Pub]: i c Heal th Servi ce, Department of' HEa:l th Edr_rcati on and Wel f are,, Report No. hFR.'I-CCi i5-72-17, 65 pa.g;es May ].7, 19Z:' . Fharmacol!ogica1 evaluation of' CCNU (1-(:"-cF-rloroethyL)-?-cycllo- hFxy]J-1-nit- roso urea), an antineoplastic agent, in dogs with si nglie intravenous doses of 10, 5, 2. 5, 1.25, and 0.625 mi I 1 iigrams per El;i l ogram in ir:r% ethanol-Sc=N% propyy ene gl ycoli . Dogs treatEd' with 10mi l L igrams per k:.iilogrram dlied an days 1r'.r and 12 and i of 3 treated wi th"5mi 1 1! i grams per f•<i 1 ogram was sacr i f'i ced mor i bund on day 16. Severe hematopoiietic toxicity Tedlto necrotizing tonsillitis, food pad ulceration and necrosis, acute bronchitis and pneumonia. In surviving,dogs treated with 5 milligrams per kilogram or less and sacrificed on days 90 to 1r?fr all blood changes r-egressed' with the exception of slightly elevated ter-mi nal val ues f'or serum gil utami c-o:;aL aceti c transaminase and serum glutamic-pyruvic transaminase in 2 dogs treated with S'5 milligrams per kilogram. Survivors showed no gross or histopatho- logical lesions. The highest non-to:•ic dose was r:i.625 milligrams per t;i l ogram. investigated in Charles-Fiiver-CD-rats. Groups of 301male and ?~~=r female weenling rats were fedl for-. 2 years on diets containing 6,250 to 501000 parts per million (ppm) of propylene-gliycol. The treatments had no effect on mortality, body weight gain, fo!od consumption, hematology, urinary cell excretion, the urine concentrating ability of the E;idnEys, organ weights or pathological findir,gs. In a parallel short term study in groups of 15 males and 15 ' females f'ed 0 or C0,c_r0r_)ppm propylene-glycol in the diet f'or 15 weeks, hematological indices, serum and urine anaI yses andl organ wei gt~-~ts were compa,rabl e i n the control and test groups. No carcinogenic effects were noted, even at the I-riohest dose. The authors conclude that the no effect dose of propylene-•glycol is 50,000ppm, equiva1ent to an intake of approximately 2.5 grams per kilogram per day. Gaunt, I. F., F. M. B. Carpanini, P. Grasso, and' A. B. 6. Lansdown Food and Cosmetics Toxicology, Vol. 10, Mo. 2, pages 1-16i', 22' references 1972- CODEN: FCTXAV' The chronic toxic effects of pr'opylene-gllycol (57556) were ,Long-term To.<i ci ty of FropyTene Gl ycol e i n Rats 2?l7/1 5 Qt>S23Cr7 N'IOSH-00111 173
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TOXICOLOGY INFORMATI'ON ONLINE~ ~ ~ o IIJATIONAL LIBRARY OF MEDICINE © SPECIALIZED INFORMATION SERVICES TOXICOLOGY INIFORMATION' R'ROG RAMI ¢p
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1 I'NTIR'aDUCTION, The TOXLINE (TOXicology onLINE)database is the National Library of, M'edicine's online; inrteractive collection of'toxicoiogical information containing references to published human and animalltoxicity studies, effects of environmental chemicals and pollutants, adverse drug reactions and analytical methodology. The d'atabase consists of three files, TOXLINE, TOXBACK74;, and TOXBACK65. Currently the TOXLINE' file contains rect rds with a primary date of publication of 1979 to present. TOXLINE is updated monthiy and l contains full' bibliographic citations, almost all with abstracts and/or indexing terms; and: Chemical l Abstracts Service (CAS)~ Registry: Numbers. TOXLINE expands at the rate of approximately 140,000 recorda per year. There are approximately 862,000' references too older information (primary date of pubiication! prior to 1979) in TOXLINE backfilles (TOXBACK65, TOXBACK74): The NLM Automatic Selective Dissemination of Information (SDI), facility, is available to, TOXLIN!EE users. STORESEARCHES may be input, then requested~ with, an "Automatic SDI Request Porm". See: the ONLINE user's guide: TOXLINE information i is derived i from, five major secondary sources (y -5) and six special collections (6-1i 1)i of material. The component subfiies inciuded' in TOXLINE and its backfiles are: 1. Chemical Abstracts Service: Chemical-Biological Activities (CBAC). Chemical Abstracts (CA) sections 10'1'-105, 1G3; 159, , 160, 162=164, Sections 114, 1171, 1'18„ 161, 171 since 1'9821. 2. BioSci'ences Information Service: Abstracts on Health Effects of'fnvironmental'Pollutants (HEEP);, from 1972. 3', American Society of' Hospital! Pharmacists: International Pharniaceutical' Abstracts (IPA); from, 1i970. 4.. National Library of' Medicine: Toxicity Bibliography (TOXBIB), from 1968'. 5, Environmental Protection Agency: Pesticides Abstracts, (formerly Health i Aspects of~ Pesticides Abstracf Bulletin) (PESTAB, formerly HAPAB) from 1968L1981I. 6. Environmental'MUtagenlnformation Center(Et1i9IC)file, Oak Ridge National Laboratory, from 19501 all in TOXLINE. 7. Environmental Teratology Information Center (ETIC)', fiie, Oak: Ridge~ National Laboratory, from 1950, all in TOXLINE.. 8. Smithsonian Science Information Exchange: Toxicology/Ef;idemiology Research Projects (RPROJ), from 1979. 9. National Technical Inf'ormation Service: Toxicology Document and Darta: Depository (TD3), all ini '. TOXLINE„ beginni'ng 1979. ~ ~ ;t. 10. Hayes File on Pesticides (HAxES), 1940-t968 in TOXBACK65. 11. Toxic M'aterials Informatfion Center (TMIC) fiie; Oak Ridge National! Laboratory. 1940-1973' in TOXBACK65. W d.7i O
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NLM' TECMNICAL B!ULLETlN - M'AY 85 TOxLI'N~E UNIT RECORD The unit record in TOWNE consists of twenty-siix (26:), data el'ements. Each ils identifiable to ELIiILL by a two or three character mnemonic. While the record length is fixed,, the data el'ement lengths are varilable. Some records have multiple occurre~ncesofcertainidataiellementsandsomerecbrds do notcontain every data element. Each element can be searchable, printable, or both. The table below iind~icates the basic characteristics of the available,data ellements. TOXLINE UNIT RECORD' a PRINT OP'TIONS SEARCH STATUS TV DATA ELEMENT Abstract MNEM' AB' S D - F U~ X G L X A R X' Address AD' - X X * Author AU X X X X *' Award Type AW - - X * CIassffication Code CC' - - X * Coden CD' - - X' *„TW, * Corporate Name Country or State CN C'Y' X - X - X X X * Data Tags D'TG - - X *,R Entry Month EM' - - X * Identification Number I'D - - X' * International Standard. Seriiai Number IS - - X' *JW Keyword's KW - - X' * Language. LA - X X Order Number OD - X X. Price PR - X X * Pubii'cation Type PT - - X * CAS Registry Number RN - - X' * Supporting Agency Secondary Source ID SA. S'I X, X X X X X X. X. Sowrce. S0 X X X X TW' Titl'~.e Initiall Year TI 1F1 X - X - X X X ~ Fina,1 Year Y2 - - X. bDb (01 *,R Year (part of Source Field)i YR' - - - ~ * Zip Code ZP - - X M-~+r N * indicates the element i1s dilrectly searchable TW indicates the element i1s textracted and is searchable via Text Words R indicates the el'ement is rangeable ON
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1 AU - F;eed' k<.Ad C-iU -- Ya l k: ows Ek: y SH A D' - Dep. Rharm. Sci. ,, Univ. Arizona, Tur_son TII - Lys-:-xs of human red. blood c'el ].s, i n the Pr"e_,kence of various cosolver:ts S 1 - CA/1'0^l214502P SO' - J. Parenter. Sci. Technc,l. , VOL -2~9', ISS 2, 1i9$5,64-8 A~~ -- CBAC COF'YRIGHT: CHEM' ABS Two' in vitro methods are presented which enabl'.e~ the evaliuation of virtually any soln. for the prodn..-of 1;:,is in i-m. and i.v. administration. These methods differ from the std. hemo1ytic method in that the red bl'ood cell.s ('Ft~BCs) and ghosts, which remain after mixing test soln. with RBCs, are washed wi th normal sal i ne. The i ntact RBCs are then 1 ysed wi th water. Since the'f'inal' measurement is al'ways made in pure water,, the effec.ts of vehicle components on the absorbance or soly. of' Hb are~viir±ually eliminated. These methods were used to evaluatc propyl ene g;l' ycol (pG) Q W7-5W-6] , DM'SO C 67-68+-5] ,, EtOH r64-17-5],, polyethylene glycol C2S=.'22'-68-3] 400, (PEG 4D;i_r), dimeth.yl acetami die (DM'A )' [' 1 27--19'-5 ], and'idli methyl i sosorb i de (DMI) [53c=)6-85-47 or hemolytic po:tentiial' in comparison to a ref. of 1=o% E•tOl-l, 4'0'/. F`G, and 50%, water. Measured LDS0 values for lysis of FBCS are expressed as _total vol. percent of cosolvent ir whole blood. These values are: '9.5Y,Dh1'I, 37.{>Y.I DMA, 30.0% PEG q'.(ic)„ 2i'.2% EtOH,i 10.3% ref .,, 5. 7"/" ' F'r, and 5. 1% DMSO'. 2 AU - WAHLBERG JE AD - Dep. Occupational Dermatrlogy, }:::arolinsL<a SjuE;huset, S-1C.14 01 S`i:oc(::holm, Swed'. TI - Erythema-inducing effects of solvents following epicutaneous a:dmi ni strati ontomanz Stud'~i ed by laser D'opp 1!erf l owmetry. S I' HEEF'!05'1'028901 SO - SCAND J WORK ENVIRON H'EALTH; 10 (1=)1. 1984. 1 59-162'. AB - HEEP C(?F'Yfr:IGHT: BIOL ABS., ^k;in exposure to solvents can cause erythema, edema, scaliing, and, e•<entuaTl'y, irritant contact d'ern?atitis. The irritant potential of chemicals is usually assessed by vi sual scori ng, but i rr recent years a more ob jecti ve measuring technique, laser Doppler flowmetry (LDE)', has been 1 ntroduced for the assessment of er--ythema. The method i s noninvasive and' allows continuous recordingi. Ini the: present stud;. 11 solvents were applied for : 5 min to the~ volar- Torearms of aa m an and' the kinetics of the response is shor.on,. For 7' solvents: (dimethyl sulfoi<ide~, tr-ich.loroethylene, n-he:.ane, C C14, to1uene, i, 1I, 1' trichlor-aethane, i, 1,<--tric_hloroethane:! an increase l<,as found over the pretreatment value.s,, whereas 4 solvents (methyl ethyl ketone, ethanol,, propylene glycol, di,ti11'.='d water) did not in-fl!renCe blood flow. The~ •findin'qs are discussed in ,-Platiion to the macroscopic picture (whit•-_ni ng, and" er-ythema.) andl in relation to p,r_e-uious studies ofl the edemr,.-iinr!>>.cing effects ~~fl -the same sol v~~~nts on man and experi mental ani m t1 s. LDF i s wel 1 worth trying in cases of marginal irr-i tancy andd for predi ctive testing „ si nc-_ it t seems to be more sens;. ti ve and rel i abl e than the naked 87491312
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AU1 JAU U AUl AU AD TI SI sO LA A B h-9 i 11 e r- RR hterrrrann EA Young JT L_a.ndr-y TD Ca1 houn LL ~ , To.sicol. Res. Lab. , Dow Chem. U. S. A. , h16.d'• and~ ~ Ethylene glycol monomethyl ether and propylene glycol monomethyl { ether: metabolism, disposition, and subchronic inhalatio !n to:; i ci t. y:. st ud i es I - CA110?/Cr19c=)45tr! ~ - EHFF, Envilron. Health F'erspect. qVOL 57,, 1984,^. 'T-9 + - EhIG - CBAC COF'YFIGHT: CHEM ABS Short-term and subchronic vapor II inhalation studies in rats and'rabbits showed'that there are , pronounced dif+erences in the to.<icol. properties of ethylene (. glycol ,nonomethyll ether (EGME), C1c79-S6-4] and propylene glycoli ( monomethyl ether (F'GME) ' C 1=L0-h7-S7 . Overexposure to EGME l~. resulted iniadverse effects on testes, bone marrow and lymphoid~ i tissues in lab. animals. PGME does not af fect these tissues, andl i nstead~, overexposure to PGME was assocdl. wi th ilncreases iin I i ver`. wt . and centrz.l' nervous system depressi on. EGME is pri mari l y o::id'iL ed to methoxyacetic acid . C6C5-45-61 in male rats, whereas ; F'Gi"IE apparer.tl y undergoes O demethyl at i,on to:propyl ene g,li ycol [S7-JJ-6). Since methoxyacetic acid has been shown to have thin same spectrum of toxicity as EGNE in male rats, the obsd. differences: in, the to::,i:col, properties af EGME and PSME are thought to be due to the fact that the 2 materials are biotr-ansformed' via different routes toldifferent types of metabolites.
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4'. AU' - I"I'i 1 1 ter R AU - Herm.EAnn EP! :~. . ~,. Iti `-~ T~. 1It.1 n(7 k _~ AU - Ca1 hc.,u'n t-i~~:- F1 1' s t 1 i.."P F1L~ -''icc~l !~te s. t.:-ab., Dow Chem. IiC4, !'lidland so LPi A'i.' Propylene glycol monomethyl ether acetate iiFIGMEA') rretabol ism, dispo,,ition, and short-term vapor inhalation toX.icitv studies i~a / 11: t-i f /':'t i 5- 5-5- 40 To:,icol. Appll. F't,armacol., VOL 75, ISS :3, 1984R15:'1-?01 ENG - CEir;C CCrF',F:IGi-{Ta CHEM ABS Male rats were given asi~ing1A oral dose of appr::.8.7 mmo,l/F::g of 1-14C labeled PGMEA C1i?G-65-6] or exposed to 3000 ppm C1;-14C]F'Gh1EA for 6 h. After dosing, expired air, excreta, and tissues were analyzed' for 14C activity, and metabolites in urine were isoliated and identified. Approx. 64% of the administered 14C activity was elimina:ted' as 14CO2 and appr :~''}'% was excreted in urilne within 48 h after a single oral doGe of ra.diolatieled PGMEA. Similarly, 53% was eliminated as 14CO2 and 26% was e:ccrreted' in urine within 48 hi after the inhalation exposure. Propylene glycol 157-55--67„ propylene glycol monomethyl ether (F'GM'E) C1:320-67-8'7I, and the PGME sulfate C85684-22-63 and PGME giluicucronide C85624-'23--7] were identified as urinary metabolites after oral, doaing, as wel.l as after- i nhalati on exposure to F'Gh1EA. The ur i nary metabol i te prof iil e and disposition of 114C]F'i;MEA were nearly identical to results previously obtained with F'GME, indicating that F'GMEA is rapidly and ~y,:tensivei~y hydrolyzed to PGME in vivo. A short-term vapor infialation toxicity sturdw in which male and female rats and rr;ice were exposed to i_i1a, :.;<;;iti, 11oxDo, or ::000 ppm F'GM'EA contir-med that there r-aer-e no substantial differences in the systemic eff'rct.s of F'GI11EA: as compared to F'Gh9'E. However, histopathol. e;,a:mn. did reveal changes jr the olfactory portions of the nasal f-jiucosa of rats and mice exposed to F'GMEA,, which may be related to HOAc resulting -frem h;.,dt-olysis of PGMEA in the nasal epitrieliurm.
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y!_l - 4~%,hlber-g IE' ND TT i!ep. Occu.p. Di=_rmatol . , insk:a Hosp. , Stockholm ecf; r_ts cf solvents falsOwlnq, er ;lctkt.?.ne.7uls r~~~,n -- st~~d'.ied by laser Doppler flosvrr~etry Scand. J. WorEi:, Environ. ENG - i_ryt hefil'c?-•Z,ndLt-- ,1 ng adf -ni ni st r- ,--At i on to C(a! 1t11111Ir0'r;61:1 Health; VOL 10',, 1S-S 3, 1984, 159-62 CEAC COF'YF'IiOHT: CHEht F1~BS usuall y assessed'; by vi sc!al' The i rri tant potenti al of chems, i s I scoring, but the laser Doppler I Y 1owrnetry (LDF) was introduced •For the assessment of erythema. I The rnethodi is noninvasive and allows contin!rous record'ingi. l Flevenisolvents were applied for .ltor.Eq.5 min to the volar ~ f oi-earms of a man and'~ the k:i neti cs of the response i s shown. For'[. 7 solvents (,Di"5O': C67-68-57, trichloroethylene C79=i>1-6], hesaneli C 110-54-3], CC14' [56--•23-3-5']', toluene C1iy8-88-3], 1,1,1-tt ichlor-oethane 17'1'-W5-6]1, 11,1,2Ltrichloroethane C7 l-0c_r-O] ), an: incre se was foarnd' over- the pretreatment valiues, whereas 4solvents (Me Et ketone C78'-93-:'',]'„ E'tOH'. C641-i.7-5], propylene glycol C57-5,5-67, distd. water-Y did not influence blood flow., The findings are discussedlin relation to the macroscopic picture (whitening and erythema) and in relation to trying.in cases of marginal irritancy and for predictive testing,i since i t seems to be more sensi ti ve and rel i abl e than the nak.ed eye, previous studies: the edema-inducing effects of the same solvents on man and exptl. animal3. Thus, LDF is well worth
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t (I~ ~ C V I AU Ai_ I AIJ 17 1 -- (~_; I L E JD •- F9E'rA'%'E' ; .113 F I KI-:. 4; T•-!E LFF-r ECT OF '~~CHEf11I CAL, Crit+:F: I r F-iS C+t-4 AVI F=-tt.`~~•! Lt:--5t~=7 Tf=! XI C I TY TESTS ' SI 11 F_=F"/ >C41/ r:, u6Ca7' SO LLf) BULL cl`•lVIFtOhF CONTAIM TOXICOLq ~'1 ('), ., IV83'. 190 •02'. - ENJ FIB -HEE!P COF'YFiIGHT: BIOL AEa.; RRM r!1 JAIIL DUC~:: PEBTICIDE FOOD CHAIN 'i O'AIC S!JB{iTt?hd'CES~ COhdTROL ACT W ;A 7 AU AU AU AU AU AD -_ ^11 l l er F R - ~~~-1Qrmann EA - Langvardt PW - Mct`>•.enna MJ - Schwetz BA - fo::i'co1. Res. ab. „ Dow Chem. 8»i9 Midland TI - Co~~par~+:tive' metabolism and disposition of ethylene glyco'l monomethyl ether and propylene gliycol' monomethyl ether in~ male r a ts SI . - CA/09&/152854/Z- SO -. Toxicol. App1. F'harmacol.; VOL 67, I'88 2, 198-',2^G-37 LA - EhlG AE, -- CBAC COPYRIGHT: CHEM ABS ADDENDUM There were pronounced : . „ p py g yco ('11,22-propanedioL) C57=-55-67, and the sulfate and glucuronide con i±igates of F•GM'E' were identified in urine oE rats glivern PGME. Since tll'e:.tho::'y%tt=etlc c!c'i'd causes the saiiie Spe't_t'rLtffi of t'o}:',IcIty a5 E'rME, i t is l i E::e1_ y t`_hat the dver= = ef f er_-t s, o7"r' EGME are the r:_-esuit of~ a'ts' metab. to methoxyacetic acid. Differences inl routes of metjab- and types of metabol: i~t• s appear to be the under!-l•,rin,_a b.asii_ -for the mar~::edly _lif,:,~•rrent to~<.icol. proper~tiles EGME a:nd PGME. di'fferences in' the met~xb', andl disposition r-;f 141C-l<abel:ed ethyle-n'e; gl ycol monomethyl ether ('EGME')C 10y 86-47 or propylene glycol monometfoyll ether (PGME) C1'20-67-87 by rats given a si'lnyle orra:ci ;' ciose (1 or 8.. 7 mmol /t::g). Appt-o::. 50-6i)% of the admi rni stered 14C : was e:kcretedl in urine, and appr .1'`?% was eli'minated as 14C0:.' twithin 48 h o•f administration of EGMi=. For F'GME, only 1t~y•-i0% of ; the administered' 14C was excreted in ur-inea and' O<:i-60% was eiimd'nated as 14CD2 within 48' h. Mbtho::yacetic acid E625-45-6] ~ Was the pr-i mary ur'i nary met abol i tf= of EGME, account i ng f or- 8Ci-9o%{ of thetotal 1'4' C in urine PGME ro Tene l (1
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Hi'''_; - ;`1Ii-LE~~ f"f, Aii1 +1i - Lri t<aG 'v'A R'r,T F-1 4 . ;a'uI , 'y~!j AD T I' S"Il SO'1 i`irl-;ca',iN i-i N-J _ ..[_] 14.iJ==:T-, ~..'F': - Tr_;:;~r_Ll.r..y ny_;:;~r_Ll.r..yn y_Ll.r..yny Research Lab., Health c,n'd'' ;_nv'1i r_+nment'al Sciences USA, Dow Chem LISA Mid la nd! M'ici't 4S64C? - ., , , . , . . Cc;mpar-a':-e i ve metabol' i smi and di ;p,osi t i on' of ethyl ene gl ycol. - mannme,..l ri•-~ l ether and propyl ene gl ycol monometYiyl' ether i n r eS t..: ,.( FiEEF'J'c~4/ i_;;~;:1;2. ti maT e - T'Oh Lz :OL APF^L F'HAf;IIiiACOL; 67 (2). 1993. LA -- ENG A'i' - HEEP' CGF`4`R'I'GHT: RlOLL AEsS, Male' f=i'scher 344 rats were given a sinq,le oral dose of' ' 1 or 8.7 mmol/E::g of (14C)EGME' (ethyl!ene glycol monomethyll ether) or (J:4C)PGME {propylene gLyQol monometlrMl etheri. After dosing, e:;pir-edl a'ir, excreta and tiissue=_I: wer-e' ._sn_all•Jzed' for 14C, metabolites in urine were isolated and identified. There were pronounced differences in the metabol''.ism and di sposi ti c,n, of (;'4r)EGME and ( 14C)f:'GME. Appro;, i matel y 50 to, 60X o-F the' administered 14C' was e„creted'in urine, and about 12'J% was el iimi nated as 1'4'C0-71 withi n 48 hi af te.r a=i ngl e orall dose of (1.41C)EGME. For F•GME, only 10 tW 2'r-r"/.' o+ +..he a.dmin'istered 14C was e_cr-eted in, urine, while 50 to 61'.,%w=.4.s elininated as 14C0:" within 4S h. MetYiox:yaceti:,:< a.tid was identi'fiiad ~,:s the prrimary urinary metabolite of EGME, ai_:=cntnting for- 80 to 9!i% of the totall 14C in uriine. FGME,, propylene glycol ( i',:='--propa'nediiol' ) , and the suD-'Fate and glucuroni'de conjugates oF 'PGME were identified in urine of rats given F'GME. Since methoxyacetic acid' causes the' sajme spectrum of toxicity as, EGME in male rats, the adverse effects of EGME are probab'1y the' result of its in viivo bioactivatiion to, methoxyacetic acid. f-lence, di+f'erencea ;:n routes of inetabolisRi and~ types .~-f ' metabol'it.es appear to be the underlying basis for the rema.rk;a.bly iif'feren't to;cicol_gic piroperties of' EGME and PGME, respectively.
