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_1OXuJNJ E PROG: 1 AU AD TI SI SO AB Reed KW AU -Yal k:owsk:y SH Dep. Pharm. Sci., Univ. Arizona, Tucson Lysis of human red cosolvents CA/102/214502P J. Parenter. Sci. CBAC COPYRIGHT: which enable the of lysis in i.m. blood cells in the presence of various Technol.; VOL 39, ISS 2, 1985,64-8 CHEM ABS Two in vitro methods are presented evaluation of virtually any soln. for the prodn. and i.v. administration. These methods differ from the std. hemolytic method in that the red blood cells (RBCs) and ghosts, which remain after mixing test soln. with RBCs, are washed with normal saline. The intact RBCs are then lysed with water. Since the final measurement is always made in pure water, the effects of vehicle components on the absorbance or soly. of Hb are virtually eliminated. These methods were used to evaluate propylene glycol (F'G) C57-55-6], DM80 C67-68-5], EtOH C64-17-5], polyethylene glycol Ci5?22-68-T] 400 (PEG 40cj) , dimethyl acetamide (DMA) C127-19-5], and dimethyl isosorbide (DMI) E53r]6-85-4] or hemolytic potential in comparison to a ref. of 10% EtOH, 40% PG, and 50% water. Measured LD50 values for lysis of RBCs are expressed as total vol. percent of cosolvent in whol e b l ood . These val ues are: 39.5% DMI,37. 0'/. DMA, 30. 0'/. PEG 400, 21.2% EtOH, 10. 3% ref., 5.7% F'G, and 5.1% DMSO. 2 AU AD WAHLBERG JE Dep. Occupational Dermatology, Karolinska Sjukhuset, S-104 01 Stockholm, Swed. TI c; I Erythema-inducing effects of solvents following epicutaneous administration to man: Studied by laser Doppler flowmetry. HEEF'/85/02890 SO SCAND J WORK ENV I RON HEALTH; 10 (3). 1984. 159-162. A Ei HEEP COPYRIGHT: BIOL ABS. Skin exposure to solvents can cause erythema, edema, scaling, and, eventually, irritant contact dermatitis. The irritant potential of chemicals is usually assessed by visual scoring, but in recent years a more objective measuring technique, laser Doppler flowmetry (LDF), has been introduced for the assessment of erythema. The method is noninvasive and allows continuous recording. In the present study 11 solvents were applied •for : 5 min to the volar forearms of a man and the kinetics of the response is shown. For 7 solvents (dimethyl sulfo:;ide, trichloroethylene, n-hexane, C C14, toluene, 1,1,1--tr-ichloroethane, 1,1,2-trichloroethane) an increase was Tound over the pretreatment values, whereas 4 solvents (methyl ethyl k:etone, ethanol, propylene glycol, distilled water) did not influenc e blood flow. The findings are discussed in relation to the macroscopic picture (whitening and erythema) and in relation to pr-evi ous stud i es of the edema-i nduc i ng e f f ects of the same solvents on man and experimental animals. LDF is well worth trying in cases of marginal irritancy and for predictive testing,; 1 since it seems to be more sensitive and reliable than the naked a?ye, I. 88698260

A U AU AU A Ll AU AD TI SI SO LA AB Mi11er F:R Hermann EA Young JT Landry TD Calhoun LL To:;icol. Res. Lab., Dow Chem. U.S.A., Midland Ethylene glycol monomethyl ether and propylene glycol monomethyl ether: metabolism, disposition, and subchronic inhalation toxicity studies CA/ 1<=r2./019045G? EHP, Environ. Health Perspect.q VOL 57 „ 1984,233-9 ENG CBAC COPYRIGHT: CHEM ABS Short-term and subchronic vapor inhalation studies in rats and rabbits showed that there are pronounced differences in the to:<icol. properties of ethylene glycol monomethyl ether (EGME) C109-86-4] and propylene glycol monomethyl ether (PGME) C132V-67-S]. Overexposure to EGME resulted in adverse effects on testes, bone marrow and lymphoid tissues in lab. animals. PGME does not affect these tissues, and' instead, overexposure to PGME was assocd. with increases in liver wt. and central nervous system depression. EGME is primarily oxidized to methoxyacetic acid C625-45-63 in male rats, whereas ' F'GME apparently undergoes O-demethylation to propylene glycol C57-55-6). Since methoxyacetic acid has been shown to have the same spectrum of toxicity as EGME in male rats, the obsd. differences in the toxicol. properties of EGME and PGME are thought to be due to the fact that the 2 materials are biotransformed via different routes to different types of metabol i tes.