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. 9 AU Oile JD AU AU t:_ f_'a•' c2 ir J1 F i. nf<; fZ A1 Cor'='cil.I l.s. Rei5. Lc+•b'.,. E.nvi ran'... i'rat. i2g*'?ncy, Coh-v_Ul.llL.s TI Th i_ i=f-i`'e=a_ [=h efi!]. =•=ai, t=_.7 '., 1 i-ar_s' an c+.viii3n i_r.'i(-')i to.' 1',!_ .'t J ^' I CA .•' <; `> 9-' j.. 0-? i'= 4 1.' Q C-:0 Bull. Fnvirroni., Contam. T'o:;i col . 4 VOL ?1, ISS ~, 1,'8=,,19a ~`0:' L ; EN G I- AF I CDAC COP`iRIOF! T: CHEM ABS The use a-F corn oi l, propyUene gliycol CJ7-.°-,5-h-I, i=:1`1-cellUlose C90tr4-32-41] andi 1-4-'0 as carriers of the pesticides carbofuran (I) C15 6 '--6 ('M' -'], du r-sb,-Tk n Cy921-88-.%']' and 1() A'Ui AU AU' AU Au ^U AD endt-iln C7 2--2~~~:y--0] iin d'ietarrv st!idies witth bobwt-ri,te quails and mallard duci;:s showed that carriers hnd an effect on median lethal concn. (LC5C?) values since dose--response curves changed with different carriers. W6:th few e:,ceptions,, groups of bilrds presented wi th corn oi l consumed l ess food than those presented', with the other 3carriers, but growth was not affected by r-educed' consumption. Anall. of feed samples indilcated no effect of any carrier orn test chem. concns, in feed. - Sinqh PP - Junnarr::ta.r AY - Sesha»i'r-iraol C - F::aushal F: - Nai dU h11.;R - et al - Dept. of' Fhar-macol. , Bi'ol., Uiv., , Res. C±r-. , Indlian Drugs and F'harmaceitt i cal s Ltd., Balanagar Tdwnsh i p, Hyd'erabad 500 0.'7 ,, Ind'i a - F'harmacol oqi cal study ot propMne-1,2-di ol aPAJ8'/ii6<:i7ir -Arzneim. rr--.rsch. ,VOL "2 ISS 11' 1982, F144'-1446, (REF L'2') - ENul - IPAi CC.IPYRIOF-ITa AOHFF' Neiiroto:<icologice•l eTHects ofl high concentrations (;0-10r_i"i.) of propylene g',lycol tpr-opane-1,2--diol i follow,in:j I!1-' or oral administration to a variety oz animal species are di_c,rssed. It was suggested that concentrations of . 1'ii% ,ar- less be used when propylene gLycoll is employed as ---A solventt in phar-riiacological or toxicological investigations dLee its potential for a.r_tivity.
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F`a r°'ts L ~'~on,.L ne DL Di. y-I-L_rn Lab., Monsanto F°es. Ci:_-r p. , I=1a•;•ton =I_!he-r'1.or h''c.t '•.=ran='t'er i I.''.uids -$•or'_ solar Ilhr_ttln':3, and •=oolirig :; p;pl1_atlons. i:f si!lt5 r-.7i B.cL.lt C', Clr. a1.ll tC}i,;lt ',l.t•.~ d+?t~rT._ii':3a1ci l{ SI SO -- Fit_por-t, ISS ~ I'IRC._.1TH-1c;t96,-Vo1.1;, Orrder- No. hE&:'ti027S8031 ,, 1'=:8 1,-b LH - ENr f`iD - C B F;C COF'YfiILl+IT: CHEIHi FAIBS r=}cUtF, ora.I toxicity tests Maere conducted in rats with .tiL hea:_ transfer fluids used in so1 ar collectors,, lncluding _fl?cidr ttiat h:=.d been usPd' in collector instal'lations for 1i-3 yr-. The t_,o=asellin acute oral to;;i!_i.ty ra.tings off the f1,_rids r-.anciG from 1 (practic€,I1)< nonto:-"ic) to = (moderatel y tox i c);' most f l ui ds are rated'. 1. Facci denital ingestion ofl LDs ils not very probable in normal use. B y Gna_el in 's rating system, u!ndI ld. ethylene gl!ycoli C107-'21-13-based. +luiids are classified as 2(slic_ahtlY to;<ic) 5. p'p- whereas propylene gliyeoll C57-55-6]'-based fluids are rated 1. The L!se of ethylene gl'ycol- and' propylene glycol-based fluids +or I yr„ and of an al'iph. hydrocartaon type fluid'. +or 3 yr, * increase their acute toxicity signi+icantly. d'i 1'. not 1 ^' A U - Nel son ED TI -- Method and corriposition -(or~.r reducing the toxicity r-;r acetamin'ophen SI SO - C ;ic_y96/c°_r91-h74U -- h. S. PATENT hdU 4''. :0)707=: 1:'!' : 27/81 (State Ui-hi ve.r-si ty o-F New ' `,'cirk: v LA R•?,3earrch Foundation) Eldr AD - CE.AC COF'Y'F{I'uHTa CHEM AD S Ttie, toxicity o,V ~ acetaminophen (I) L1OiZ.-9t?-^7 is decreased by oral, s.,c., i.v. Or i::m.. administration of a mixt. of I and propylene glycol (II) C57-55~-67. (0.'-12 o- body wt. ). The rati~o~ of I I to I i,s !~, _-4crc_)~ . I (by wt. ). Other pharmac=e,!tical carriers or diluents can ae used with this mixt. Tliiirty mi /k:g ofi combined ' S II and 0. 9'L sal i.ne soi'n. ('li andl I I in var-ic,>_!s doses) wer e c,:.v*.=,n by i, p., i'n jecti on~ to whi te miice. The _cirvi val rate among 2-7` mii ce was 96'Y., measured at 96 h after d'r s<aale- ( I I-I rat i o, was 7. ;1.- 1) . I I does not seenl to have ca to::li c ='i-fe C%' -::!'nd does n o t didver==ly' a 'i fF_ct th nn<a.l~itsi:_ I.rroperties of I.
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Pr,OG: i AU' - I s h i. d la t e MJ' YY AU' - Sof un, i i T P rI W, T V,= 1 1 1 Kk cl Y9d: h•. AU - Hayash i N AU - hdohmi T I AU -- Sawada ht I AU - Matsr_roE:;a A AD - B'i oll. Saf . F`tes. • Cent ., h1atl. I nst . H•lyg. St i., Tokyo TIi - Primary mutagenicity screening of food additives currently used! i ri Japan ! SI - CA/101l209264N r SO - Food Chem. Toxi co1' .;' VOL 22, ISS 8, ~ 1984, /23-3& LA'i - ENS A8 - CDAC' COF`YR I OHT: CHEh1' ADS Plutagen i c i ty f ood~addli ti ve scr-eening; Anise Food additive, rnl~-etagK=nicity screening of; Apple !' Ex't., food additive, mutagenicity screening of';Beet Red pigment -'t from, foodl additive, mutagenicity screening of;Caramel Foo id addi:tive, mutagEnicity screening of i.olor;Ceratonia siligUa Foodl additive, multagenicity scr eening orf';Chlorella F'igment from, food' ; additive, mutagenicity screening of;iChl1or-ophyTlins Ir on--sodium sall•t,, food additive, mutagenicity screening o-F;Chlorophylls Food i add'itive, rnUtagenicity screening of;Cocoa F'igment from, food' additive, mutagenicity screening of,Coffee I-:;t. , mutagenicity scr-eeni ng, of ; Col a E:a't. , frnutagenici ty screeni rnig of' Genus;Food Additives, mutagenicity screening of;Oiils Lirne„ mutagenicity screening of,•,Oils Sage, mutagenicity screening of;Oils Clove, mutagenicity screening of;Oils Cumin, mutag;enicity screening of ; O'i 1's Lemon, mutageni ci ty scr-e=-.ni ng of ; Oi l s Oni on, mutageni ci ty screeni ng of ; Oi l s Thyme, mutageni c i ty screeni ng of ;,Oi 1 s hdutrneg, mutrzgenici'lty screening of;Oils Or-ange.,, mutagenicity screening' of;Oils Mustard', m!itagenicity screening of;Oils Perillla:, mutagenicity screening of;Oils Cor-iander„ rll_.itagenicit.y screening i of';Oil.!s Spearmint, mutagenicity screening of;Oils Grapefruit, ~ mutagenicity screening, o:f,,Oila Peppermint, mutagenicity screening~ of ;Oi.l<-- Cinnamon bark, muta.genicity scr-eening o";;='olyphospl-ioric ~ acids Sodium, food additive, mutagenicity screeni.ng of;Resin acids and Rosin acids Esters, foodl addlit_i ves cL)ntg., rmuta.geni eity screening of;Silo;;a:nes and Si.licones Resins, food additive, muta:gen~i cit.y sci~reeni ng of
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3 rhL1 -_ TOINGC. :1U - U,Iii_LIryi?1S Ci.i~'ii N1} Amer-ic::~.n F' 1~:'th ~+oL:rndlation, Navlor Dana : Inst:. D2is. F'revention,. V:g:l, h a_. i-. 1' a ,, NY 1 I_)ci>'` '., ILtSr-t '° . • . TI -- Di f fercr,c•= _•, i n responses of' 4' adul t r-at--I iver ep i tl iel_ ilal~~ cel I tines to, a spectrum of chemical mu~'_s.caen -5., SI HEEF'/94!'{i>9'-5-61? S Ct - MUTAT R%F_S; 1301 ('1) . 198''1. 5.':'-62. LA - ENr NE' -}-IEEF' CQFYhiGHITa BIOL ABS. An assay for rrrutagFenesi_ at the hypo;,e:mthane-guanine phosphoriGosyl transferrse (HVF'F'~T) Iocus in aduult r-at-liver epithelial cel.ll cultures (ARL) was: dleveloped too take sdvantageof the capaci ty of t h i s cel 1 type to metabol i ca1 1 y activate promutagens/procarcinogens. Aisur-vey of' the effect of' 5 types of -activatilon-d'ependent mutagens/carcinogens' (mycotorin, aminoaao dye, polycyciic aromatic hydr-ocarbon, nitrosamine,i aromatic amines and amides) on 4 ARL Iines (ARL--6, ARL-14, AFt-1J^o, A`:L-19) i ndi cates that the ARL/HGPRT mutagenesi s assay wi th ttle 4 target ~~_eI 1]. i nes i s abliee to detect a spectrum of activafi_ion-depen'dent carcinogens. Individual ARL lines, however, responded' quite' d'i fferently to _•.. given carcinagen. The ARL/H1iPF:T mutagenesis assay system thus offers distinct possibilities for- -the study of the control' of c/:-,ertrical bilotr-ansformation processes. In lig4ht of the specificity o-r~T the various celll lines to, respond to a po:rticular cl.ass of mut:µ.gens{:!r,dk.~nr the current assay cond';:tion, this particularr assay system cannot be readily applied to rQUtiin;= screening of suspectedl environmental mutagens of u.inr;nown r-c-quiremtnts: for metaboiic ar_tivation. For agents with, a str-uctui°-e rel at.ed to those acti vated by a speci f i c l i ne, thi s system ccribe ustd' to study rttUrcagenF,si _ r-e sul ti ng' ,f r-om i ntact c +?all'ulia;.~r me'l_abol,ism,. AU AW. AU' AU Ari' TI Ta,,l or .L Bergi CM Shopta:ugh NH I T'r.ai sm.~kn E Food fies. 7r,st., Univ. Wi.scon=in, M.disori ~ h'Pt-ttagen for mat:ior, in, dleep-f:zt fried f'oods a~ a -fun~:_tion of fr•!inc:: conditions GA/'09E3/'159-236F JAOCS, J. An7. Oil iJhem. Soc.; uLLL IGS'. 1':8-:, ;/6--Er-; Eha.r '1 CB~`~!:' t~:.~rF'YRIGHT~ G'F-1Et'9 ABS !'lut_igen, frying p~~L_to fish cn:i'.cn i.]iI mutagei; food frying;Cook-ing t.'hutagen for•-mation in fop -ds dur-i'ng, fr yinra conditic,ns effect on f r-ying;,t=:otton eEri c,il' Frying oiI I; contg., m!-ltacyen formatzon' in, food fried 1n,Flsh Muti-aqenlc activity of Fritd,, frying conditions effect on;hluta_aens F_,r-,r,ationli ,o'r, in 'i-rTed '#ood's,, frying condltlo,ns effect t7n;dh on MutaG"en1.c ctr"t1.`:•l,tv ;=i+f Yh•'iis'd',, irL'lnqconGiltlon'S F''ffec~'' ori;F'C~tctt.+.J I"I!ttcg,enlc' :.tctivi'_;1~• +~rf;rying conditions effect c7rr,Ta.llow Fryi:~~ oi'1 corrtg,.,, -formatiion, in -,•ood fried in 8'7491323
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,'. -~ ;U A_:$ S U r r-~-i~ + I~ t~;S SCE AS AN I'.NDEX I::1F h'IL:T'r'-tCiEtdI=SI~.-`-'-- AND/OR CARCINOGENESIS, Iha: S,ISTEF", C'raR 0 t'IA'T I D EX/C*tar=lt•1:_ E SI' - EC•1IC/8 2 /C~t_i.=,5 4 6 SO •- F'R.O& TOP CYTOGENET;I w': 4E)11-514, 11952 LA - ENS AD -- EMIC/ORNL SEE: CA, 97--50u-127' ' J AU - MARSHALL TC AU - CLARK CF' AU - BFtEWSTEFt' DWi AU - HENDEFt~SON' TR TI - TOXICOLOGICAL ASSESSMENT OF HEAT TRANSFER FLUIDS F`F:OF'OSED:FOF USE I N SOLAR ENERGY Aa 'PL I CAT I O':uS S P - ECYFI C/81 /0tj0241'. SO' - TOXICOL AF'F'L ('-'HAFttttACOL; 58:''1-_8, 1981 LA - ENS AB - Etf1IC/'OF'NL SEE:', CA 94-186461 6 AU - F-: E I Tt-t LH AU - HARLESS JM AU - WALTERS DB TI', - ANALYSIS AND STORAGE OF HAZARDOUS. ENUIRONMENTAL CHEMICALS FOFt' TOXICOLOGICAL TESTING Sl - HEEF'/S2lCi1'0_7 SO' - M'Ck;INNEY, J. D. ENVIhONMENTAL HEALTHI CHEM'I'STFiY: THE CHEMISTRY OF ENVIRONMENTAL AGENTS OF f`OTENTIAL HUMAN HAZAFDS; SYMF'OSIUI'f1 AT' THE' 178TH NATIONAL AMF_RICAN' CHEMICAL SOCIETY' IMEETING,, WASHIN6TON„ D. C. „ USA, SEF'r'T. 1..979. XIV-}656F'. ANN ARBOR SCIENCE F'tJE+LISHEFRS, INC.,: ANN ARBOR, t`11ICH., USA. ILLUS'. ISBN i_>-25040'52-8. ;, 0 (0) . 1981. F'S93-E22. LA - EIVr AD' - HEE'F' COF'YR I GF-+.T`: B'I OL AE:SS. HUMAN h°IUTAGEN OCt:.UF-'AT _ ONAL HEALTH' USA. NAT I ONAL TOXI COLOG~~~`r~ PROGRAM I
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Chen T {..{' TJ ~.'~il anq, CC Tr_.7.=~~:1<:o j4: n F'edi?'tr. . Inhibition of HM_;t11.. DiY:.v. M 'Ji r_i r1,gc4n ';t Ei tcD {Jritl East Lains'1Jiiin metabolic cooperation in Chinese ham7ter V79 cells by various or-ganic solvents and -;implc r_ompot_inds ti.f='+.`'1 0):]: t'C-? 17'5) 9 71' Cel lBi ol, To.',i coll . q VOL. i. r4lti l.i]r'.. I i., 1~'-+~841. 15 5 -7~.''1 ~.. CBAC CCF''Y'F;IGHT, C}-IE{'1' AB.S~ Gap Junctional intercell!.{l'ar- communication is a biol. pn ocess impl ic,--tted in the regulation of : cell proliferation and differentiation. Metabolic cooperation, ~ between,6-thioguanine-sensitiive and' -resistant Chinese hamster cel l s, i n vi trol, has been used as .-=k means to detect chem. which can inhibit this farm of :interce'llular communilca.tion. To further!! characterize this i n •.•io tro syste.rr as a potenti al screeni ng,assay for potenli' ia.l teratoc3ens, tumor promoters and reproduct i ve toxi cants, a ser i es of common, s ol ventr. as wei las other chems. representing 8 different functiona1 groups,, i.e,,, a:lcs., glycols, ketones, esters, ethpr s, phenoli•a, aTdehrydes, amines and amino compds. and 0-heterocyclic compds., were tested for their ability to inhibit colony--for-mation and to inhibit metabolic cooperatilon.. A ii.-iide range of effects were obsd',., which suggcsted a: structure-activity rellA'LionsF~~ii:p between zt chem'. `c- a.trility to iinhibit gap iunction-mer:Jiated interc_1lular- communication and the cytotoxicity of a chem. F'ossible mecha.nisms _a-ffecting the mod!!llation of g,^-p' Junctlonal C-ommL+.nic r:ti'on by these chems. are di scus_edl. ~ AU AU AU taU'' AU TI 4,I E:•EADAi_IGH V1;1 COLLINS TFX HOHE I c:E~tL CA BI EREtL1WER GW tYICLfiIJC?~•IL_IiU J RAT TERATOLOGY STUDY OF t'tR:=tLLY FiDh1IN:E'SiTEE-.EJ ; TFi',I S- {',,=-I] I E~~CfPr1F'FTiOF'`r"L'_ ) f HID:=iF I li ".TE ETIC/31 /0c:iti[:jCtE ~ SO' LA ~~ B t=UrJD C17,'-`-t"1ET TCY..IC0 L;' 1'IF w'6 7-7:I', a rc.11 E EN i.; ETIC/ORNL A STUDY W+3S LINDEF+'TA! EPil TO DE I"k.R1"II{?IE: THE TER'ATCCE_{;iIC ! FCTElt.{TIAL. ri= Tfr:IS_ {', ': ~iF_{FiQlit tf f'r~l `r'Li E N{_~CFN~3TE, (Trtz`" TH{ , f=1LJA{`il '_ fh.ElF~E-:~-~~'~NT r=DEa~IE=F'L4' USED it:! CLUTHI'1iJ[-i.,Tr~IS,,Ih I.1iJ[-i.,Tr~IS,,IhI .i.,Tr~IS,,IhI. !!II`~lDILL1Tr_t.~ i=F:Cti'r'11f=h1.E, ~ I f L`r'CGl , Wfl ~- s)(' ial L' :EI 1 f'Jr aaTl D ? f+ I r?, i{ E[iNF.h1l E EAGIJE= , 1=AtlL,- ("1AT`~ f_lN ~ I,l 1..-i nflGE SC yT. I t N F+ E' iti L} VF:L OF (),y °' ,: i rJR 1` h1Rc L+i'l`i , rr; ( r{.QL11' 0,- lJhITI~.E=i~TLL~ I L_tIfl'._I~`__ ._i[=F('vEL ta '13) ' Ea hiLtn(.TIVi_ C0t1'4lE,O'_ i iEf.OUF' WEI'CHf A1h1' DURING t TATICtf1 WAS CILbNI+7'IfW;hLT{_r T':IE=fZE_ili :I:1'•`~ . THA.r•l iC tA!_-S TF'E(a FEE, WI TE3 MCli t(/1}AY , UUT hd{_'' 0'I-'HE R ED Tox.IC' LtF 1!E:F4)TC6LI:IC c_H-F-ECTS WERE C'ERSEF,'.'E_D.. ~ f,b
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!ii ~hi U l~i; n ~. n q r~ i•;.__:~I't~lr, rk AU _. -:it:N-EA Fc-F{ i=~" hiU -' Cfq 'A. V C:_L. C F T F i Ei 1`1 {= r' %Ci 1F_MT CALS , Q?!`1' FtE;'riC'~uC i I ~`~' MALE (;hdL; FEM( iLE - F%raL!fi AG G\ r - rn..,r.--._ I i'va, -- - - Emerson DJ - Nichinson DE; - Dep. nadliat. Ther.,, Harvard Medl.=ch. Y Bost!_n, - G!!iantiitative correspondence between the iin vi.vo and': in vitro activity of teratogenic agents - CA/i_?9'~6/17JS52F' - Proc. Natl. Acadl. Sci. U'., S'. A., VOL 7'97, ISS 6, 19u2„2CyS/-6~~3 J tT? :`i"U F'N I;', r-;iJA I L SI, - EMI!Cr''ci2:%OC1=3i•=I Sr -- ECOTCXI'CCL ENVIRON SAF; 6i:149-1c6.,,l.98':'' LA - Eh,G,~ HE'' EM I C./[7r;t=1L SEE g CA 97--2^41 - ENG - CBAC: CCFYF'IiGHT:: CHEM ABS ADDENDUM Sevcnty-, our teratogen i c anc. 28 nont_eratogeni'c agents were testfeci in a tiievpllopedl in vitro teratogen assay. The asSay i den+ i f i e d i:~-r atogens by thei r ability to i:nhibit attachment of a::acites tumor cells to plastic sur-f aces coated' wi th concariaval i n A. There was a quall. agreement between in vivo animall data and'n in vitro activi'ty for 81 of' 102 agents (79%). G!urantt. anal. showed ea highly significant correlation coeff. of 0.69 between thc inhibitory in vitro dose and the lowest reported teratogenic dose for 5'4 of 60 inhibitory teratogens. The doses analyzed rta:nged over 5 orders of magnitude. These resul ts were i.nterE:,rGted to, mean that attachment inhibition, in concert with other, complementary, in vitr-o assay systems can beco~~e a`~_e-~ut1 method for the assessment. of thetenratogeni _ poteniti al'i of envi. ronmental agents.
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AD' TI 5I So AL ~DUU=-1-k:NE; " CA E;t1ERSON E1.3 Pa I C H I NSr hd DD Dep. nad'iation, t? 21 1 51. Therapy, Harvard Med. Cch., 50 Binney E,..t., L;oston, Quantitative correspondence acti'vity ~:af tera.togeni~c - HEE'F'/C?1101f .T0 between ag,ents. h e +_'e i n' vYVO, and' i n vitro - E'}TtOC NATL ACA'I)' SCI U , S , A; 79 (-C.~) . 198:'. 1:c_)56-Y 'aF0',., - HEEP CQF'Yr'IGH T e BIQL AE+&. Teratogenic (74) and '3 nonteratogeriic agents were,tested in a recently d'eve1oped inn vitro teratogen assay system. The assay identifies teratogens their ability to,inhibit attachment of ascites tumor cell'.s to plastic surfaces coated with concanavalin, A. There is a by qualitative agreement between in vivol animal data _tnd in vitro activity for 81 of the 102 agents (79%)!. n4!enti;tt-itive analysis shows a highly significant r=0.f;9' between the inhibitor-y in vit~~~to dose and the lowest reported teratogeniic dose for 54 of thF 60 inhibitory teratogens. The doses analyzed ranged over 5 ' order=a of magniitude. Attachment inhibition, in concert with other,, complementary, in vitro assay systems can becorrie auseful method for theassessment of the, teE•-atogenic potential of environmental' ag,ents.
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1 AU -- 8lwensson ^'A TI - Propylene glycosi S'I - CI8/84/011298 SO - ArbetarsE:;ydd sstyrel sen', F'ub lli l::at i onsservi ce,j ( e4 ~1 171 84 8o1 na, Sweden, 1198:?'. ?8p. 113 ref. Bibl. Slwe Literature sur?vey to serve as a basis for determination of' exposure limits: metabolism, to:;'icity,, organ effects, other effects. F'ropylene •g,lycol has lowito:ricity; high doses have been given to animals in long--term es:periments without negative ef'f ects. Kld stud'i es that can be used to deter mi ne a hyg i en i c standar d are avai.llable. There is no evidence that inhalation of air saturated with propylene glycol has any deleterious effects'. \ 2 AU AU - M i1 ler- RR - H~2rmann EA AU - Young JT AU - Landry TD AU - C a 1 h ou n LL AD TI - To:<i col . Res. Lab., Dow Chem. U. S.A. , Ethylene glycol monomethyl ether and Mid prop land ylene glycol monomethyl ether: metabolism, disposition, and to:•i'1'Clty' st'udles subc hronie inhalation S1 -- CA/102/019c~=,45n SO - EHF`, Environ. Fiealth F'erspect.; VOL 57,, 1984,^..•.:_*-9 LA - EhaG •AB - CBAC COPYRIGHT: CHEM ABS Stiort--term and subchronic vapor- inhalation studies in rats and rabbits showed t'hat'there are pronounced differences in the toxicol. properties of ethylene glycol monometl-ry]: ether f'EGM1=) [1Icj9-06r-4] and propylene g'lycol monomethyl ether (1FGI"IE) [ 1= ~--67 8] . Overe:,posur e to EcMlE resulted in adverse ef-F'ects on testes, bone marrow and lymphoid tissues in, lab. animals. PGME does not affec t these tis'sues,, and instead, overexposure to PGME was assocd'. with increases in liver wt. and central nervous system ddpre,ssion. EGfIE iis primarily o:;idlized to methoxyacetic acild [625-45'-6] in male rats, whereas PGME apparently undergoes O-demethylati:on to propylene glycol. [57'-5,°i-6]I. Since methoxyacetic acid has been shown to have ttie sarrte sper_trum of 1o:,icity as f=rME' in rrralle rats, the obsdl, di f'f'er-ences in the t o;t ilcol . proper t i es of EGME and' F'GME are thought to be due to the -fact that the 2 m:~teria.ls are biotransformed vila di-fferent routes to different types of niF?tabol i tes.
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#i _,.. ..... T } .il f'.'r ..i\ r;L rc, !;r~g, j T r'ri II -- I_-a:.i h 0 L tn i_!' G'. _. E-t- I G:'t_ ~11 T <i,ccnl ., RF:s-. '~,ai:)., , Dow: Chem. }'_~`-;f„ , I'1iid?'and T'l _ Propylene gllycol monomethyl ether acetate (F'8ME'A) metabolism, dispo:i1 tl on',, and short-term vapor l nf + l at 1 o1Tt' to:; l c i ty studies C_- I C F, -. r~~-:.--c. cc U -- ': 1 :~,1 ~~~~,. ,. ,:~4J _:i_j' - T c~::icc~l . Ar,pl . F'h~A:rma_ol . ~ ',?~11L ;'°~ I--^_C' - , 1~i'84,,5~1-~:c_i LA ENG AHt' -- CF,AC CL1(F'v'f'~'IGHT: CHEM'' ADS Mail.e ir ats were giuen a singlie oral dose of .app~~~;.. 8'. 7 mmol / k:g o f 1-- ]: 4C---l a:bcl ed F'GMEA E 1<]`c3-6 ;-6] or exposed to 3000 ppm [1-14C]F`GME~-=A -for S h. After dosing, expired > air, excreta, and's tissc:tes were a.na:lyzed for 14C activity, and metaboliites, in urine were isolated and identified. Appro:r. 64% t of ti-.e administered 14r' activity was elimi'na'ted, as 1'.4ICU:' andl .appr-'c:.^4i: was e;;•creteU' in urine !-41th].n 48 h after a single orctl' do•ae' o7F raad'.ir-1labeled F'GM'EA. Sif-iia,!.,,r? yr, S?7: t•ras eliminatt_d as 14CO^ and'' 2.6% was: excreted in, urine within 48 h after the inhalation exposure. Propylene glycol C'57'-55-6], propyiiene glycol monome:thyl ether (1='8ME) 11:2c;-67'-8], and'i the PGME sulfate [85684-22-63 and'; F=`G1Y1E' g,lucuronidP C8`,68423-7] were iidentifi'ed as urinary metaboli'.tvs after oral' dosingl,, as well as: after i'nhaIation exposure to Fi:ME A. The.' urinary metabolite pro-rile and disposition o:-f L14C7R'Ct~~IEA were n:~s+•rly :identica'1 to reaultss pr-evi ously obtai nedi with r GME„ i nd i cat i ng that F'6MEA, i s r api d1 y and extensively hydrolyzed to F-'OM1= in vivo. A short-term vapor inhalation toxicity study in which male and female rats and mi,ce were exposed to c=1,, T0{i,, 1t_fCi;:),,, or :iJ<ici ppm PBMEA, confirmed that there were no substantial raifferi=-nces in the systemic effects of F'8M'EA as compared to f'CI1E. Vlowever, histopathol., examn. diid' reveal c han'gE~.~s i rn the ol factor--y por- t i. ons of the nasal mucosa~ of rats: and mice exposed to F'rtiEA, whach may be rei!atedi to HOAc resul tiing fr orn t-rydrol ysi s o-f F'6f1EY), i n the nasal epi thel' iurri.
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F. j_j ...... -: : . ; . hijt. f-i i_ti _. T l ~-: _ ...T r,C7 ., ~tTo;ic c~ lR Ee s c? _.r- c,~r I:_.n~'i e r-~tr T1 C'r__ign;, _e.i_ a--uction and operation ot a. i.nh--l:?-ti'on. D 0 •_U C-~_ °=V ..?.tE~ ti! SI 'r,;:~i!i.~~T -+-r ,-~c~-=y_~:;~,`•:~~~ I_,N1.~'l(i: 1S '.. c _•. -_ ,~ry~ + ; fn . f1 ~pp l . T_ cr1 . ~.r °~1L y', ISE 1, 1'~'ia - _ r,~,, ~ i ~ , _ , LA - ENi= f=1E-, -- L-III Hi~~: CnF'YF.`IGHT'e CHEM ABS Art inhalation exposure system was de_innNe',I' from an, .?il,l g,1ass aquarium with a vo1. of =:91 L. A top, 'or •the c1hafnber- was fabricated from a:cr ul ic nlastic and Teflon wi tlti, an i nl et , out';l et , 5 sampl i'no. poi~~i, s,, a:nd hand'l es, Si_rpp,1 y ai e to the chamber was charcoal and HEPA f i l tet-ed. Ai r f l: ow through the chamber is horizontal and' range' from 50 to 20t=? L/min. Air f l ow i s measured by a g I ass tube rotameter and regul ated by PVC va 1 ves:., C'hamber aii r was HEE`A and~ chareoN.l -f i I tered' pr i or to e:aha,_rs'ting it to ambient air. The operating characteristics of thi sexposur~-e system were assesseci' usinq test atmospheres: of HCHC CI,i n--hn:<,ane [110-54 371, aridi an aerosol of propylenEc gI vcol n57'-55-61. Expressed as percent of a central sampling point, the chamber concns. of HCHO, C1 r'.nd n-ne;:_ane was, 91'°6->:0`.73'/°, No differences in chamber distribution were noted at ;8 or 1••G L/mini (correspondiing to 12 and '20 chamber vo1s./h). For propyl ene gil ycol ,, the mass medi an aE?rod'ynarf,i c di am. at a chamber %~?:1 r" $• I ow o`i' 79 L/mi n vc'~-r."LCed -`rirOIl1l i.- l to 1.63 . iii111i. m. Gilmiiar- results were found at 1-'•:r=r L/mirrs- During mass sampling al cone.n. pradient wa-s founJ fromm the inlet to the outlet of the chamber and rangedi from 5 i,to 99% of the i rrl et concn. Thi c:%: inh4alation e;;:posr_ire system is': vcry sui:ta-ble for acute or subacut~- inhaiation studies of gases or vapors but, is orily satisfactor,v ~ -For a>?r-o,ol sunddr eertai n operat i n'g condi t i' ons. r1U - Gtapt a 1"I AU AD - Chatter i e'•? T - Pharrmacol. [';>=s,. S'ee.,, Eiept., of Phanm.,, _•-dMvpur Univ., Calcutta 700 i>;='2, Ini±'i _:- TI -- Effects nf citrinin on cannabi=: (Gan_i.=~) =mo~-:e ir+haled! mice GI -- IPA/F_ r~:i SG, - Indiari, J. i-iospi. rha-r-m., VuL 13 IW6 Nov--Dec 19'8)1, E2ti0-s!s)2;, (REF LA _ f). E'NG AB IPA [;C.F",'RI[;HTe r-+G{~°~F" The effects of citrinin,, a possible pillant r-ontaminant, an the drowsiness induced by cann_sbiis smoking viere Jtud'i ed i n mi cc-.G'ar i ous dosages of' propyllene gllyeo-1 _al one <<nd iitrini:n dz s:,~-~_lv•_=a iin propylene g,Lyco1 were aciministered if~=' bE~-tore tilcc ~TiI,± -? t.+?et->-''3 e)C'posed ' to the srllo(~r:? -if a -c:,fln<_bl,£-i f rpar i te. Induction of sleep, m~~rtalit; rrates arrdi fr-c_aaUn:em~:•y o-r lUrl:nr3/_i iin were al l! :Lincr'F•,aselCj wi'1_h 1'n_r= t-~s7-nQ doses of tila u-ehlcl f-: and : evefv tTi=!r~ so with tihe veh]-cle ' with ri t rr'lri/17-
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)! haF'-r~Y~::.ER 1.., .I ,_~~ ~ _ L NC1E!•~, I. T'I - THE hIEURt'~~_+ Tr,::ICITY OF (,1._C:3I•-I0L"3 Si I F-lEEP!82,/ 124?,_ ;i, PF=L7CEED'Ih..l.l__ ; Oi- }..1E CONFERENCE ON THE lNl<.;UF.:C7O)`ICI'TY OF C1F.CANIC. CEJL_VLId TS AfraD iyCtt,rLANII DE. 9 i:A1_E IGHs 1•'•~. C. „?. j'=iij, •.7U!'dE 262:' S 1981. 'PdE:JRQE;E!-iA'!1 TQkI'CL+L. T_FiATOLq =(4). , 1^0:I. (•:ECD,. 1''9C..t). 4=5-4:'b. LA -- ENG ' AL! - HEEP CCE'Yn I G'F,iT , L: I QL i ir:C,. HU["fAhd A1`d',Il`1AL F-ETAL F'ATHOLGCY' h'IEr'lE'•Fi~ ANE I t'aHl`aLAT I Oh! C:CCUF-'AT I OIXI aL HEALTH
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SEARCH FORMULATION F=;ErlN' , 1dTNG AT ' ~u 1 11:G-1'4-8 AND GREATER THAN !:.,-.;07' (EP9') ) -- '_.7 i'(1STINGS '=.Ef ;;CHI FORM1!LATIO11. '_'.,Eu IN!`aING' AT ' r 2 (~57-55-6 AND GREATER THAN-8'1 1 c-7 ( E;1) ) -- 621 POST I hdGS SEA.CN FOF'ML{LAT I 0N E'EG I I'dNI hk!r AT C S ' (ZS 2 AND TOX I C (SN )) ---- 20 `="nST I h:lE;S SEARCH FORMIllLAT I Ohd' L-sEG I h{hllI NG AT SS 4% (SS 3 AND NOT FOR ( LA )) -- 1 2 F'OST I IVGB SEAhCi-i' FORh1ULAT I'Ohl F{EG I1'dNI'NG AT S`_i .°i : (SS ^' AND MUTATImI'di (SN) ) -- 7 F'OSTIpJGS SEARCH FORMULATION BEGINNING AT SS 6: (;SS L AhUD NOT ,-c,S a), -- 7 c'OS TINGS SEARCI-i' FOF;MULATIOhP BEGIPJN'ING AT `=S 7: (SS', 6 AND' NOT FOF; (LA) ) -- 6 POSTINGS SEAFiCH' FORMULATION H{EGI'NlVI'N&AT SS S:. (SS 2 AND TERATO (SN) ) -- 5 POSTINGS SEARCH F 0~'~NULAT I ON L-'EG I h3hJ I NG AT S S 9 Y (SS 0 AND NOT FOR (LA) ) -- 5~F'O ST'INGS SEARCH FO RM'ULAT I0N rtEG I NNI I`1G, AT SS 10' : ( Su• 2 AND ALL I!uHAL: ), -- 6 F'OSl'I I'UGS, ha0SiJBMEADINGS A+•F'LIED TO ANY SEAFiC1-i STATEMENT.
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CAS ONLINE@ The CA file contains records for the documents coverediin Chemical Abstracts for the time period 1967-present. Chemical Abstracts covers journals, patents,, technical reports, books,,conference proceedings, and'd'issertations from all areas of chemistry and chemical engineering, worldwide. The CA file contains over 6 million records, and is updated'biweekly with an additional 14,,000-18',000 citations. The document records in this file contain bibliographic and indexing,information: fo~r searching. Over(bU%,of therecordsalsocontaiin abstracts for display. The next two~ pages of this pamphlet give inf ormatiion on the search and' display fields in the CA file, the formats which are available for online DIlSPLAY an& offliine PRINT of records, and'~ show samples of journal and patent records.
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ANSWER' 1 r. AN CA103(5):33308e TI: Decomposition reactions of (hydroxyalkyI)nitrosoureas and rel'~at'ed compounds: possible relationship to carcinogenicity AU Singer, Sandra S. CS Frederick Cancer Res. Facil., NCI LO Frederick,,MD,217Q1„ USA SO J'. Med. Chem., 28(8), 1s;488-93' SC 4-6 (To;<icoiogy) DT J CO JMCMAR, IS 0022-2623 FY 1985 ' LA Eng AB ' Decompn., reactions of'. the title compds., 1-(2'-hydroxyethyl)'-•1-nitrosourea CL3743-r77-^cl, 1-(2-hydroxypropyd)-1-nitrosourea C'71752-69-77, 3-niltrosooxazolild-2-one (138347-74'-97, and 5-methyl-3-nitrosooxazolid-2-one C79624-33-2'], were studied'in aq, buffers at physioi, pH to det, the pattern of'p,roduct formation that might be related to carci,nogenesi's. Related dial,k:ylnitrosoureas were also subjected to decompns. in buffer followed by product anal. Tihe products predicted by 1'iterature mechani,sms,for these decompns, were the compds. formed- The tests compd5, were,diissol,vedlat pH 6.4-7'.,4' in 0;.067' or CL1M phosphate buffer at 37.,degree, employing', several methods of ana:l. At the above pH,, epoxides,were stable reaction products; however, in the presence of hepatocytes., most epoo;ides were converted to glycols. The results reveal! no clear-cut pattern of" product formation that could be directly related to carcinogenesis. Some of'the products were highly active compds. which are carcinogens in their own right, and they may be,responsibSe for some or alil, of' the carcinogenic activity of' the test compds. if' they are formed by decompn. of the test compds. at the:target org«n. KW carcinogenicity al'kyrlhydroxyurea nitrosoo..azolidone decompn IT Degradation (of (hydroxyal'kyL)nitrosoureas and related compds., carcinogenicity'in relation to) IT 75-07-0, biological studies 75-21--8, bioloqical studi'es, 107-21-1, bi,ologicali studies (as (hydroxyethyl)nitrosourea decompn.,product,, carcinogenilcity in IT IT' I T relation to) 57-55-6, biologi,cal, studiies, 67-64-1, biological studiies 75-56-9, biological studies 123--38-6, biological studies ('as (hydroxypropyl)nitrosourea decompn, product, carcinogenicity ~, in relation to) ~ 107 Ci7-3, biologrcall studies ~ (as chloroethyIurea deriv. decompn.product, car-cinogenici,ty in ~. relation to) ~ 7U8E-r ii_)-y ,,7175 8._-2I W (as deuterohydro<yethylurea deriv. decompn.product, w carcinogenicity in rella.tion to) N , 1
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IT' 1iQ8-32-7 (as metPoylnitrosooxaeoliidbne decompn, product„ carcinogeniciity relation to)' in IT 96-4I9-1 (as nitrosooxazolidone decompn, product, carcinogenicity in ' IT relation to) 154-9:s-8: 1"q10-47 4 1,'s743-U7-2' 38347-74-9 59960-30-4 60784-46-5 66929-45-1 71752-69-7 75014-24-3 77081 '<1-2 79624-33+-2 96806-34-7 96806-35-81 (decompn, of, carcinogenicity iin relation to),
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ANSIJER: 2 I AN', CA1'O? (3) 1 :i 18258v TI An evaluation of' the utility of four in vitro short term tests for predictingithe cytotoxiicity of individual compounds derived from tobacco smoke AU Curvall„ Margareta;: Enzell, Curt,R'.; Pettersson, Bertil; CS Res., Dep.,; Swed. Tobacco Co. LO Stockholm S-104 62, Swed. SO Cell' Biol. Tonilcoi., 1(1), 17-,-93SC 4-8 (Toxicology) DT J, CO CBTOE2 IS 0742-2091 PY 1984 LA Eng AB Bio1. activity of 305 compds. (12 groups according to main functionality) was compared'.by 4 in vitro tests, i.e., the cel'l l growth ofl Ascites sarcoma BP 8 cells, the oxidative metab. of isolated brown~fat celil's from adult hamsters,, the membrane damage of human diploid embryonic lung fibroblasts, and the ciliary activity of'f embryo chicken trachea., The results are tabulated. The phenolss constitute the most active group, followed by aldehydes and aScs. The least active,are the furans/thiophenes andlthe esters. Among the'e phenolls, the alk.ylphenols are highly acti've. To f'i,nd whether the toxicity of some,ofl these compds., belonging to di~fferent groups might be due primaril,y'to a common subunit„ 45 descriptors were selected~ which included the 12 functionalities. The computer-assistedl mat'chiingiof these and any combination of them agai,nst,the mean activi~tu showed the most toxic singl'e descriptor group to be terpenoids followed by indoles and naphthallenes; the most toxic 2'-descriptor group~was .al'pha.,,.beta.-unsatd, carbonyls, followed by n-alkyl a1cs.„ aldehydes, and acids. Intersystem similarities and differences, using a high-medium-low scale, i,ndicatedlthat all the 4 test systems give the same results for 35% of the compds. KW chem cytoto:<i~city predictkon;~ tobacco smoke chem cytotoxicity IT Trachea (ciliary activity of, cytoto;ai~csity prediction f'.or chem. _ompd<s. of tobacco smoke from in vitro tests i:n relation to) IT I'TI I',T'~ IT Tobacco smokee andlsmoking (components of, toxicity of„ cytoto;:i'ci'ty predi~ction from in vitro tests iln relatiorn to) Molecular structure-biological actiwity relationship. (of compds, of tobacco smoke, r_ytotoxicity'prediction from in vitr o tests' in relation to) Cell membrane (of' lung fibroblast, cy-crato:,i'city prediction for chem. tobacco smoke from in vitroi tests in relation to). cempds, oi Anhydr i des OD Alcohols, biol'ogical studies -.1 , Aldehydes, biological st!!diies ~ Amines, biological studies ~ Aromatic hydrocarbons, hiollos,ical studies ~ ~ Carhoxylic acids, biological studies r~ Esters, biological studies ~ ~
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Ethers, biological studies K.etones, biological studi'es Fhenols, biological studies Terpenes andlTerpenoids, biologi,cal, studies (toxkeity of, of' tobacco smoke, cytotoxicity predictiion from in, vitro tests in relation to) IT Sarcoma(asciltes, cell growth inhibition of, cytotoxicity prediction for chem. compds., of tobacco smoke from in vi'tro test in relation to) LT Adipose tissue, metaboliism. (brown, adipocyte, oxidative metab, by,, cytotoxocity predi'ctioni for chem, compds., of tobacco smoke from,.in vitro tests in rel'ation to) IIT Toxicity - (cyto-, of chem. compds., of tobacco smoke„ predicti'on:of', in vitro tests in relation to)' IiT Heterocyclic compounds (nitrogen, toxicity of, of tobacco smoke, cytotoxicity prediction from in vitro~ tests in, relationito). LT 50-32-8, biological studies 51-17-2 54-11-& 56-55-3 57-55-6, biological studies 59-67-6, biological studies 60-112-8 62-53-3, biological studies 64-17-5, biological studies 64-18-6, bioIogacal, studiies 64 19-7, biologiical studies 65-85-0, biological studies 66-25-1 67-47-0 67-56r1,, biological studies 67-63-0, biologi'.cal studies 67-64-1, biological studies 71-4y-2',, biollogical studies 75-05-8, biological studies 78-81-9 78-82-0 78-84-2 78-85-3 78 93-3„ bioIogical studies 78-94-4, biological studies 80-56-8 83-32-9 83.-33-0: 83-34-1 84'-66-2' 84-74-2I 85-01 8, biologicaL studies 85'-44'-9' 86-28-2 86-53-3 86-74-81 87-51-4, biological studies 87-59-2', 87-62-7' 87-66-1 88+-05-1 89-81I-6 90-00-6 9t?-02-8', biological studies 9is-05r1, 90-12'-0 90-15-3 91i-1'O-1 91-2tD:-3, biological studies, 91-22-5,, biological studies 91i-5W-4 91i-57-6 91-59=8I 91-64-5 93-04'-9' 93-18+-5 95-13-6 95-20-5 95-48-7, biological studies 95'-53-4„ biological studies 95-65-8 95r78-3 95-87-4 96-17-3 97-53-U 97-54-1i. 98-00, O 98-82-8 98-86-t, biological studies 98-92-0 99-49-0 99--93'-4 100-21-0, biologiical studies 100-41'-4',, biological studies 10O-42'-5„ biological studiies 1i00-46--9„ biological studies 100-47-0,, bioLogical, studies 100-51-6, bioliogir-aI, studies 1i00-52- 7', biological studies, li1o-5.4-9 100-6'6-3, biologicaii studies ~ 10O-83-4' liii0-84-5' 1oi1',-81-5 101-E34'-8 1,~7 -41 103-65-1 ~ 1V:3-69-5' 1103r73-i 104 53-c( 104-55-2 1,iD4-35-8! 1t~!4-87-0 ~ 1i)4-97-8 ll05-5.:;-3 105-67-9 100-21-s3 106-24-1 . 106-41-T', ~ biiol'ogical studies 106-44-5, biological studies 1V6-49-V,, ~ biological studies 107 02'-8:, biollogical studies 10 il!-9' lOD-1i2-0 1ICi7-1:3-ll„ biological studies 1107-87-9' 108 OS-4, ~ biological studies 108 _•8-3, biological studi os 103 Z9-4„ Cj biological studies 108-4!4'-1,, biological studies ?0,`3-46-3.,. UT bimlogical studies 108--48-5 DiiO -5ii-9 108-6?'-G. bioloqi=al studies li_8--68-9 L08-75T-S, 108'-88-_„ bioloaical studins, Li 10g-94"I, biological studies i02 95'-2, bii-Dlo3iuc:1 studies _ 109-Ci6-8 lnr9-08-ii 109-7-T•-9, biological }bldies 1'ir9-74-=! 1cf9-96-6 109--97-7 1U9-9=7-'9', biological studies 1 i0-i ii-9 110i-110-9D, derivs. lS ? 02 1 110. 0.2-1D, deriv_;. il0 110-/i2-Z bioliogical stud'ies L11<-i--86, 1, bioloaicai 4
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sturdies, 110-89-4, biological studies, 110-9Z;-<j 1,11'-26-2 111-27-3,, bi'~ological studies 111-61 5 111-71-7' 11,1-87-5, biological studies 1'12-05-0 112-7.0-1 1'12-31'-2' 112-44-7 112-54~9 114-•373-0 11'6-26-7' 117-84-0 119-64-2 12Cy-12-7, biologi~cai studies 120-1419 120-51-4 120-72-9, bio.ogi'cal studies 120:-80-9, biological' studies 120-92-3 121-33-5' 121-71-1 122-39-4i, biological studies 122-78-1 123-07--9 123-178-0: 123-11-5, bioliogical studies 123-1'5~-9 123-;1-9, biological studies 123-38-6, biological studies 123-72-8i 12'3-75-1, biological studies 124-07-2, biological studi'es 124-12- 9 1!24-11-{=t 124-19-6 126-98-7 127-91--3: 128-'7-0, bi':ologiica'L studies 129-00-0, biologicali studies 1~1--16-8 132'-64-9' 134-32-7 1._5-19-1,, biological studies 1,=8-86-a 139-85-5 140-111-4 14Cf-29'-4 141-10-6 142-62-1 , bi'ologi~cal studies 143-08-8 150-19-6 1'50-76'-5, 1911-07-1 198-55-0 206-44-0 208-96-8 213-46-7 21'8i01-9' 244-63--3 271-89-6. 275-51-4 290-37-9 334-48-5 367-47-51 4311-03-8 432-25-7 486-25-9 486-56-6 486-84-0 487-19-4 487-68-3 4'87-89-8I 468-1i7-:, 490-79-9 492-27-3' 494-52-0 494-97-3 495-40-9 496-1'1-7' 496-72-0 4'96-78-6: 499-74-1 500-22-1 505-57-7' 526-75-0 527-60-6 529-1'9-1 529-20-4 5Z0-57-4 536-74-.'';: 536-78-7' 571-58-4 576-26-1, 578-54-1 58'2-24-1 589-16r2' 591-22-0 592-43-8 592-4'6r1 600-14-6 603-76-9 613-46-7 614-96-0 620--02-0 620-17-7 620-22-4 6G:r--23-5 621-82-9', bi,ologi:cal' studies 623-36-9 625-30-9 625-33-2 (toxicity of, of' tobacco smoke, vitro tests in relation to) cytotoxicity prediction from in IT 625-86-5 628+-7?-9 629-08-3 629-76-5 67,53-19-3 6-14-;6-6 645-59-0 697-82-5 698}711-5I 771-51-7 814-78Y81 823-40-5 374F63-5 875r'0-9 875-79-6 928-68-7 93rf-68-7' 9,-1',67-5 1002-84-2 1004-66-6 10317 32-5 11196-79-81 1462-84-6 1490-04-6 1570--4'8-5 1604-28'-0 1971-46-6 2016-57-1 2138-48-9 2305-211-7 24i_i8-37-9 257L-52-0 31i89-12-6 4028-66-4 417<!-'0-3' 4360-47-8 4427-56-9' 4602-84-0 5724-56-1 5779-94~2 6575-1'-9' 8000-41-7 8013-90-9 10299-63-5 1'37~-T•~0-09-1, 15764-1 6-6: 15877-57-3' 20469-6i-81 21296--92-4 21789 36-6 2'4l.'2-35-1 228B4-95'-3 25Z09-65-? 27505-78-8 34136-57-7 Z41=6*-59-9' 8tJ466-v 4-8 (toxicity of',, of'. tobacco smoi:e, cytotoxicity prediction from irr vitro tests in relation to) 5
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ANSWER 3. Alvb CASC12(23)',:A99C185j TI Hypoli,pidemic effect of propame-1,,2-diol on the morphology of rat erythroaytes, Ahluwal'ia, Pushpa; Amma, M. K. P'. Hilochem. Dep., Panjiab Univ. Chandigarh, Indi,a Res. Bull. Panjab Univ., Sci., 35(.3-4), 157-9 4-3' (Toxicology) J RBJUAT I S' C15.55-76' 1 PY 198:41 LA Eng AE+ In rats given 284 mu.L of'propanerl,2-di,o1 Q57-55-6]' in water for 30 days:, the,levels of total lipids, cholesterod, C57-88-5],, andi phospholipids of' erythrocyte membranes were significantly decreased. The ce17 s maintained a normal shape buti were spurred. Their outer membrane appeared under the eIectron microscope as very rough, having crenati'ons and deformations'. Apparently, alterations in the compn. ofl the membrane liipids changes the cellular morphol., which is very essential for the:normal metabol!ic function of'erythrocytes. KW propanediol toxicity erythrocyte; membrane erythrocyte l'ipid propanediol. IT Phospholipids Lipids, biol'ogicaS studies (of erythrocyte membraney propanedi,ol, effect on, cell'ular morphol. in relation to) IT Cell membrane (of erythrocyte, lipids ofl„ propanediol effect on, cellular morphol, in relation to). IT Erythrocyte (propanediol toxicity toy membrane liipids in rel'ation to) IT 57-88-5y biological studies (of erythrocyte membrane, propanediol, effect on, celliular morphol. in re3ationito) IiT 57-55-6, biologicaU studies (toxicity of, to erythrocyte:,, membrane,li.pids,in relation to) AU CS LO SO SC DT CO
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R ANSWER 4 AN CA102(3):19302W TI' Developmental toxicity'and structure/activity correlates of gl~ycols, and glycol ethers AU Jbhnson, E. Marsha,l'I; Gabell„ Bradley E., G.g Larson, John CS Daniel @augh,Inst., Jefferson Med. Coll. LO Fhiladelphi,a„ F'A 19i'07, USA SO EHP, Environ., Health F'erspect. „ 57, 135-9 SC 4-6 (Toxicology) DT J CO EVHF'AZIS: 0091-6765 PY, 19841 LA, Eng AB Of 14 glyco7s andlgllycol ethers tested for embryo and adult toxicity in Hydra:attenata, diethylene glycol C11'1-46-67, ethylene glycol monomethyl ether monoacetate G1'1'D-49-6]„ ethylene glycoi monoethyll ether monoacetate ai11-1'5-9], and ethylene gaycoll diiacetate t11'1-55-7] were~equall,y toxic to adLnlts and embryos (the indiWiduall compds, had differing toxiciities). Ethylene glycol C107-21-1] had the greatest embryotoxicity relative to adult toxicity. No obvious structur'e-activity'relations,between these compds. and devel,opmentall toxicity were obsd., in this test system. KW: development toxici~ty gl'ycol ether Hydra IT Glycols, biological studies (developmental toxicity of', in Hydra attenata assay, structure in relation to) IT Senescence and Senility' (glycol ethers and glycolls toxicity in rel'ationito,, in Hydra attenata assa.y) . IT Hydra attenuata~ (glycol ethers and gaycoiis toxicity to+ development in relatianito: ) IT Embryo (glycol ethers and glycol's toxicity to, in,Hydr-a attenata assay), IT Toxici~ty (of glycol ethers and glycols, in Hydra attenata assay, development in relation to) IT Molecular structure-bioloaical activity rel'ationshilp (toxic„ of' glycol ethers andl gllycol s„ in Hydra attenata assay, development in rel!ation to) IT 57-55-6, biological studies 147-21-1, bioloqicaI studies 1107-4I1-5 109-86r4 110-49-6 1110-8G'-5 1111--15-9 114-4b-6, bilologiaall studies 11I1-::,5-7 1''11-76-:.' 111-77-3 111-90-0 11'2-73'-2' 122-99-6 (developmental tanicity of,, in fhydra attervata assay, structure in relation to)
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ANSWER 5 AN CA102(3):19045q `/ TI Ethylene glycol monomethyl ether and propyd'ene gaycol monomethyl, ether: metabolism, disposition;, and subchronic inhalation toxi,cityy studies AU Miller, koliand F'.; Hermann, Emiile,A.; Young, John T.; Land'ry,, Timothy D.;: CaShouny Linda L. CS Toxicol. Res. Lab., Dow Chem. U.S.A. LO Midland, MI 48640, USA SO EHF, Environ. Health Perspect., 57, 2=.3.-9' SC 4-3I (ToxicologyJ' DT J CO EVHPAZ; I S 0091' 6765 PY 1984 LA Eng',. AB Short-term and subchronic vapor' inhalation studies in rats and rabbits showed that there are pronounced differences iin the toxicol, properties of ethylene glycol monomethyl ether (EGME) C109-86-4]1and propylene gaycoii monomethyl ether (PGME) C1320-67-8]. Overexposure to EGME resulted in adverse effects on testes, bone marrow and lymphoid tissues in l'a6, animal's. PGME does not affect thesee tissues, and instead, overexposure to F'GME was assoad. with i~ncreases in liver wt., and central nervous system depression. EGME is primarily oxidi,zedlto methoxyacetic acid C~625-45-6] in male rats, whereas PGME apparently undergoes 0-demethylation to propylene glyaoli Ei57-55-6]. Since methoxyaceti,c acid has been shown to have the,same spectrum of toxicity as EGME in male rats,,the obsd. differences in the toxi,col., properties of EGME and it'GME are thought to be due to the fact that the 2 materials are biotransformed via different routes to different types of'metabolites. KW ethylene glycol monomethyl' ether toxicity; propylene glycol monomethyl, ether metab;, ether ethylene propylene glycol,toxicity IT 625-45-6 (as ethylene glycol monomethyl ether metaboI,ite,, toxicity in relati'loni to) I'T 57-55-6, biicnlogi~caS studies (as propylene glycol' monomethyl ether metabolite, to::icity in relati'loni to) IT 109-86-4 1.;2C7-67-8 (metab, and toiici,ty of) ~ ~ ~. ~ ~. f6
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ta G. ANSWER 6 AN T I', AU CS'. LO SO'. SC. Sx DT CO i IS~ Py LA. AB CA 1 C11( 23) : 2 i_r9264 n Pri,mary mut'agenicity screening Japan Ishidate, M., Jr.; Sofuni, T.; Sawad&, M. g, Matsuok.a, A. Biol. Saf. Res. Cent., NatI. Tokyo 158, Food Chem., 17-5 (Food 4 J FCTAD7 0278-6915 19841 Eng Japan of food additives',currently'used in Yoshikawa, K. ; Hayashi'„ M. g, Nohmi,, T. g Inst. Hyg,., Sti'~. Toii,col-, 22(8),,, 62v-a6 and Feed Chemistry) Salmonella/Microsome tests (Ames tests), and chromosomal: aberration tests in vitro using a Chinese hamster fibroblast celli liine were carried out on.19U' synthetic food additives and 52'food additilves derived from'.natural sources, all of which are currentl,y'used in Japan. Fourteen out of 20n1testedlin the'Ames_assay showed pos, effects and 54 out of'242'were pos. in the chromosome t'est. Three additives (erythorbic acidl C89-65-6], C1i02„ and beet red) were pos. only'in the,Ames test, although their mutagenic potentials were relati'~veiy weak, while 43 additives were pos. only in the chromosome test., Eleven additives, Ca(OC1)12, cinnamic aldehyde C104-55-2]i, L-cysteine.HC1 C52-89-1171, Food Green No. 3 (Fast Green FCFY C2a53-45-9], H202, KBrO3„ NaC102, NaOC1,, NaN02,, cacao pigment, and caramel, were pos. in both the Ames test and the chromosome test. The,usefulness of' such primary screeniingi tests combining 2 different genetic end-poiints, gene mutation and chromosomal aberration,, and some correlation between mutageniicity and car'ci'nogenicity of food additives are discussed, mutageniciity food additive IT IT IT IT IT IT IT screening Food (additives, mutagenicity screening of) Oils' (cinnamon barS::, mUtagenici'ty screeningi of ) Oi 1 s (clove, mutagenilaity screening ofY Oils ~. (coriander,, muitageni,ci'ty screening of')') Oils ~ (cumin, mutageniciity screeni~ng, o{i) ~ Fesin acids and Rosiniacids N (esters, food additives contg., muta.ge.nicity screeninq or') A le (rJ pp (ext., food additive,, mutageni'laity screening Coflfee Cola ('genus), (ext. , mutageniciity screeninq, o{i) IT, Anise of ) , 9
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IT IT IT IT' IT IT IT' IT IT IT IT IT' IT' IT' IT IT! IT Caramel (color Ceratonia sid,iqua ChSorophylils;, biological studies (food additive, mutagenicity screening of') . Oils (grapefruit, mutagenicity screeniingi of'3 Chlorophyl'lins (i~ron-sodiumi salt,, food additive, mutagenicity screening, of) Oils (lemon, mutagenicity screeningi ofl) Oils (liime, mutagenicity screeni,ng of) Oils (mustard, mutagenicity screening of) Oils (nutmeg „ mutagenicity screening of). Oils (onion, mutagenicity screeningi of;) Oils (orange „ mutagenicity screening of) Oils (peppermint, mutagenicity screeniingi of) Oils (perillia,, mutagenicity screening of) Chlorella Cocoa (pigment from, food additive, mutagenicity screening ofi) Beet (redl pigment from, food additive, mutagenicity screening of) Siloxanes and Sililcones, compounds ~ (resins „food additive, mutagenicity screening of) ~' Oils ~ (sage,, mutagenicity screening of)' ~ Polyphosphoric acids (sodium, food additive, mutagenicity screening of) (j . Oils ~ (spearmint, mutagenicity screening of) ~ Oils (thyme, mutagenicity screening of) I TI IWuc 1 eoti des, compounds (5i'-, sodiumisalt,, as food additive, mutageni'city screening of) IT 50-14-6 :rCi-24--5, biological studies 50-70-4, biological studies 5t7-8L'-7', biological studies 51r-c?._-6 54-12-6 5.6-4~i-6, bioliogical studies 56-81-5, biol'ogi.lcaT studies 56-81--SD, fatty acid esters 57-50.-1,D, fatty acidl esters 57-55-6, bioliogical, studies 57-55-6D, fatty acid ester 58:-Ci8-2, biological studies 58-56-u 58+-86-6, biological studies 59"67-6„ biological studies cT,-91-27„ tiiological' studies 64-19=7,, biological studies: G5-B.SrU,l biological studies 670:::-8' 67-64'-1„ bi;ological; studies 67-Q7-0 68-04-2 69-65r8 72-17-3 7^-L8-4, biiological studies 72-19-5, biological studies ,_ ----„ biological studies 7.~-_2-`= =,j biologicall studias 75r^1--8D, alk:ydi ether 77-22--9, bnological studies: 78-7Cr-6 8r)-68-2 81-07--2 E'-86-' 8."-e8--5' t57-08-5, biologicali studies 87-69=4„ bialogica,l 3t'urdies: 89-65rc 9U-8G-2 9-2-52=4„ biological studies 941-26-8 biological studies 1U;
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97-53-0 98-92-0' 100-51-6, biological studies 101-97-3 103-36- 6 104-55-2 104-67-6 1o5-17'-3 105-54-4 105-68'-Ci 106r24-1 106-27-4 iO6-321-1, 107-92-6, bi'ological studies 108-64-5, 110-15-6, biological studies 110-17-8, biological studies 110-44- 1 1i1f1Y45-2' 110-54-3, biol'ogacal studies 110-91i-8: 1112-31-2 119-36-8 123-92-2 140-03-4 biological 150-90-' 520-45-6 632-68-8 120-47=8 127-09'-3 141-78,6, studies 302-72'-7 526-9Fi-4 659-70-1, 121' 32-4 121-33-5 1211-79-9 123-86-4 128-4419 130 -40-5 137-08-6 137-40'-6 biological, studies 141-97-9 144'-55-81„ 1144-62-7, biotogical' studies 148-79-8 452-37-7 497-19=8I,, biological studies. 5'2-3'2-1 573-Q9=1 584-1t8-7' 617-48'-1 676-46-0 860-^2~-<:1: 868-114'-4 868-18-8 91'5-67-3, 11066-33-7 1185--57-5 1v93-63-1D,, potassium salt 1393-63-1D, sodium salts 19~4-21-Ci: 2111-75-3 2353-45-9 2611-82-7 2Ei67-891-2 2783-94'-ia 3081-61-6 3520-42-1 7567-69,-9' 3792-50-5 3i344-45-9' 4075-81-4 4191,-7ur5 4247-02-.'. 4320•-30-3 4418'-26-2 4691-65-0 5392-40-5 5550-12-9 5793-94-2I 63811-77-7 7235-40-7 7487-88-9„ biologi,cal studies 75r45-48-4' 7558-80-7 7632+-00-01 7585-39-9' 7631-90-5 7631--99"4„ biological studies 7681,-52-9' 7720-78r7 7722-84-1, biological studies 7727-54-0 7757-79-1, biological' studies 7757-83-7 7758+-01-2' 7758-16-9' 7790-53-6 7758'-1'9-2' 7778-54'--3 7786-30-3, biological studies 9GOq-91-3 9041-63'-2' 9001-73-4 9003-04-7 9003-20-7 9003-27-4 9004-32-4 9004-67-5 9005-37-2 9U05-a8-.31 90:32-U8-0 9050-04-8 9063r?8-1 9082-G}7-9' 1'0043-52-4, biological studies: 1<j043-67-1i 10049-04-4' 1h191-4'1-0 : 1«236-47= 111013-97-1 11103-57-4D, ratty aci,d ester in oil 1'21,25-02-9,, biological studies 12441i-09 7D,,fatt,y acid ester 1'3718-47-7, ' 1',5.=56-7U•-4 16177-21-2 16731-55-8 18299-48-4 18472-87-2' 24'634-61-5' 25013-16-5 25322-68-_D,, a11::y1 ether 263117--27-1 27214-00-2 283C)2-736-.°, 28633-45-6 30587-81-6 35660-60-7 39465-00-4 39479'-631-5 49720-05-0 50813-16-6 5o984-526 53241-1,5r9' 57817-89-7 60687-93-6 71'277-78,-6 71277-79-7 75602-64-1, 94238-00-3' (flood additive, mutagenil¢ity screening of) IT 52-89-1P (prepn. of) 11
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ANSWER 7 AN 6A 1'O 1( 23)I : 2D541p j TI pT, a,new system for the comparative classification of'toxicit'y AU Montoya-Cabrera „ Miguel Angel Dep. Toxi,col'., Hosp. F•ediztria M ex., Cac. Med. Mex., 12+_? (3),,: 101-7 J 1'984I Span AS An aliternati've to, LDS0 is proposed for expressing the toxicity ofl drugs,and other chem6 substances. The new parameter, pT, is defined as,-1ogiCT7,, where CTI is the-LD5p in g dividedlby mol. wt. OraL LD5r7 in rats were, obtained from literature for 1'09' chem. substances (including 36 drugs): and converted to pT50. The pT5U ranged flrom. 11.03.for acetone C67-64"27 to 5.54 for fluoroaetic acid Ci144-49-q]. Ten of 36 drugs and 20 of', 28 org. sol vents had pT5(? <2; whi, l e only 2 of 32 pesticides had pT5f,1 <.2.. KW toxicity comparative classiifi'cation IT Toxicity. (classification of, by pT values) IT Chemical,compounds Pyrethrins and Pyrethroilds (toxicity of, by pT classification) IT' 50-00-0, bioIogi'caI studies 5C>-06-6,,biological studies 5tJ-29-3',, CS LO' SO DT PY LAi 50-78-2 51-28-5, biological studies studies 54-11-5~ 54'-85-3 55-63-Ci 56r38-2 57-24-9' 57-27-2, biological biological'l studies 58-Ct8-2, biological biological' studies 58r73-•1' 58-89-9 67-56-1,,biologi,cal studies 67-64-1„ 71-23-8, biological studies 71-36-3,, biological studies 72-20-8 74-95-3 75-60-5 76-44-8' 76-57-3 77-67-8 78 9"••-3', bioLogicall studies 79-«6-1i, biological' studies 81'.-81-2' 83-79-4 B5*-fjfj-7 86-88-4 87-OD-3' 93-58-3 96-33-3 97--77--5 98-01 1, biological studies 98'-95-3, biologica2' studies 1047-41-4, biological studies 11)ti-57-6 , biological studies 1106-46-7' 1U7-02-8, biological' studies 107-4i7-3', biological studies 1i07-1:3-1,,, biological studies 107-13- 6, biological studies 107-49-3 1110-85-Q,, biological studi'es 11i4!-rJ7-8 115r-29-7 119-6412 121-75'-5 123r54-6,,biological' studies: 1^3-91--1, biological studies 127-69-.5~ 13)D-26-7 13'1--11,-3' 1_T•'-06-2 142-96-1. 144-49-ii 298--00-0, 298-46-41 299-42-3 _Ci0--62-9 '02-17-i_i 309-00-2 333-41-5 7,&9-(8-2 .°,00-28..-7' 525-66-6 534-52-1 5-r 1-78+-6 628-63-7 91'5-3v)-4 1_•1"-27-5, biological studies 1T14-84-7 13r75,: =' +370-20-7',, biological studies 14n3-66-3 3116-76-5 6998-6~!-3' 7440-28ro, biological studies 7487-94-7, biological studies 7,,42-_7-< 7645 25-2 7646-85-7, biological studies 11ao43-35-3,,biologi,cal' studies 1ic,1p8, 64-2 ]C71'24'-50--2 12002-ia.3-8: 12789--4?3-6 :_?589-9' 8' S' 53179-11-6 61102(3-24-8 (toxicity of'.,, by pT classifir-ation). 87491343: biological studies 5aj-49-7' 51-4v'-4 51' 55-8, bi'ol,ogicali 5ti-2.3-5y,biological studies studies 57-42-1 57-55-6, studies 58-1'5-1 58-55'-9, 60}57-1' 60-80-0 62-73-7 biological studies 70-3r.1-4i biological studies 71-43-2, 12
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ANSWER 8 AN CA LC)1 (':1J): :145=66n TI! Erythema-inducing effects of solvents following epicutaneous AU adlninistration to man - studied by laser Doppler fll'owmetry. Wahlberg, Jan E. CS Dep. Occup. Dermatoll.,, k:arolinsk.a,Hosp. LO Stockholm, Swed. SO Scand. J., Work,, Ernviron. Health, 1(:1(3') , 1:,9, 62 SC DT CC IS 4-3 (Toxicology) J SWEHDO rJ355-31,4C) PY 1984 LA Eng AB The irritant potential ofl chems. is,usually assessedlby visual scori~ngl, but the laser Doppler fliowmetry (LDF) was introducedifor thee assessment of erythema, The method is noninvasive and'allows conti'nuous recording. Eleven solvents were applied for .ltoreq.5 min, to the volar forearms of a man and the kinetics of the,response iss shown. For 7 solvents (DMSO Q67-68-57, trichloroethylene C79-C)1-6], hexane C114-54-3]i, CC14 C56-23'-5]', toluene C1lru8r88-a?, 1,1i,1-trichloroethane C71-55-6], 1,,1',,2-trichloroethane C79-00-51), an increase was found over the pretreatment val'ues,, whereas 4 solvents (Me Et ketone C78-91'-3]„ EtOH 164117-5],,propylene glycol C57-55'-67, distd. water) did not influence blood flow. Tihe findings are discussed in relation to the macroscopic pi,ct'ure (whiteni1ng,and erythema) and in relation to previous studies of the edema-inducing effects,of the,same solvents on man and eaptl, animals. Thus,, LDF'is well worth tryingi in cases of' margi'.nal irritancy andl for predictive testingy since it seems to be more sensitive and reliable than thee naked eye. KW erythema solvent laser Doppler flowmetry IT Doppller effect (lasers iin, of', solvents skin-.irritati'ng, acti'vity) IT Toxi,city. (of' solvents, to skin, 1'aser Doppler flowmetry in study of) I',T Solvents (toxicity of, to skin, laser Doppler flowmetry in study of) IT Allergy (contact, from solvents, laser Doppler flowmetry in,study of)'. I'TI Skin, toxic chemical' and physical dLkmage (irritatiiony from solvents,, Paser Doppler fllowmetry in study of) I',T 56-23-5, bi.ological, studies 57-55-6, biological studies 64-17-5„ biological studies 67-68-5, biologicali studies 71-55-6 7$'-93-3„ biologilcai studies 79-00-5 79-r71i-6, biologicali studies 108-88+-Z , biolagicall studies 1'1U-.°./4-", h;i,oloqi;cad, studies (toxicity of, to skin, laser Doppler flowmetrv in, study of) QD %J' ~ ~ ~ . ca ~ 1=
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ANSl4ER 9 AN. TI, AU CS LO SO SC DT CO Is F'y LA AE CA 101( 1h,) .105585b Urethan (ethyll carbamate) alone Iversen„ Olav Hilmar Inst. Fathol.,, Univ. Oslo, Oslo N-r}«27/1, Norway Carcinogenesis (London), 4~6 (Toxicology) ai CF2NGDR ia 14 :-":34 1984 Eng Ninei is carcinogenic for mouse skin 5(7Y, 911-15, groups of '2:hairless mice 016 males and 16 females in eachJ were painted on the back skin with .,apprx.20U mu.L soln. of urethane C5'1-79-6]', twice a week. for up to,58 wk. The followingitreatments were givent acetone C67-64-1]' alone, propylene glycol C57-55r6:] al!one, 10% urethane in acetone„ 15Y.'urethane in propylene glycol, 2O'/.' urethane in acetone, :307% urethane i'n propylene glycol, 40% urethane in acetone, 75y urethane in propylene gliycol, and .appr:r.l0rD"1.: melted urethane. Histol. examns. revealed no development of general epidermal hyperplasia or inflammatory reactions. Tumors developed in sk:in,, liiver, and lymph nodes, and 1 mouse also developed leuk.emic infiltrations in kidtneys and lungs. The rate and yiield of skin tumors were registered'and statistically ana'i,yzedL The no. of other tumors occurring was allso recorded. Thus, urethane is a tumorigen for the lung and several other organs;, it is,also a complete carcinogen f'or hairless mouse sk:in, even, in a dbse as low, as 10:/.' uretihane in acetone. There is also a significant dose-response skin Liver, neoplasmi Lung, neoplasm Skin, neoplasm IT IT (from urethane) Neoplasm. (from urethane:, in skin) Organ (neoplasm„ from urethane) ~ IT 51-79-6 ~ (carci'nogenici'ty of, in skin) ~ IT 57=55-6,, bioIogir_al studi;es 67-64-1, biological studies ~ (urethane carcinogenicity in skin in rel_ition to) . ~ ~ ~, Lymphoma hidney, neopl'asm relation, urethane carcinogenicity 14
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' ANSWER 10 AN CA101 ( 1i3) : 1,i>5173f TI Comparison of'the effect of three organic'solvent's on culitured cells AU Omori, Manabu,; Tak:agi, Hiromasa; Tanaka, Fumio; Hanamatsu„ Hiroyuk:i,; Nakagawa, Fumilb:o• Arimoto, Tomihide;: Ushimura, Yuki;ko;, Maicumi„ Heiji CS Dep. Rharmacol.,~Nippon Dent. Univ. LO Tokyo 1'02,, Japan SO Shigaku, 71(3), 497-503 SC 4-3', (Toxilcoingy) DT J CO SHIGAZ, IiS 0371-0068 Py 1983 - LA Japan AFI The cytotoxicity of propylene glycol (fiG) C57-55-6]„ DMF C68-12-2J, and formamide ('FMD) C75-12-7] was studied in cultured cei',ls. L cell nos. after reaction with 1'J5 FG', 1`/. DMF, or 1:: FMD for 24 h were 11400, 26,400, or 16,700;, resp. HeLa cell nos. after reaction with 1% PG', 17., DM'F, or 1XFMO for 24 h were 521.ti'mes. 103,,702', .times. 1'02„ or 429 times. 103, resp. The inhibitory efflect on the growth,of the cultured cells differed, withiFGy, esp. FfW HeLa~cel'1 org solvent t,oxicity; fibroblast org solvent toxi'city; org solvent cytiotoxicity;~ propylene glycol cytotoxici'ty;, DMF cytotoxici.ty IT IiT IiT IT ;, formamide cytoto::ici'ty Fibroblast HeLa cell' (org. solvents toxicity to:cultures of) Solvents (org.,, toxicity of, to culture& cell's). Toxiici;ty (cyto-, of' org. solvents) 57-55-6, biologicali studies 68-1^c-2', biologicall studies 5-12-7, bioliogical studies (toxicity of, to cultured celIs) . 15
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ANSWER 11 AN CA1O1(11)::85411,m T!I' Cytogenetic studies of'propylene glycol AU Yoshida,"Seiji; Sasaki, Mieko; Hiraga, Kmgo CS Tokyo Metrop. Res. Lab. Pubiic,Health LO Tokyo 160, Japan SO Kenkyu Nenpo - Tiok:yo~-toritsu Eisei Kenkyusho, (34Y, 388-91 SC 4-6 (Toxicology) DT J' CO TRENAF IS 0082-4771 PY 1983 LA' Japan ~ AS' Male mice (8 wk old), were given propylene glycol (I) C57-55r6} by stomach tube (4', 2, , and! 16 mg/kg) or water contg. I' (5, 10, and 20%J. As pos. controS, animals were injected with Busulfan i.p. at 25,, 50,,and 100 mg/kg. The animals were sacrif'iced!at 24 and!481 h or I and 2 wk after treatment and the bane marrow cells of the femurs examd., for chromosome aberrations. The incidences of ce1!Is with chromosome aberrations in the control were <?'.•T_•% in both espts. Similar incidences were obtained in the I group., Inithe EusuTfan-treated group, however, the incidences were 30-70%. Thus, I, did not induce chromosome aberrations in mice. KW propylene glycol chromosome aberration IT Chromosome (aberrations,of!„ prapylene glycol in relation to) IT 57-55-6, biological studies (mutagenicity of)', , 16
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ANSWER 12' AN CA101 (9) :6738.i:. TI Subacute toxici ty of propylene glycol i~n F3441rats AU' Okumura„ Masana o;, Yamada,, Sei ji:;, I',to, Masao;, Y.awamura, Norihi~sa; Hiramatsu,, Rei'j i' CS LO Aichi Prefect. Nagoya, Japan Inst. Public Hr3aSth SO Aichi-ken Eisei, Kenkyusho Ho, 34, 27-34 SC 4-3' (Taxilcology)', SX 17, 63 DT J, CO AKEKAK IS Ci515-78p3 PY' 1984 LA AB Japan Rats were given diet contg. 2.5, 5.0, 10.0, andl 2t7.GT. propylene glycol' C57-55-6]Ifor 13 wk to investigate its subaaute toxicity. The body wt. gainicurve, food consumption, and H20 uptake were similar i'niai1 groups., The 10 and 207. groups showed mark.edldeareases in the red blood cell counts, whereas the 5, 1U', and 20% groups showed increases in the leukocyte counts in the males compared to controls.. Hb and hematocrit values remained almost unchangedland serum compns. did not significantly alter. No histopathol. changes were noted in the treated animals. KW propylene,gliycol toxicity I'Ti Sex (propylene glycol toxicity in relation to). IT 57-55-6y biologi:caL studies (tos:i,city of, sex i'n rel'ati,on to) . ANSWER', 13' AN CA101(9):67185m TI' In vitro ocular irritancy testing. AU Douglas, Williiam HL J.; Spilman, Stanley D. ~ CS Sah. MedL, Tufts Univ. ~ LL0 Boston, MA 02111, , USA ~ SO Altern. Methods Toxilcol ., 1(Prodl. Saf., Eval,. ), 205-30 ~ SC 4-3 (Toxicology) ~ DT J CO: AMTOEN Cj IS 0737-402X k0h PY 1903 QD LA Eng AB Using a, 51Cr-release assay„ the cytotoxic, poternci~es, ofl 56 test substances were evaluated in corneal endothelial cell a±rltures. The test su.bstances were elected'primarily on the basi,s of having a well-characterized irritancy to the humanior rabbit eye. Nonirritant s and moderate irritants were inciuded, as well as severe irritants., Some substances were used because of theiir well-defined mechanism of action. Com. prodLrcts and mi;;ts. were included among the test substances. Mulitiple assays were performed, to characterize, interassay variabill',ity. A'pparent,ly„ the cultu!red eornea,l endathFliall cells correctly respond to nonirritants, although they may be 17
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relatively insensitive to the class of' fixitives which were ranked with nonirritants., Some substances were nontoxic at high doses which were limited by their aq, soly!. All of these substances,were nonirritants, allthougti quinacrilne (1) C8'-89-671 produced corneal opacification in some individuals chronically ingesting this drug., Lactate dehydrogenase leakage, aminoisobutyric acid'uptak.e, and Rhodamine-123 uptake assays for cell' viability were aliso, described. For di'agram(s), see printed CA Iissue., KW chem toxicity cornea assay; eye irri'tation chem assay IT Animal tissue culture (of' cornea~, chems. toxicity to, assay for) IT Chemicals Tannins Carbon black, biologicali studies (toxicity of, to! corneal endbtheliall cell'. cultures, assay flor) IT' G!uaternary ammonium compounds, biological studies (alkylibenzyidi'methyl,, chlorides, toxicity ofl, to corneal' endothellial cell cultures, assay for) IT Soaps Soaps (castile, toxicity ofl„ to corneal' endothelilal cell cultures, assay for) IT Eye, toxic chemical and physical damage (cornea, chems. toxicity to endotheliial cells of, assay for) IT Toxicity (cyto-, of chems., to corneal, endothelial cell cultures, assay for IT IT 3„ biological studies 1'0-1-2-1-1I, biological studies. 108-224-7' 1'08-:'1-6,, biological studies 108-95-2, biological' studies 111i-.T-•Ci-- 8' 119-36-8 1-.fi=--S 127-i i9,-3', 151-41--7 635-65-4!, b i ollcq i cal studies studies 7611-90-5 1310-58-', bi,oioqi,ca.li studies bioiogical 1'36-21i-6 'Jti58-23'-4 7447--4CS--7, bioliogical studies 7647<)1--Cy, biological studies, 7647--14-5,, bioLogical ~D studies 7664-97-9', bioIoyica.l studies 7h81-52'-9 7697-- -2, - ' ~ biological studies 77 4-1, biollogical studies 7757-31 - ~ biological str-idiies 7757 8'-7 7761 88-8, biological studies ~ 77825~r 5,~ biological studies 9~ia~ ~_.-1 "c~) 65--6 ,tl~ 4= 9' 1r?r74 5-1,, biollogical studies 66281-i!s! - 715.8-19-7 ~ (toxicity of, ro corneal endothellial cc11 cultures, assav +lor) w ~ ~ Eye, toxic ctiemical and ph,vsical, damage (irritation, fro(n chems., assay for)' 50-00-0, biologi',cal studies 50; 21-:i, biological studies 5(!-99-7', biological studies 51-3'41s 56-81-5, biologicai studies 57-55-6, biological studies 64-1i7-5, biological studies 64-19~-7,, biological studies 67-56-1, biological studies Ei7-61-0,, biological,studies 69-72-7, bioliog,ical, studies 71-36---" biological studies 75-65-0, biological studies 76-C)3-9,, biological studies 77--a2-9,, biol'ogical studies 79-47--6,, biological studies 83-89-6 1C)^c-71-6„ biological studies 1U7--15- ~I
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ANSWER 14 AN CA101 (9,) : 656Q3x TI': Chloramphenicol-propylene glycol toxicity following constant intravenous infusian in horses AU Spurlock,, S. L.;, Fowers,, T. E.; Varma, K. Ji; Fowers „ J. D. CS Dep. Vet. Fhysiol. F'harmecol.„ Ohio State Univ. LO Columbus, OH 43210, USA SO VOt. F'harmacol,. Toxi,col,., Proc. Eur. Assoc. Vet. Pharmacol. Toxicoli.,, C',Congr.]I, 2nd, Meeting Date 1982, 69i-6. Edited by: Fuckebusch,. Yves; Toutain„ P'lerre-Louis;, f;.orita, Gary D,. AVI: Westport, Conn. SC 1-5 (Pharmacology) DT C' CO 51YHA9' F'Y1981LA Eng A'B Administration of' ehliorampheni,col CI56-75-77 in propylene glycol C'S7-55-67 to Streptococcus zooepidemicus-inflectedlhorses revealed that the,solvent has toxic effects which resulted in the death of some of the animals. The most consistent fkndings on necropsy were moderate,to severe inf'lammation along the,entire intestinaL tract andl ecchymotic hemorrhages on the serosall surface of the small intestine. An i~mmunosuppressi,ve effect of the antibiotic was also noted. KW Streptococcus infection horse chl'oramphenicol,;, propylene gliycol chloramphenicol solvent toxicity IiT Immunasuppression (from chloramphenicol, in treatment of Streptococcus rooepidemicus, infection of' horse) IT Streptococcus zooepidemicus (infectiioniwith, of horses, ahloramphenicol-propyiene glycol treatment of', toxiici,ty in relation to) IiT Horse (Streptococcus zooepidemicus infectioniof',, chlorampheni,cal-propylene glycol treatment of, toxicity in, relation t;o)' IT 57-55-6, bi'ological studies (as dr'ug vehicle, chSoramphenicol' treatment of', Streptococcus zooepidemicus infection ofl horses with, toxicity of) IT 56-75-7 (Streptococcus zooepidemicus infection ofl horses treatment with propylene glycol contg., toxici'ty from)
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ANSWEF' 15 AN1 CA101 (2):1'1738b TI Anaerobic toxiciity testi'nqiof' several soft drink additives. AU CS LO SO Wiitkowskil„ Peter Ji. ; Jeris, John SI. Dep. Public Works, Nassau Cty. Miineola, NY' 115011, USA. Proc. Ind. Waste:Conf., Volume Date 198u•, 8th, 39--45 SC SX 60-1 (Waste Treatment and Disposal) 17 DT CG IS J PIWCAX 0073-7682 PY 1984 LA Eng AH No inhibition of biogas prodn. was,obsdL with Na benzoate C532-32-1I 83.3, gum arabic C904D'-U1'-5] 83.3, citric acid C77-92-9] 83.3, EDTA CbCr;-U0-47 83.3 „ and caffeine G58-08-2]', 8.3 mg/L. 1,2-Propanediol C57-55r6]' may be inhibitory at the 83.3:mg/L concn, tested. The 12.5 mg/L concn. of' CI producedlinhibition in alli runs; however, during the 55 day study it appeared that the microorganisms became acclimated to the stressedlenvironment and proceeded to convert the substrate to biogas,approaching the cumulative prodn, of theilr fed controls. Piogas prodn. was severely i'nhibited when caffeine (8.3 mg/L) and citric acid (8~.3.3 mg/L) were contacted with C1 (112.5 mg/l1). 1,2--Fropanediol (83'.:3 , mg/L) contactedi with CI (12.5 mg/L) produced varying data and' should be retested before arny definite eorncl'usions are made. The inhibitory effect of C1 CL2.5 mg/L) on biogas prodn. was si,gniif'icantly reduced in the presence of' EDTA (83.3 mgdL)'., The hi'ghireproducibid,ity of bi'ogas prodn. data demonstrates the precision of the serum bottle tlechnique for evaluating anaerobic toxicity. KW anaerobic toxiciity soft drink additive; benzoate soft drink anaerobic toxicity; caffeine soft drink anaerobic toxiicity; EDTA soft drink anaerobic toxiciity;. gum arabic anaerobilc to>:icity;: citric acid anaerobic toxicity IT Beverages (additives,i,n„ anaerobi'c toxicity to) IT Gases (bio-,, anaerobic generation of, soft dri,n4; additive inhibition of). IT 7782'-5(r-5, biological studies (anaerobic toxicity of'soft drinic additive in:preser•ce of) IT 58-Ci8-2, biological studies 60-00-4, biolociicali stuoies 77-92-9, biol:oqical stu.diies, 5_---_2--1' 900i-i-p1-5. (so-ft drink additive, anaerobic toxicity to), IT 57-55-6, biologilcal studies (soft drink add'iti've, anaerobic toxilcity to,,, chlorine etfect on) ~20
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ANSWER 118 AN CA100619) : 1I51023te. TI', Ascorbic acid antagonismiagainst perturbations in rat erythrocytess caused by propane-1„2-dio1 ingesti~on AU Ahluwal i a, F'ushpa:;, Amma, M. K. W. ; Sareeny, 1•:. N., CS Dep. Biochem., PanjabiUniv, LLO' Chandigarh 160014, India SO Life Sci. Adv., 2('1), 69-74 SC 1-12 (Fharmac-ology)' S x, 18' DT J CO LSADDN F'Y 198:3 LA Eng AB The protective effect, of' ascorbic acid 15C)-81-73 against the toxicc effects of propane-1,2'-diol C57-55-67, a drug solvent, were examd. Feeding rats ascorbic,acid reversed the effects of propane-l,2-dioll on the,total leuk.ocyte count and the reducedlglutathi'one C70-18-81 content of'erythrocytes. The action of ascorbic acid on the effects of propane-t,t+-dioli on erythrocyte membrane (Na+-}(+-Mg2+),--ATFase (EC 3.6.1.3) C940v-8v-37, 5'-nucleoti'dase (EC 3'.1.:,.J) C9027-73-0],, acetylcholi!nesterase (EC 3.1.11.7) C9000-81-1], acid pHrosphatase (EC a.12'.1,) C9o01i-77-8], and total proteins was also dbtd. ApparentIy', ascorbic acid protects the oxidn.-redh. system of' the erythrocyte by providing more reducing units (NADF'H) to maia-,tai,n the normal Ievel, of reduced glutathione which is perturbed by propane-1.2-diol. KW propaned7oli toxicity erythrocyte ascorbate; glutathione erythrocyte propanediol, ascorbate IT Proteins (of' erythrocyte, propanediol effect on, ascorbic acid''inhibition, of). IT Leukocyte (propanediol effect on, ascorbic acid antagonism of) IiT Erythrocyte (propanediol toxicity to,,ascorbic acid antagonism of), IiT 57-55-6, biological studies (erythrocyte toxicity ofl„ ascorbic acid antagoni,sm of ) IT 70-18-8, biological studies 9<]op-8I1-1 900aj--(3,.--3 9irp1-77.-8 9027-73-0 (of erythrocyte, propanediol effect on, ascorbic acid inhibitioni of )' IiT 50-81-7, bioloqir_all studies ~ ( ro anediol toxicilt to er throc te anta onism b ) p p y y y q y , 21
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ANSWER 19 AN CAI00( 1I6) a 122979e TI Inks for skin marking CS Daiwa, Makanto Kogyo F;., K:. LO Japan F'I Jpn. Kokai Tokkyo Koho JF' SB/154772 A2 C8371154772]I, 1,4 Sep 1983, 4 pp- AS Appl. 82/38395, 10 ' Mar 1982'. CL C09D111/0<1 SC 42-12 (Coatings, Inks, and Relat,edlFrodLncts) SX 17,, 63 DT P CO JKXXAF PY: 1983. LA Japan AH Inks with low toxicity, useful in marking of' ' sk.inifor surgery or of fruits and vegetables, contain aq, a1cs.,,glycerol, propylene gyycol (I',), C57-55-6]I, and/or polyoxyal'kylnes as regulators, and basic'dyes. A suitable ink,contauns methyllene blue C61-73-4] 3.5, EtOH 501, food-grade 1 20, NbOBz 1, tannic acid'Q.S'„ and H2r) 50parts. KW dye low toxicity;, surgery skin marking dye;: methylene blue compn IT T nontoxic; propanedioi dye compn nontoxic I k n s (with 1'ow,toxicity, basic dye-polyol-alc.-water compns., for IT marb:ing,sk:inior agricultural products) Dyes IT' (basic, in inks with low toxicity) 56-81-5, uses and miscellaneous 57-55-fs, uses:and miscellaneous 25322-68-3 25322-69-4 IT' (lin inks with llow to:<icity) 61-73-4' 54'8-62-9 569-64-2 2465-27-2 80fj4-87'-.T.. 39384-3'4-4 (inks, with low to.ilcity) ^?'
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ANSWER 20 AN CA99 (21) ::1,7i!894f TI Response of isolated hepatoeytes,to organic and inorganic cytotoxins AU Story, D'. L. ; Gee, S. J'. g Tyson, C., A. ; Gouldl,, D'. H. CS SRI Int. LO Menlo Far4;,, CA, USA SO J. Toxico1. Environ. Healith, 11(4-6), 483-501 SC 4-3 (Toxicology) DT' J CO: JTEHD6 IS 0098-4108 F'Y' 1i983 LA Eng AE Chems. were tested for cytotoxic response in isolated hepatocyte suspensions from young male rats., Hepatocytes were incubated in,the presence and absence of the test chems. in closed'vessels flitted witfii side arms for seriali sampling for .ltoreq.5 h at , 37,degree. with gentle shaking under an 0::C02 (95:5) atm6 The parameters evaluated were glutamate-oxaloacetate transaminase and lactate dehydrogenase release from,the cells„ Tirypan blue exclusion, cell count, urea synthesis capability„ and steady-state ATP levels. All chems. cytotoxic,in animals following single or short-term repeated exposures caused signiifi,cant changes in .gtoreq.l of', the parameters at 0.01-10 mM'. Dimethylnitrosamine C62-75-9,]!and thioacetamide L6i-55-:,1,were not as potent in the isolatedlcell system as expected from their in vi,vo Hepatotoxilcity, a.nd the quant. changes aroducedi with thioacetamide in the hepatocytes were marginal, even at 10 mM. The soLvents tested-EtOH C64'-Q7-5], acetone C67--64-17, DMSO'. C67-68-51„ andl propylene, glycol CI57-55-61-were without eff'ect. Thus, ilsolated!hepatocyte suspensions are useful for thee identification of cytotoxins i'n general and hepatoto>:ins in particular, but their capabillity for yielding a,quanta irndex'of cytotoxic potentiali for div,erse, chem. species remains to be demonat,rated. KW hepatncyte chem to:cicity' IT Toxicity (of chems., to hepetocyte), IT Solvents (toxicity of, to hepatocyte) IT Liver, toxic chemical and physi'cal damagA. (hepatocyte, chems. to;;ici,ty'to) I!T 5(j-G1-7, biologiical studies 51-28--5. biological studies 56-'-7'_, 5, biological studies 57-55r6,, biological stwidies. 61-02-5 62'-55-5. 6:--7.5-9 64-17-5, biological studies 64-69-7 67-56- 1, bdolo:gicall studi,es 67-6'4'r1, biological studies, 67-66--3, bi:olaqica:l, studies 67-68-5, biollogp.cal studies 75-3::,--4, biol!oq;ic al studies 75-6Y-7 79-E0-5 96-09-3 10i3.-42-5,, biologica1 s u ii-_; 1iJ7-18-6, biological studies 111-42-2, biological'. studies 1:_6--72-7' 151-50--u 02--C 1-2, biologiical studies 11b2-63-C 2i 51-60-7 2ti°i1--62--9 '4'7-79-8 4^,is0-78-0' 4'68°-14'•-7 !'3'9--97-6,, bioloqical , sl:udies 7440-4._:-9, b:iological stud,ies 7 84•-4-:-5 1L1!1i0-01-o =1492-8 55o68 94-5 (1'!7 l_i'i:y of, to hepatorvtP) 87491354
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ANSWER 21 ANI CA99(21):1'70718b TI ExfoLiative cytology as a reftnement of the Draize eye irritancy test AU W'alberg, James CS' Lab. Anim. Res., Cent., Rockefeller Uni'v. LONewi `dork.„ NY1002i1, USAS0 Tioxicol. Lett-, 18C1-2)'„ 49-55 SC 4-1 (Toxicology) DT J' CO TOLEDS ISI 0378-4274 PY 1983 L-1 Engi AB Collection ofl exfoliated cells from the eyes of' rabbits was performed in conjunction with the Draize ocular irritancy test. At stid, intervals after exposure to alcs. of known i'rritancy, exfoliated ,_e11s were retri!eved from, the conjunctival sac with a distd. water corneal rinse. These cells were fixed and then counted, centrilfuged and stainedlby the method of'Fr'apanicolaou (1977). The:noe ofl cells which were retrieved correlated well with Draize test scores. This noni'.nvasilve,modifi,cation ofl the Draize test was well tolerated by rabbits andlprovides an objective assessment ofl ocular i'rritancy. I't is hRped that this refinement of the Draize test wi11I reduce the nos. ofl an;.malis used and provide more objective data upon whichi validation procec-!res for alternative methods can be based: KW Dr'a,ize eye irritatkon exfoliiate cytol; alc eye irritation test IT A1'eoholis, biologilcal studies (toxicity of, to,eye, exfoli,ated ceIlis in refinement of Draize irri'~tarncy test in relation to), IT Eye, toxic chemical' and physicall damage (irritatiion, flromia1cs., exfoLiaked cells in, in refinement of Drai:ze irritancy test): I',T 57-55r6,, bi,c:ogical studies 71-3E,-3, bioiogical studies 711-4'1-fj, bi'ologi'eaI studies 107-18-6, biological studies (toxicity c-F', to eye, exfol'iatedi cells in reflinement of Draize irritancy t.-st in relation to), 24
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ANSWER 22 AN CA99(17):,1"8295a TI Propylene:gDycol contents of commercial foods AU Yamada,, Toshiharu;, Osada, Yu4:io;, Nak.aokay Tadayoshi;, Ito, k:azutosh'ei CS 4,".anagawa Pref. Publ. Health Lab. LO Yok:ohama,i41, Japan SO Shokuhin Eiseigaku Zasshi, 24(3), 340-3 SC 1!7•-5 (Foodl and Feed Chemistry); SX 4 DT J CO SKEZAP IS' Q41,5-6426 PY 1983 LA Japan AB Propyliene glycol (I) L!57-55-6] as a food additive was detd. by'gas chromatog., in 280 ' samples. A very few samples,(3 out of110) of noodles contained 2.1-2.9% I, though the permitted limit is 2.c)Y.. Most samples of'smoked squid, fish-paste products, confectionery, and i'ce cream contained no I. KW propylene glycoll foodl noodle IT Food Pasta (propylene gliycol of, toxicity in.rel'ation to) IT 57-55-6, biologi'cali studies, (of foodl„ toxicity in relation toY ~•':J,
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ANSWER 23 AN CA99(13)'::100541q TI The effect of chemical carriers on avian LC50'too-cicity tests. AU Gile, Jay D.,; Beaver, Joann B.;i Fink., Robert CS Corvallis Environ. Res. Lab., Environ. Prot. Agency LO Corvallis, OR'973,1.3, USA SO SC DT'. CO IS PY LA Bul l. Environ. Contam. Toxicoli.,~ 19W-2-02' 4-3 (Toxi'cology) J, BECTA6 oL)67- 4861, 1983' Eng AB The use,ofl corn oil, propylene glycol C57-55'-67, CM-ceIlulose, C90Q4-y2-47 andIH2O as carriers of the pesticides carbofuran, CI) C'1563-66-27, dursban, C2921-88-2] and endrin C',72-2C/-87 in dietary studies with bobwhite quails and mallardldUc4r,s showed that carriers had an effect on median 1'ethali concn. (LC5(D,), values since dose-response curves changed with difflerent carriers. With few, exceptions, groups of birds presented'with corn oil consumed liess fbod than'those presentedlwith the other 3 carriers, but growth was not affected by reduced consumption., Anal., of feed samples indicated noleffect of any carrier onitest chem, concns., in feed. For diagram(s), see printed CA'Issue. FEW pesticide carrier toxicity test bird I'T IT IT IT IT i I Co rn o l (as pesticide carrier in dietary study, avian toxicity in to) To;;i¢ity relation (of pesticides, to birds, chem. carrier effect on) Quail Anas platyrhynchos (pestieide toxicity to, chem. carrier effect on)', Pesticides (toxicity of, to bird5, chem. carrier effect onY 57-55-6, biological studies 77T2-18*-5,,, biological studies 004-32 -4 (as pesticide,carrrier in dietary study,,avian toxi,citv in relation to)' IT 72-20-8 156'~-66-2' 2921-88-2 (toxicity of, to birds, chem., carrier effect on). 2 (i
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ANSL+7EF: 24 AN CA99(7):47577c TI Harmlessness of pollymer-based complex antibiotic drug forms for agri,culturaU animals AU P'arfenov, I. S. CS Lab.: Antibiot. MiRol, Vses., S-kh. Akad. LO Moscow, USSF(' SO Byu11. Vses. Inst., Eksp. Vet., 42, 47-9 SC 1-5 (Pharmacology) DT J CO EtVEVAS I S PY LA AB t?:i66-4899' 1981 Russ Polyethylene glycol C25322-68-37, 1,2-propylene gQycol , C57-55-67, their combinationiwith:di1biomycin CY1111-27-97 and ditetracycline C295Cr~70-11]!, resp. , as well as the: other antibiotics andl sulfonamides tested appeared to be essentia111y nontoxic to mice, rabbits,and guinea pigs. K•W, pol'yethySene~g0.ycol' antibiotic toxicity; propylene glycol antibiotic toxicity;~ sulfonamide toxicity IT Toxicity (of' polymer based antibiotics) IT Antibiotics Su 1 f onami'des (toxicity of pol!ymer based) IT 56-75r7' 1111-27-9 2950-70-1 4154-10'-3 81031-57-4 85666-81-5 85666-82-6 85666-83-7 85666-94-0 85666-95-1' (toxicity of polymer based) IT 57-55r6, biological studies 25322-68-3 (toxicity of, as;excipi,ent for antibiotics), 27
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ANSWER 25 AN CA98(23J.192854z TI', Comparative metabolism and di'spositi~on ofl ethylene glycol monomethyl ether and propylene glycoli monomethyl ether in male:rats AU Mi17 er',, 8. R.; Hermann,, E. A.;, Langvardt, P. W'.;, McKenna, M. J.; Schwetz, B. A. CS' ToxicoT,. Res. Lab.,, Dow Chem. USA LO Midland, MI 48640, USA SO Toxicol. Appli. F'harmacol., 67(2), 229-37 SC 4-3 (Toxicology) DT J CO TXAPA9 IS' 0044'-OOSX PY' 1983 LA Eng. AB There were pronounced differences in the metab. and disposition of 14C-labeled ethylene glycoT, monomethyl ether (EGMEY C109-86-47 or propyliene glycol monomethyl ether (PGME) C1'20-67-8]' by rats given a single oral dose (11 or 8.7 mmol/kg). Approx.,;0-60V,:of the administered 14C was excreted in urine, andi.apprx.12X was eli'minated as 14COT within 48'h of' administration of' EGME'. For PGME, only 10-20% of the admi'nistered 14C'was excreted in urine, and150-60% was eliminated as 14CO2 within 48 h. methoxyacetile acid C625-4'5-6]IWas the primary urinary metaboliite~of EGME, accounting for 80-901G of the total 14C in urine. PGME, propylene:g;lycol (1,2-propanediol) C57-55+-6], and the sulfate andl gluicuronide conjugates of PGME were identifi'edl in urine of' rats given F'GM'E. Si~nce methoxyacetic acid causes the same spectrum of toxicity as EGME, it is likely that the adverse effects,of EGME'are the resuIt,oft i~ts metab., to methoxyacetic acid., Differences in routes of' metab. and types ofl metabolites appear to be the underliying basis for the markedly different toxi.col.. properties ofl EGME and PGME. KW ethylene glycol monometF'oyl ether metab, propylene glycol monomethyl ether metab; glycol ether toxicity IT 625-45r6 IT (ethylene glycol monomethyl to)' 109-86-4 1.=:20-67-8 ether metabol,ite, toxi'city in relation I T (metab. ofl) 85684-22'-6 85604-L3-7' (propylene glycol monomethyl ether metabolite) ~. IT 57-55-6, biolloq0.cal studies ~, (propylene glycol monomethyl ether metabolite, toxicity in relation to), ~ ~ W 2 13
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ANSWER 26. Ary, CA99 (19 ) :i159236b TI Mutagen formation inideepffat fried foods as a, f'uncti'onf of frying conditions AU' Taylor, S. L.gi Berg, C. M.; Shoptaugh, N. H.-; Traisman, E. CSI Food Res. Lnst., Univ. Wisconsin LO Madison, WI 53706, USA SO JAOCS, J. Am. Oil Chem. Soc., 60(3), 576-80 SC 1'7-W (Food and Feed Chemistry) D T J' CO JJASDH PY 1983 LA Eng AE+ Deep-fat fried foods possess low 1'evels of mutagenic activity, arid severely abusive frying,condi'ti,ons must,be employed to;obtain appreciable levels of" mutagenic: activity. With French fri'ed potatoes:, either excesstvely long frying times (35-40 ;min) or abnormally high frying temps. (above 41,0.degree:,F or 21S1.dpgree.C), were necessary to generate appreciable levels of mutagenic activity (?2.5 times the spontaneous mutation rate). Repetitive frying of 45' batches of French fried potatoes,or onion ri;ngs,in the same batcM of' shortening elicited no increase in mutagen flormat'inn.Repeti'ti,ve frying of',fish fillets in the same batch of shorteni~ng,resulted in the generation of appreciable levels of mutaqen~(sY i~n both the acidic: and basic CH2CIZ exts. Increased mutagenic activity was noted by the 7th batch., Fish fi'Ilets,obtained from a local restMurant at sel'ected' intervaIs during, a 1'-wk period of use of'': a particular batch of' frying oil contained much lower levels of mutagenic activity., h::W IT IT! mutagen f'ryingi potato fish onilonl oil mutagen food frying Mutagens (formation of, in flri,ed foods, frying,conditions effect on) TaSlow ' IT Cottonseed oil (frying oil contg., mutagen, formation, in food fried in) Fish i O T n on Potato (mutaqeni'e activity of' fried, frying conditions,eflfe_t on) F.i C oo n3 (flry!ing, mutaqen formation in foods during, fryingi conditions ff t ) IT ec on e 57-55-6, biological studies 77-92-9D, monoglycer.de dbrivs. ~, 12'1-79-9 128-37-0, bilolog:'.eaL studies 2;;013-1i6-3 ~ (fryingioil contg,, muta.3en formation in faod fried in) ~ ~ ~ '9
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ANSWER 27 AN CA98I(~1'9) : 1i55979y TI Superior heat transfer fluiids, for solar heating and cooliingi applications. Results of acute orai toxicity determi'nations AU Parts, L.;, Conine, D. L. CS Dayton Lab., Monsanto F:es. Corp. LO Dayton, OH, USA. SO Report, MRC-DA-1096-Vo1,.1'; Order No. DE82Ctr?2758, 36 pp. Avail. NTiIS Fromu Energy Res. Abstr. 1982, 7(1'7), Abstr. No. 44835 SC 4!-3 (Toxicoliogy) SX 52 DTI T PY 1981 LA Eng AD Acute oral toxicity tests were conducted in rats with 22 heat transfer fluids used in solar collectors, including 3 f',luids that had been used'iin collector installations for 1-3 yr. The Gosselin acute oral toxicity ratings of' the fluids range from 1i (practically nontoxic) to 3 (moderately toxic); most fluids are rated 1. Accident al' ingestion.of' LDs is not very probable in normal use. By Gossel,iln's rating system, undil;d. ethylene glycol C1Cl7-21-17-basedl fluids are classified as 2 (slightly toxic), whereas,propylene glycol C57-55-6]-based fluids are rated 1. The use of" ethylene glycol- and propylene gllycol-based fluids for 11 yr, and of an aliph, hydrocarbon type fliuid for 3 yr, did not increase their acute toxici,tyy significantly. KW solar heat transfer fluid toxicity I'T'Toxi'city (of solar heat transfer fluids)', I'Ti Hydrocarbons„ biological studies (solar heat,transfer fluids contg., toxicity of) I,Ti Cooling apparatus. Heating systems andlHeaters (sol'ar, heat transfer fluids for, toxicity of)', IT 57-55-6, biologica:l' studies 1'07-21'-1, biol'ogical studies (solar heat transfer fluids contg., toxicity of) ~fi.
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ANSWER 28: AN CA9807'):'1,42049v TI Effect o4 variouis:food additives and Linear alkylbenzenesulfonates on metabolic cooperation i'n Chinese hamster cells AU Yoneyama,, Masako; Nakao,, Toshiko; Hiraga, Kogo CS Dep. Toxicol., Tokyo Metrap. Res. Lab. Fubl'ic Health. LO Tokyo, Japan SO Tokyo-toritsu Eiisei Kenkyusho Kenkyu Nempo, (33), 544-6 SC 1,7-6 (Food and Feed Chemistry) DT J CO TRENAF I S p493'-449c? PY 1982' LA Japan AB Propylene,glycol C57-55-6] And linear alkylbenzenesul'fonates had a~ sliight inhibiting effect on metab. cooperation inicult'ured Chiinese hamster cel'1s. Thiabendazole, Na dehydroace+_ate, BHA, BHT, o-phenylphenol, andlphenyLhydroquinone had no effect. KW propylene glycol toxicity; benzenesulfonate toxicity ITi 57-55-6, biological studies; 98-1'1-3D, alkyl derivs. (toxicity of) - 1
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ANSWER 29 AN CA97(':11),:86'471s, TI: Design,,aonstructioni and operation of a simple inhalation exposure system AU Barrow, Craigi S'.; Steinhagen„ Wilil,iam H. CS Chem., Ind., Inst. Toxicol., LO Research Triangle Park, NC 27709, USA SO Fundam. Appl., Toxicol., 2(1),, 33-7 SC 4-3 (Toxicology) DT J CO FAATDF IS 0272-0590 PY 1982 LA Eng AB An inhalation exposure system was designed from an all glass aquarium with,a vol. of 391 L. A top,for the chamber was fabricated from acrylic plastic and Teflon with an inlet, outlet',, 5 sampling,ports, and handles., Supply air to the chamber was charcoal and HEPA, filtered. Air f'low through the chamber is horizontal and range from 50 to 200 L/min. Air flow,is measuredlby a gl'.ass tube rotameter and, regulated by PVC valves. Chamber air was HEPA andlcharcoal-fi,ltered prior to exhausting i:t to ambient air. The,operatin%characteristics of this exposure system were assessed usi'ng test atmospheres of' HCHO [50-00-07,, C1, n-hexane C11fJ-54-3]I, and an aerosol of propylene glycol C57-55r61. Expressed as percent of a central sampling point,, the chamber concns. of' HCHO,, Cl and n-hexane was 91!.6-103.,v7.. No, difflerences,in chamber distribution were noted at 78 or 1'3O: L/min, (corresponding to L2'and 20; chamber vols./h). For propylene glycol, the mass median aerodynamilc diam. at a chamber air flow of" 79 L/min vari~edlfrom 1.37 to 1.63 .mu.m. Similar results were found at 130 LJmi~rn. During mass sampli'ng,a concn. gradient was found flrom the inlet to the outlet of the chamber an&ranged from 55,to 997.'ofI the inlet conan., This inhalation exposure system is very suitable for acute or subacute inhalati~on;studies of gases or vapors but is only satisfactory for aerosol'~s under certain operating conditions. KW IT IT IT inhalation exposure system toxicol Tor:i!ci,ty (inhalation e;;posure system for) Chemica.Ts. (tc.xi,cit'y of, inhalation exposure system for). 50-00-0, biological studies 57-55-6, biologicali studies 10-54-3,, bioliogical studies (toxicity of, inhalation exposure s),stem forP, 32
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r _ ANSIdER' 30 AN TI C5 LO so SC DT Co IS FY LA AB F:I'W, IT IT T IT IT CA96,(21'):175B52p Quantitative correspondence between the in ofl teratogenic agents Braun,, Andrew G.; BLtck:ner,, Christine A.; Nichinson,„ Bradley Es. Dep. Radiat. Ther., Harvard Boston, MA 02115, USA Proc. Natl. Acadl., Sti. 4'-6 (Toxicoiogy)'. Ji PNASA6 r)027-8424 1982' Eng, Med. Sch. vivo and in vi,tro activity Emerson, Davi,d'J~.; U. S. A. r Seventy-flour teratogenic and ; 79(6), 1-256--60 28 nonteratogenic agents were te=-ted'in a developed'in vitro teratogen assay. The assay identified teratogens by their ability to inhibit attachment o-f' asci,tes tumor cells to plastic surfaces coated with conc.ana-valin A.. There was a qual. agreement between in vivo animal data and in vi'tro activity for 81 of 1rJ'2 agents (79%J. Quant. anal. showed a hi'ghly significant correlatiloni coef'f, of 0.69 9 between the inhi,bitoryy i'n vitro dose and the lowest reportedlteratogenic dose for 541of 6CYinhibitory teratogens. The,doses analyzed ranged over 5 orders of magnitude. These results were interpreted to mean that attachment inhibition in concert with other,, compSementary, in vitro assay systems can becomee a. useful method flor' the assessment of' the teratogenic pot.ential' ofl environmental agents, teratogeni,n vivo vitro activity Radiation„ biological effects (from teratogens) Teratogens (teratogenici'.ty of ) Environment (teratogens of, in vi',vo and in vitro activity in relation to) 50-ty2-2, 5o.-<t6--6',, biological studies 5Q• 14-6 50-23-7 50--24:-8 5U^-z8-2, biologi'cali studies 5D-32-B'„ biologi'cal studies 5U-33-9, biologicaI studies 5(:)-35-1 50-53-3, biol'ogical studies, ,°,rl'-55-5 50-76-0 5(1-78-2' Jly+-81I-7, bioSogical' studies 5(1i-9,9-7, biological studies 51Jr-12-7 51-2'il-8, 51-28-5, biologicali studies 51-4?-4 51-45--6, bi'ologi''caL studies 51-61-6,, biologtcal studies =2 SC1-4, biological studies 5"-06-5 53-86--1 54-11-5 54-36--I 55-48-1 ,--98-1' 56 3-5,, biologi,cal' studies 56 1'. .,6 65 , bioloqical studies 56 7,r-7 56-87-1„ biological studiea 541-0 57 .,0-1, biollogica1 studi'.es 57-._,C-4' 57-55-6, biological studies 57-92-1,,, biological,studi'es 58-q8-2, biiol,ogiical 5tudies ti8-15-1 - D-a ~' ~ r~ E-'8!-8 58-55-9,, biologi,cali studiEs 53-56-rY; 59-02-9 54 rr -2 ~ .-, E- '8!-8 59-4.'-8, biologi!cali stu_dies 59--67--6,, bi,ologi;ca.l ntudies :a'+-92-7., JPA bioliogacal studies 6p-tuo--4, biol:ogi.caI, st,.diles 41W biolm9dcal studi'es 6;3-91-2,, bilologica.l studies 64-1'7-5'. Q"jM biological studiies 641-g6--B 6,-4`5-2 67 66-_;'•, bi^1c,qi,cali studies ry 67--68--5, bir.ol.ogi'.eal studies .99 F.'5 -+ 71i--- bi'•_l.~qicai st!~.dies 72-'i7- 1 7' 2-', biologi_,,ali st id;:c.s, 7E-74-4 ~ c1-%o1-2 1~r?-90~-2 1ii0-9'1-&„ hioIogica:l atradi.rs bio1 ogir.._;i, ! EM
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studies 11,7-89-5 1'26-n7-8 128-37-0, biological studies 128-44',-9 130-95-0 1'9-q5'r9' 142-47-2 154-9 3r8 'ff2-79-4 309-00-2 a15-'8-0 4:.,9-14-5 554-13'-2' 569-65'-3' 6:L4-60-4 865-21-4 915-67-3 ', 1069-66-5 764'6-85-7, bioLog:icali studies 7683-59-2 8o64-77'-5 990o-11-7' 9C144' 1f.a-8, biological studies. 9004132-4 9005-49-6, biologicali studies 9vq5r68-6 90ii7-28-7' 119p0-17-2' 1'1097-69-1 12125-02-9', bi,oIogicali studies 14930-96-2 22144-77-0 2''214-92-8 2501'-16-5 --5101'-U2'-4: (teratogenicity of) 34
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ANSWER 31 AN CA96(1,9,) :'.15ln952e. TI Skin irritation by propylene glycol. AU Andersen, Klaus E.;: Storrs, Frances J. CS Dep,. Dermatol.„ Gentofte Hosp. LO SO SC SX D T CO Copenhagen, Den. Hautarzt, 33'C1), 1'2'-14 4-3 (Toxicology) 17, 62, , 63 J' HAUTAW ISI 001,7-847r) PY 1982' LA Ger AB propyl!ene glycol C57-55r63, Used'inifoods, medicine, and cosmetics because it is:a good solvent with moisture-regulating, antiseptic, and preservative,effects, may produce eczematous skin reactions of'a toxic and, more rareliy,, al'1'ergic nature. Pos. patch test reactions to propylene glycol are difficult to interpret. Allergic reacti'onss may be confirmed by a clear cl,in. rel'evanae,, repeated local skin provocation (usage test), or oral provocation. In patch tests with 84 patients and 100% propylene glycol, 5 of 12',patch test-pos. patients had allergic reactions, and17 had irritant reacti,ons.. When 248lconsecutive eczema patients were patch-tested with propyllene g1Nco1' in concns. of'1ry4, 20, and 2% in water, 2'of 5'with pos, l reacti'~ons in pat,chitests had'~an itchy eczematous eruption after oral provocation with,15 mL propylene glycol., SH:inireactions:to propylene glyaol! are rare, but the possibility of aIliergy should be recognized by dermatol'ogists since, propylene gllycol is used in,Iocal steroid andl other topical'prepns:. KW skin iirritation propylene glycol IT Skin, toxic chemical and physical! damage (irritation,, from propylene glycol, of humans) IT 57-55-6, bioliogP:cal studies (tox;i'city of, to human skin) 35
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AN! CA96(1'2)':I91674'u TI Method and composition for reducing the toxicity of acetaminophen AUi Nelson, Edward B. CS State University of New York, Research Foundation LO: USA, PI U.S. WS' 4307073 A, 22 Dec 1921I, 4 pp. AI Appl. 176418, B'Aug 1980 CL 424-10; A6SK31/165 SC 63-6 (Pharmaceuticals) SX 1 DT P CO USXXAM' PY 1981 LA Eng AB The toxicity of acetaminophen (I) O1h3-90Y2] is decreased by oral, i',.p., s.c., i.v, or i.m. administration of' a mixt. of I and propylene gl'ycol (11) C57--55-6] (0.3-12 g/kg of' body wt. ). The, ratio of II to I'is D,3-4G0h:1 (by wt.>. Other pharmaceutiIcal carriers or diluents can be used wi'th' this mi'.:;t. Thirty mL/k.g of': combined 11, II and' 0.,9% saline soln., (I and III in vari,ous doses) were given by i.p. injectiIon to,white mice. The survival, rate among,89 mice was 96% measured at 96 h after dosage (I'I-I' ratio was 7.5;,1). I!I',does not seem to have a toxi'c effect andldoes not adversely affect the analgesic properties of I. For diagram(s),, see printed CA Issue., F'W acetaminophen toxicity propylene glycol IT 57-55-6, bioi'ogical studies (acetaminophen toxicity decrease with) IT 103-90-2 (toxicity of, propylene glycol for decreasing) 3h
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ANSWER 3'3I AN CA96(9):6T865p TI Comparative study ofl. ethylene glycol, .alpha.-propylene glyaoli and glycerin toxicity AU, Guchok, M'. M. ;(3'iuchok, V. M. ; Mazalov, V. f.`.. CS Inst. Frobl. FCriobiol. Kriomed. LO, Kharkov, USSF', SO Kriobilol. Kriamed.„ 9, 36-4ti SC 4-3 (Toxicology) DT J CO KRKRDT IS 01''iJ-26h3 F'V'' 19811 LA Russ AB The toxicities of single doses of .alpha.-pr-opylene glycol C57-55r6], ethylene glycol C1h7-21-1], and glycerin C56-81i-5] in mice, rats „ and rabbits were dependent on the route and rate of' administration and concn. of' the compds. In general, propylene glycol was less toxic than ethylene glycol or glycerin, which were generalliy of' similiar toxicity. The~ safety of' these compds. as cryoprotectants or drugs i's,discussed. KW glycol glycerol toxicity health hazard; cryoprotectant toxicity health hazard IT HL=aTth hazard (from glycerin and glycols) IT Cryoprotectants (gIyceriniand glycols as, toxicity ofl) IT Toxicity (of cryoprotectants) IT' :,6--81-5, biological, studies, 57-55-6, bioIogical studies 107-21-1, bioloqicali studies (toxicity ofl)
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ANSWER'1 AN CA103(9):66333n TI Interpretation ofl cell toxicity data for the estimation of potentiali irritation AU Reinhardt, C'.A.; Pelli, D. A.; Zbinden, G. CS Swiss Fedl., Inst., Tiechnol. LO Schwerzenbach CH-86O3, Switz. SO Food Chem.: T©xicoI., 23(2), 247-52 SC 4'-3; (Tox;i,cology) DT a1 CO FCTOD7 IS 0278-6915'i PY' 1985' LA Eng AB Three cytotoxi~city assays were evaliuated using 57 chems. of various class ('inorg., and org. metal salts,, solvents, detergents, reagents, and drugs) which have widely different mechanisms,of cytotoxicity. Baby hamster kidney fibroblast (BHK-21'/C1:,) andl earliy (Keller) and late (MRC-5) passage human fibroblast were used to measure:cell detachment„ clioningiefficiency, and growth inhibition under subcon#luent culture conditions. For the majority of'chemsf for which comparisons were made, the,ranking order was roughly the same in all 3 ' tests and' with all ' cell types. However, for some chems.. specifi'c,growth effects coul'dlbe detected or excluded because the relation between the data from the detachment assay and that -from one of'the growth assays was,characteristically altered'. The ranking order resultiing from in vitro deta correlated better with thresholid limit values for human workroom air (TLV/TWA) than with LD5r] (rat, oral)',. Correlations with data from Draize skin and eye irrita.tion tests were not detd. since the available in vivo values were derived usingivarious dfifferent scoringisyst'ems. However, when in vitro data were used to divide the chems. into s3 crude class, ('i)' non.-irritant, (ii) mild to moderate irriitant, or (iii) strong or corrosive, and the resul'ts were compared withithe known irritation potential for skin, and mucous membranes deri,ved'from human exposure data, the in vitro data were :'>8rj'l% predictive of the i'n vivo elassificati,ons. k:W chem cell toxicity potential irritation IT IT IT IT Fibroblast (chems. t'o;:i.city to, potential irritation in relativn to) OD Chemilcals -a Detergents 06 Fharmaceuticals CD Soiuents ~ (cytot'o,.iici,ty of, potential irritation in reliation to)', Allergens (screening for, by cytotoxicity assays) ~ ~ Eye, toxic chemical and physical damage Skinq, toxic che.mi'cal and physical d'amage (irrit_ati'rnn, from chems., screening assay of cell toxieitv in relation to) IT Trace elements' (metals, cytotoxicilty ofi, potential iirri.taticn in r-ela.tion to) ~L,
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I'T 54-0O-U, bi,ol'ogical, 52-89-1 56-23r5, 58+-08-2,,bioIogical 6:3'-li8-3, biological 4r-- studi~es, 50-18+-C1 5h-32-B,, biologi,cal studies biological studies 57=55r6,, biological studies studi!es 6U-OlJ'-4, biological, studies 60-57-1 studies, 64-17-5, biological studies 67-56-1, biological studies biological studies biological studies biol~ogp:cal, studies biological studies 1,07-18-6, biologi~cal 67-63-g, biological studies 67-64-1, 67-68-5, biological studies 70-18-8, 71-36-3, biological' studies 71-41'--0,, 75-56-9, biological studies 77-78-1 78-83-1i, 143-90'-2 1i+?6-42-3„ biologicali studies studies 1n8-88-3, biological studies 108-95- 2, biological studies 141-43-5,, biological studies 151--1'-3, biological studies 309-00-2 4Ct4-86-4 461-78+-9' 504-63-2 525-66-6 594-27-4' 595-90-4 597-64-8 683*-18-1' 994-31,-U 1,Ci66r45-1! 1310-73-2, biollogd.cal studies 1461-22-9 1461-25-2 2270-40-8: 6673-35-4 7173-51-5 7v11i-3«-0 7446-7h-v, biological studies 7487-94-7, biological studies: 7733-02-0 7772-99-8, biol'ogical, studies 7778-50-9 9005-64-5' 1'rl043-52-4, biological studies 10108-64-2 21I259-20-1 21645-54-2, biological studies. 25322-68-3 (cytotoxicity of, potential iirritati~on in relation to) =9
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ANSWER 2 . AN CA103(7)~:49259a; TI Release of histamine from rat peritoneal cell's in vitro, as an index AU CS LO SO SC DT CO of'irritation potential! Jacaruso,:Richard B.;, Earletta~„ Michael A.; Trombetta, Louis D. St., John's Univ. Carson, Steven; Jamaica, NY'„ USA J., Toxicol., Cutaneous Or_ul. Tox;i'col., +(1), 39-48 4rz (Toxicology), 3 JTOTDO IS 0731-3829' PY 1985. LA Eng AB Using mixedlrat peritoneal' ce11!s, includi'ng mast cells, a technique was developed'to assess the ability of'test materials to;cause histamine (I) C!51'-45-6I release., This release was detd'. fluorimetrically, and noted to be concn.-dependent. This allowed the test materials to be ranked in terms ofi their potential. An, order of potency was obsd. as follows: tlriethanolamine Yauryll sulfate CY39-96-87 > triethanolamine CI1!i-)2-71'-6] > propyliene glycol C57-55-67!, based upon detns, of'the llowest concn. causing significant I release:. Microscopic evidence supported the:observation that I release occurred to varying degree;dependiny,uponithe test materiali and its concn. These observations are in agreement wi!thiin vivo studies which have rated'the primary irritation potential of these materials. Moreover,, these findings agree with data assessing the efflects,ofl these materials upon membrane integrity of cultured rabbit corneal cell's. This similarity of' findings suggest that,these irritants may act as membrane or permeatoxins since alterations of' membrane permeabi!l,ity have been implicated in current mechanisms: explaining I release,firomimast cells. Thi~s method can be developed, into an~adjuvant or aliternati've to in viuo tests or irritancy potential. For diagram(s), see printed''CA Issue.. KWI chem irritation histamine release; mast cell hiistamine release irritation; peritoneal cell! histamine release i!rritati,on IT Mast cell (histamine release from peritoneal', as index of chem, irritation) IT Eye,, toxic chemical and physical damage <irritation, fromichems.,, histamine release from peri,toneal' cells as index o+F). IT Sk!i~n, to>:kc chemicaL and physical damage (,i,rritation,, from chems., histamine release from peritoneal mast cells as index of) IT 57-55-6, biological studi!es; 1Ci^--7Y-6, bi'ological' studies 139-96-8 (dermal' and ocular irritatron fi^-om, histamine rel,ease frem peritoneal' cells as index of) IT 51-45--6,, biological studiies. (release of, from peri'toneal mast cellls, as i,ndtx of irritation potential of chems.Y 88749i1 3"71 40
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G i ANSWER' 3 AN CA103(3);:17886m; TI Ln vitro cytoto}:i'city assays. F•otential alternatives to the Drai!ze ocular allergy test AU Borenfreund, EI1en;, Aorrero,, Olina CS' L'ab. Anim. Res. Cent., Rockefeller Wniv. LO New York, NY 10021, USA SO, Cell Biol. Toxicol., 1(1), 55-65. SC 4-1 (Toxicol'ogy) DT J. CO CDTOE2 IS 0742-2091 PY 1984 LA Eng AP A short-term cytotoxicity assay carriledlout in multi~well test plates and a supplementary colony-forming,assay are both useful for screening and range finding of toxic concns. of' test agents. The highest tolerated dose (WTD), a concn. at whichionly minimal morphol. changes were obsd., was designated as endpoiint,in the assay. Epithelial rabbit corneal celils, murine,fibroblasts, Chinese hamster lung cells, human hepatoma cellis, and mouse macrophage cultures were used as targets. Several of the al'cs, tested at HTD in the colony-forming assay inhibited colony formation., A median ED,of colony formation was used as a quant. corroboratimg,test. The ranking of 34 to:ci~cants was virtually the same with all cell types examd. This easiliy reproducibl'e, rapid in vitro test is cost-effective and can be usedlfior preliminary large scale screeningi of potential toxicants. k(W chem cytotoxicity assay; mammalian celil chem cytotoxi!city test IT Macrophage. (chems. toxicity to, Drai-<e ocul!ar allergy test alternative in, relation to) IT Surfactants Alcohols, biiologi~cal studies (cytotoxilcity of,, to mammalian cell cultures, Draize ocular allergy test alternative in relation to)' IT Fibroblast (v•Tv„ chems. toxicity to,, Draize ocular aliergy test al,ts•rna.tilve, in relatiion to) I',T! Animal cell (V'-79, chems. toxicity to, Dra,ize ocular all'ergy test alternative in relatilon, to) IT 0uat'ernary ammonium, r_ompounds„ biological Studi'es (a11.y1benzyIdimet;-ryi, chlorides, cytotoxicity of, tomanmalian cell cultures, Draize ocular allergy test a1!ternntive in relation to) IT To>:iicity (cyto--, o'r chems., to mammalian cell'„ D)-aize ccullar allergv tlest alternative i!n rnl'ation, toJ IT Liver,, neoplasm (hepatoma L`2, flromichems. „ Drai: e ocular a11 erg',; test aI ternati,ve in relation to)', 8749i1372 41
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IT 57-55-6, bi'ologiaaI studies 64-17-5y biol;ogi'caL studies 67-56-1, biological studies 67-6'-O, biological studies 67-68-5, biological studies 7Y-36-•3, bioi;ogiicaS studies 71-41-0, biological studies 76-nu-9,, biological studies 78-9T-',„ biological studies 97-99-4 100-79-81 10T-1'8-b, biological studies 107-21-1, biological studies 1iU7-87-9' 111-'~7=-~, biological studies 111-70-6, 111-87-5, biological studies 123-39-7 119-96-B' 151-21 3, biological studies h 72'74-8 7681-52-9 7761-88-8, biological studies 9002-92-0 9005-65-6 9005-66-7 9005--67-8 1449c.. 68-: 756U?l 36-O 84136 4t-'S (cy!totoxicilty ofl„ to mammalian celd cultures, Draize ocular allergy test alternative in r-ellation t'o) 42
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ANSWER 4 i i AN CA102(9):73694p~ TI1 The safety of" propylene,gl'ycol and other humectants AU! Motoyoshi, Katsuhiro; Nozawa, Susumu; Yoshiimura, Masaaki; Matsuda, Kaz Lao CS Sch. Med., Niligkzta Uni'vr. LO! Nii'gata, Japan SD Cosmet. Toiletries, 99(114),,8v-9'1 SC' 4-3 (Toxicology) SX 62 DT J CO CTOIDG IS 0361-4387 F'Y 1984 LA Eng Ab When applied for 48 h to rabbit, guinea pig, mini,ature pig, and human skin by open and closedlpatch tests propylene,gllycol C57-55r67, andl other humectants C 1, 3-butaned i oI [107-88--r70 , pyrrol i donecarboxyliatrP, C98-79-3], and polyethylene glycol 2p01(F`EG 24U) C25v22-68-37?7 develloped no irrigationiin any of' species except humans, in.which case the compds. caused irrigation in the closed patch test only!. KW, propylene glycol skin irritation; humectant skin irritati'.oni IT Humectants (skin irritation from, in humans and lab. animals) IT Skin, toxi''a chemical and physical: damage (irritati'on, from propylene glycol and other humectants, in humans and lab. animals). IT 57-55-6, biological studies 98-79-3 1C17-BQ-U 25322-68-3 (skin irritation by, in humans andllab. animals, in closed patch test) ' IT 50-70-4, biological studies 56-81-5, biological studies 111-90-0 16277-71-7 25,265r71!-81 59113-36-9, (skin response,to,,in humans, in cIose& patch tests): 'f _
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ANSWER 5 AN CA101(17Y::145493b TI Skin irritancy flrom propyl'ene gl'yco11 AU WahSberg, J. E.; Nilsson, G. CS' Dep:. Oacup. DermatoT., Karolinska Hosp. LLO, Stockholm, Swed. SO Acta,Derm.-Venereol_, 64(4), 2S6-9D SC 4'-3 (Toxicology) DT J CO ADVEA4' IS OoO11-5555 . PY 1984 LA Eng', AB Two sensitive methods for the assessment of' skin,irri'tancy reacti,ons to propylene glycol (PG) C57-55-67 were used: laser Doppler 4"1'owmetry in man for erythema andlski'n fold thickness measurements in mam, guinea pigs„ and'rabbits for edema. Single (open and occiusi'veY andlrepeated (open) exposures were used. Trafuril was used as a pos. control flor the flowmetri'c',studies., In man, an increased bloodlfl'ow was,recorded' oniiy when PS was applied under occl'usionw A signilficant increase iniskin,foSd thi'ckness,was obsd. from day 7 in'the guinea pi'gl, but not in man (daily'exposures,for 3,6 days). Thus, occlusion i~s a,crucial factor and skin fold thickness measurements in guinea pigs and rabbits is a useful, complementary method for the ddtection and prediction of marginal irritants. KW propyl!ene glycoli skin irritati,on IT Skin,,toxic chemical and physical damage (irritation, from propylene glycol,, in humans,and lab., animals,, methods for assessment of) IT 57-55-6, biological studies (skin irritation flromy in humans and lab. animals, methods flor assessment ofl) 44
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ANSWER 6 AN CA99(75):11'6445s TI' Skin irritation by topical drugs AU CS LO SO SC SX DT CO Zesch, A. Hautkllini., Freien Uniiv. Berlin„ Fed. R(ep. Ger. Dermatosen Beruf Umwelt, 1(3), 4-8' 1-12'(F'harmacology) 63 J DBUMDB I S 0341-2432 PY 1983 LA Eng AB' It was shown in both healthy volunteers andlpatients with a history of contact dermatitis that propylene,glycol Ci57-55-67, a compd. often used as aniauxi!liary agent for' improving, the dellivery of topicaS drugs,, causes skin irritation in a concn.-d'ependent manner. The problems of' auxildary agents as they relate to skin permeabillity„ drug d'eliveryy, andlsk.in irri'tation are discussed. KW, topical drug skin irritation IT Pharmaceuticals (auxiliary agents for topical dellivery of, in humans, sk.in, irritation i.r.t.)', IT Toxicity (from auxiliary agents for topical, dellivery of' dtugs, in humans,, skin irritation i.r.t.) IT 57-55-6, biological studies (skin irritation flrom, in, humans, auxilli'ary agents ini topical dNug, delivery i,.r.t.) 45
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ArysWER,7 ANI CA98(24)t 204226m TI Alcohol-containing oral hygiene solutions CS', LO F'I Matsui, Tokio Japan, Jpn. Kokai Tokkyo Koho JF 58/3962n A2 C8ti/396207, 8:Mar 198:3', 11 pp. A'I' Appl. 81/139274, 3 Sep 1981 CL A61K31I/D45, A23Ce3/3G,, A61K7/16,, A61K7/22, A6'1'K31:/1'95, A61K.ti1/215 SC 62-7 (Essential Oils and Cosmetics) SX', 63. DT P' CO JKXXAF PY1,981 LA Japan AB Nonirritating oral' hygiene solns, are prepd. These prepns. contain ethanol C64-117-5] as a microbicidal agent and additives suchias propyllene glycol C57-55r6], amino acids, benzyl benaoate C12U-51-4]',., and polyhydric aics.. KW mouthwash aIc amino acid polyol' I!T Mouthwashes. (alic.-contg., mucosa irritation prevention in) IT Amino acids „ biological, studies Fatty acids,,biological studies. (mouthwashes contg. ethanol and, irritatiion preerention in relat'ion, to )', IT 56-40-6, biological studies 56-41-7„ bi:ologi'cali studies 56-84-8,, bnol'og0.caI studies 56-86-0, biologi~cal studies 57-48=7',, biological studies 57-55-6, biollogicaS studies 6-91-2, biological studies 71-()0-1, biologiical studies 71-23-£3, bio3:og,icai-studies 74~79-3, biological studies 107-21i-1,, biological studies 1i47-88-O 120-51-4 25322-68--- 25496-72-4i (mouthwashes contg~ , ethanol, and, ilrritati'on prevention im reliation to) IT 64-17-5, bi'ological studies (mouthwashes contg., irritatilon prevention in) 46
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ANSWER 8: AN CA98:(21):1741,94e TI Evaluation of the ocular-irritation potential ofl 56 compounds AU Guil!Iot, J. P.; Gonnet, J. F.; Clement, C.; Cai1''Iard,, L.; Truhaut, R. CS' Serv. Tolerance Locale, Inst. Fr. To•r.icoli., LO L'Ar'bresle 69210, Fr. SO Food Chem., Toxicol-, 20(5),,,,;,73-82', SC 4-1 (Toxicology) S% 62 DT J CO FfiTOD7' IiS 0278-6915 Pv1982 LA Eng AB, The ocular irritancy of'56 chems., was tested in the rabbit eye,,, with and without rinsing„ using,methods proposedlby the Assocn. Francaisee de Nbrmalisation (AFNOR) in 1982 andlby the Organisation for Economic Cooperation and Development in 1979 for the testing of chems., and that published by French authorities,for the testing of cosmetics and t'oilietries. The results obtained were used!to establish the eitent to which the assessment of a chem.'s;irriitation potential was affected by the diflferences between the 3 protocols in respect of' the observation times prescribed, the inclusilon and timing of rinsing,, the no. of animals used, and the iinterpretation procedure. Conclusio ns were also drawn about the influence ofl the physs state,and pH of a material on its potential irritancy and about the level of' irritancy that necessitates the use of eye protectilon6 KW chem,eye irritation eval'uiation;, cosmetic eye irritation evaluation IT Lanolin Chemicals Saouriingi agents Hydrocarbon oils, F'etrolieum spirits Siloxanes andlSil'icones, biological studi'~es. (eye irritation from, evalluation of')'. IT Eye, toxic chemical and physical damage (irritation, from chems.,,evaluatlion of), IT 57-.°-r5-6, bilological studies 59-'3-6 60, 87-7' 6<3-117-5, bioliogicai studies 72--17-3 77-78-11 91' 84-9 95-55-6 97-77-8 1!n8-1'6r7 148-88'-.T_•, biological studies 12Ci-92'-3 1'27- 30-8 1'30-8,a.,-8 144-62-7, biological studies 1!48-53--8: 156- 41-41 494-19--9 629-0:?.-8 996-11i-6 1C404 74- 6 1115--7i7-41 2001-94-7 2o5r]-46-6 253C>*-83-8 2736-2'•-4 274'-'8-6 3546-(A"-0 ?689-50-7 -'74Cr--18-9' 3861-99-2 76.:1-86-9,, biological, studies 10402-29-6 1347.=-90- 0 14'221I-4'7-7 16893-85-9 23z49-66-2 27691,-62'-9 26140-9'-4 '3974-68-4 41672-81-5 57267-78r41 701124-66-2' 8552u-32-7 8J5"-S-1'"8 85532-99-6 £:5 1-00-2 ' 85 + 3'- i} q-....' (eye irritation from, evaluation of) OD ~ N w' 4 , GD ' 47
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ANSWER 9' AN CA98:( 21 )I : :174193d I TI Evaluation of the cutaneous-irritation potential of 56 compounds AU Guilloty J. P.;:Gonnet, J. F.; Clement, C.; Caillard„ L.; Truhaut, R. CS' Serv. Tloierance Locale, Inst. Fr. Toxicol. LO L'Arbreslie 69210, Fr. SO Food Chem6Toxicol.,, 20(5),,, 563-72'. SC 4-1 (Toxicology) S%' 62 DT J' CO FCTOD7 IS 0278-6915~ PY 1982 LA Eng AB The primary cutaneous irritation of 56 chems, was tested in the rabbit using the method publi!shed by the French authorities for the testing of'cosmeti:cs and toiletries and the:methods proposed for the testing of chems. by the Assocn. Francaise de Normalisation (AFNOR) and, in 1979, by the Organisat'i'on for Economic Cooperation and' Development. The results of'the 3 sets of tests were compared and the effects of' differences in procedure andl nos. of" animalls were studied, together with the,possible relation between irritancy and' the pH of the test material,. The AFNOR protocol best met the requirements for such tests andlthat gloves should be worn for the handIi'ng,ofl all substances classified as moderately or severely irritant on,that,scale. KW chem, skin irritation evaluation; cosmetic skin irriitation evaluation IT Lanolin Chemicals Scouri'.ngl agents Hydrocarbon oils Petrol'eum,spirits Siloxanes and'Sillicones,, biological studies. IT (skiniirritation fromy evaluationiof ) Skin, toxic chemical and physical damage (irritation, from chems., evaluation of)' IT 57-55-6, biological studies 59-"'3-6 60-87-7' 64-17-5, biologi'cal' studies 72-1'7-u 77-78-1 91-84r-9 95--55-6 97-77-8 SIn8-16-7 1,fj8-88-3, biological stu.dies 12U--92-" 123r:<i-8 113fJ-85-& 144-62-7',,biological stu.dies 14'8 -'-8 156-43-4 494-19, 9 1 15-70-4 2001-94-7 2Q5a>-46-6 629-i_r?:-8' 996-31-6 1(?il4'-74-6 1 2.736 23-4 274 -38-6 3546U?'-« 3689-5p; 7 ,'7ap--18-9 '.861-99, 2I 76'1-86-9, biologilca.1 studies 10402-29-6 134'7?-90-0 ' 1422'1-47' -7 11689'-85-9' .';•7.49-86-2' 27f.91!-6::-9 2£3140 -9:'-4 '8974-68-4 4167'2-81--5 57 67-7~3-4 701''4-66 28.°.,528-1!2r-7 ' 85528-1'-8' (~ 855-_L-99-6. 85J 7-0l)--2. '. 854 , '•-1/1 (skin i'rcriitation f'rom, ev;aluation of'): ~ ~. ~ 48
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ANSWER 10 AN CA98'd14J':111-521n TI An in vitro~test for the assessment of eye irritancy in consumer products - preliminary fli'ndings AU York,, M.,;, Lawrence, R. S'.; Gibson, G. B'. CS Environ. Saf. Lab., Unillever FRes. LO' Sharnbrook/Fedford MK44' SLQ, UK SO Int. J. Cosmet. Sci., 4(6), 221-.:4 SC 62-3 (Essential Oils and Cosmetics) SX 41, 63 DT J' CO IJCMDW IS 0142-5463 PY 1982 LA Eng AB An in vitro method for the preliminary screening of'a no. of chems. reported in literature to have different eye irritation potential is describedL The validity of' this method was also investigated for assessing shampoo irritancy. The substances that produced the mostt damage to the cornea, NaOH, HCHO C5Ct-00-0] and Ac20 C1,Q8-24~-77, did not produce the most swelling. Max. swelling was seen with substances such as ally1, al'c. C1i07-1,8-6T, and FfuOHI C71'-36-31 which exertedltheir effects on the epithelium. The effect of pH on the irritant potential was investigated in a no. of', NaOH solns. (pH 11.5 to 14'.0) at contact times of' 10 s,, and 1„ 2 and 5 min., Followingg contact time,ofl 10 s aIl solns. with a pH .gtoreq.13.b caused significant cornBaL swelling. As the contact tiime,increased the threshhold for the prodn. of significant corneal swelli'rngifalSs. An adul't,shampoolwas tested undild. and at a concn. of 10% using contact ti,mes, of 10 and U0s, 2 andl 5 min. Following the 5 min contact times the undil'di, product caused opacification ofl the epitheliumiand some corneal swelling. The 10% soln, caused corneal swelling and loss of' epi~thelium fbllowingial'l except the 10 s contact,period. Thus, the in vitro eys test is,a valid model f or use as a screening procedure for strong irritants and shows good correlation with in vivo resu.lits. }:WI eye irritant chem; shampoo eye irritant IT Shampoos, (eye irritation from, in vitro evaluiati,on of')', IT Eye,, to:cic chemical and physical damage (,i,rri'tation, from chems., and shampoos, in vitro evaluation of) IT 50-00-0, bilologilaaS studies 56-61-5, bilol,ogi'aal studies 57-55-6, biological studies 64-17--5, biological studies 67-64-1, biological studies 71, _6-•_,, biological studies 107-18-6, biological studies 108-24-7 108-83-3, biologilcal studies 1310-73-2, biological studies 5Z06-7Ci-5 (eye irritation from, in vitro evaluation of) ~ 4?'
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ANSWEf; 11 AN CA96 (1i4) : 1110 17C?v. TI', Pharmaceutical steroid composition AU Rergstroem, Karl Ove,, Ulmius„ J'an; WL=nngrern„ Bo Lennart Torbjoern CS Draco AB LO Swed. PI Eur. Pat. Appl,. EP' 42827 A2, 3Cr Dec 19B1, 13 pp. Designatedl Statess BE, DE, FR, GB, IT, LU, NL, SE' AI AppI. 81/850105, 10 Jun,1981;, SE AppS,. B0/4580„ 1i9 Jun 1980 , CL A61K;9/ 1s1, A61tt''1 /58 SC 63-6 (Pharmaceuticals) DT P CO EPXXDWi PY 1981 LA Eng i AB Topical, corticosteroid compns, whichiprodlace min. skin irritating effects, consist of multiple emulsion systems in which the continuouss phase is aq, and the primary disperse phase is an oil phase in which a hydrophil'ic phase contg. the steroid in satd'. sol!n, is dispersed. Solvents,, nL2-5y,by wt. of' the compn,, which are immiscible with the: oil phase, such as gllycols, are,used for dissolving the steroids. Thus, budesonide C51333-22-3]10.n25 g,was dissolved in propylene glycol C57-55r6] 2.5 g,at 7ry.degree.. This soLn. was added at 70.degree., to the oili phase contg. a mixt. of' petrolatum 21.25 and beeswax 1.25 g and miixed to yield a steroid soln. in oil emulsion. This emulsion was then added at 70,,degree. to a mixt. of' cetstearyl aSc. 3, cetomacrogal 1000 ' 2, and distd. H20 70 g, and mi:;ed to give aa multiple,emuPsi,on. After cooling to room temp., a soft white shiny KW IiT cream was obtained. corticosteroid emulsiion:gl'ycol Skin, disease or disorder (topical corticosteroid emulsions contg. glycols for decreasing irritation in treatment of'J IT G1'ycolis,, biol!ogical studies (topi'ca1 corticosteroi,d emulsions contg., for decreasir.c skin IT irri,tation), Cbrticosteroiids, bioloq_ica3: studies (topicall emul'.sions r_ontg. glycols and, for decrersinas4.in IT irritation) 57=55-6, biollogicaI studies 5£34-Cr.1--2 25--22-68-' (topi'ca1 corticrosteroid emulisions contg., for decreasine skin irritatiion) IT 50-23-7 67-7Z--2 76-25-5 2152-44-5 51Z (topicall emul'sions contg, irritationJ glycols and, For decreasing skin ~ IPA W m 50
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ANSWER 2. AN CA1 O3 (1 )! : 40n8b TiI; Smoking material AU White, Jackie Lee; Stowe,, Mary Evelyn, CS Reynolds, R., J'., Tobacco Co. LO USA PI Eur. F•at. Appli. EP: 135266 A2, 27' Mar 1985, 26' pp. Designatedl States; BE, CH, DE, FR„ GB, IT,, LI, NL AI' Appii. 84P3f,f4429, 28 Jun 1984;: US, Appl.: 525055, 22 Aug 1'983 CL A24B15/18A, A24B15/3UE SC 11i-7' (Plant Biochemistry) D T P' CO EPXXDW FY 1985 LA Eng AB A'compnA for use in tobacco smoking products and which is comprised of pyrolyzed tobacco plant materials, water-sol., polysaccharidts, humectant „ andlflauori'ng material, and a methodlfor prepg. smoking articles from this compn., are describedl. In an exampl'e, Burley tobacco stems were pyrolyzed, ground, combined with,pollysaccharide gums, converted iinto sheets, sprayed with propylene glyeoI, shredded„ bliended with com, cut tobacco, and made into cigarets., Cigarets made with 70 parts tobacco andl 3fj parts of' pyrolyzedl tobacco compn. yielded upon smoking 5.5 mg total particulate matter and 0.37 mg ni',cotine; those contg. 50-50 tobacco-pyrolyzed tobacco compn., yielded 41.1 and O'.22', resp.;: controls made of cut tobacco only yielded 7.2 and 0:53, resp. k:W IT' IT pyroIyzedl tobaccoismokingiproduct; polysacchar-ide tobacco product Tobacco products (compn4 contg. pyroiyzed'tobacco and polysaccharides for), Tobacco smoke andl smok.ingi (ni,cotine,i'n, from tobacco products contg. pyrolyzed tobacco and IT polysaccharides) Tobacco (pyrolysis of, for tobacco smoking products) '. IT IT Gums and Mucilages Pblysaccharides, biological studies (pyrol,yzed tobacco compn. contq., for tobacco,product manuf.) 56-81-5„ biological studies 57-55-6, biological studies (in pyrolyzed tobacco compn.) IT'~ 54-4' 1-5. (in smoke from cigarets contg. pyrolyzed tobacco-polysaccharide compn.) IT 9r=tOp-3i_I -<_1 9000-40-2 11' 1 34-66-2 IT (pyrolyzed tobacco compn. contg._ for tobacco,smoking product man!rf. ) 90041v2-41 9005-25-8D,, hydroxyethyl, and -Pr derius. OD ~ (pyrolyzed tobacco ._ompn. contlg. , for use im tobacco smoking ~ products manaf.J (D . ~ W. :.r j,
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ANSWEF' 3 AN CA190,(18) ;1Rbr?^8v. TI Measuring the regenerati'oniconditii'oniof hot-wire pyrolysis probes AU Falke, Feter; f*uhl, Christa;i E+ruelil,Fse, Ingrid CS VCEi-Synthesewerk Schwarzheide LO F`I Ger. Ger. Dem. Fep,. (East): DD 203637 ' Al, 26 Oct 119633, 5 pp., AI Appli. 236730, 14 .I'an 1982 CL Gn1N3,1/f18 SC 69-4 (Thermody,namics, Thermochemistry, and Thermali Properties) S X 37 DT P CO GffXXAB! R`l"' 1783 LA' G AB er A known amt., of polyglycol is dissolved inia known sol:vent. Thee solvent is evapd. andlthe polyglycol is pyrollytical'Iy decompd. The decompn. products passed into a column so that C2 Frydrocarbons (ethylene andiethane) can be sepd. The temp. of the probe can be detd. Thus 100 mg of a,pol,ygl'ycol made from ethylene o::ide-propylene, oxi'de, with a av. mol,. wt. of' :3r340--40 C-1U was, dissolved iin 5 mL CHC1 3. Approx. L' ,.mu.L,of this soln, was placed on a Pt probe. At 10C).degree. the solvent he.d' evapd. After further heating of the probey N(as,cnrrier gas)' was'used to transfer the decompn. products into a gas chromatog. coliumn (2m .times. s mm) f'illed with Parapak:: N at 8s?6degree.. The amts. of C2 hydroearbons thus detd, can be used to det. the temp. ofl pyrolysis. k:;W pyrolysis temp detn,hot wire probe; decompn thermal polyglycol, temp detn;, ethyl.ene propylene glycol thermali decomprn temp IT Thermal decomposition (detn. of temp, of, using hot-wire probe) IT Temperature (detn. of, of thermal' decompn., of polyglycols,,,usiing hot-wi;re probes) IT Gl,ycols, properties (thermali decompn. of, temp. de±,n. of) IiT 57-55-6, reactions (mi'xt. of, wiith ethyliene gl:ycol, in pyrolysis temp. detn.) IT 1rJ7•-21-1, reactions (miC:t. of, wiith, propylene glycol, in pyrollysis temp. detn_)
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ANSWER 5 AN CA1 OO ( 170 : 138433h TI Decomposition of'carbonate'esters of t,Z-diols. The'chemistry ofl 1,3~bifunctional, systems. XXVI AU Bartok, M.; Molnar, A'.;, Bartok-Bozoki, G'. CS Dep. Org. Chem.,,Jozsef Attila,Univ.. LO Szeged H-6720, Hung. SO' Acta Chim. Hung., 114(3-4), 375-9' SC 22-8 (Physical Organic Chemistry) DT J CO ACHUDC PV 1983 LA Eng AB The,decompne of cyclic carbonates I(ni= 0, 1), and II',, as well as MeCH(OH)'(CH2)rnOHi(n = 1,, 2) and Et2C(CH2OH)2, was examd. in the: presence of KOH, KCN, andlLiC1!. With a large excess of'KOH, I', and II are transformed into a1cs. contg. one C less than their corresponding diols. Other reactions,, which are known, include flragmentation, to oxo compds., C02'elimination to give oxetanes, and fragmentation to olefins. For diagram(s), see printed CA'Issue. KW dioxacycloalkanedi,one pyrolysis mechanism; alkanediol pyrolysis mechanism IT 57-55-6, reacti,ons, 107-88-0 115-76-4 (pyrolysis of) IT 108-32-7 1 14'23-63T-7 17:361-58-9' (pyrolysis on„ mechanism of')' 5-

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