4 AU AU AU AU AU AD TI SI SO LA AB M i l l e r- F; Ft Hermann EA Young JT Calhoun LL k::ast 1 PE Toxicol. Res. Lab., Dow Chem. USA, Midland Propylene glycol monomethyl ether acetate (PGMEA) metabolism, disposition, and short-term vapor inhalation toxicity studies CA/ 1 01 /205504J To;;icol. Appl. F'harmacol.; VOL 75, ISS 3, 1984,521-30 ENG CBAC COF'YRIGHT: CHEM ABS Male rats were given a single oral dose of . apprx. 8. 7 mmol /kg of 1-14C-l abel ed PGMEA C 1r?8-65-6] or exposed to 3000 ppm C1-14C7F'GMEA for 6 h. After dosing, expired air, excreta, and tissues were analyzed for 14C activity, and metabol i tes i n ur-i ne were i sol ated and i denti f i ed. Appro;:. 64% of the administered 14C activity was eliminated as 14C82 and .appr;:.24% was excreted in urine within 48 h after a single oral dose of radiolabeled F'GMEA. Similarly, 5=% was eliminated as 14CD21 and 26% was excreted in urine within 48 h after the inhalation exposure. Propylene glycol C57-55-67, propylene glycol monomethyl ether (F'GME) C1:'20-67-87, and the PGME sulfate C85684-i2-67 and F'GME glucuronide- C85684-23-7] were identified as urinary metabolites after oral dosing, as well as after inhalation exposure to F'GMEA. The urinary metabolite profile and disposition of C14C]F'GMEA were nearly identical to results previously obtained with PGME, indicating that PGMEA is rapidly and extensively hydrolyzed to F'GME in vivo. A short-term vapor inhalation toxicity study in which male and female rats and mice were exposed to i), 3cj(:), iocii_r, or 3000 ppm PGMEA confirmed that there were no su.bstanti_a1 differences in the systemic effects of PGMEA as compared to PGME. However, histopathol. examn. did reveal changes in the olfactory portions of the nasal mucosa of rats and mice exposed to PGMEA, which may be related to HOAc resulting from hydrolysis of F'GMEA in the nasal epithelium.

AU AD Wahlber-g JE Dep. Occup. Der-matol. , F~:arolinsE::a Hosp. , Stock:holm TI SI - Erythema-inducing effects of solvents following epicutaneous administration to man - studied by laser Doppler flowmetry CA/101/145366t`I SO - Scand. J. Work, Environ. Health; VOL 10, ISS 3, 1984,159-62 LA - ENG AB - CDAC COPYRIGHT: CHEM ABS The irritant potential of chems. is usually assessed by visual scaring, but the laser Doppler f lowmetry (LDF) was introduced for the assessment of erythema. The method is noninvasive and allows continuous recording. Eleven solvents were applied for .ltor-eq.5 min to the volar forearms of a man and the kinetics of the response is shown. For 7 solvents (DMSO C67-68--5], trichloroethylene C79-01-6], hexane C110-54-•3], CC14 C56-i3-5•l, toluene C108-88-3], 1,1,1-trichloroethane C71-55-6], 1,1,2-trichloroethane C79-00-5]), an increase was found over the pretreatment values, whereas 4 solvents (Me Et ketone C78-93-?], EtOH C64-17-5], propylene glycol C57-55-6], distd. water-) did not influence blood flow. The findings are discussed in relation to the macroscopic picture (whitening and erythema) and in relation to previous studies of the edema-inducing effects of the same solvents on man and exptl. animals. Thus, LDF is well worth trying in cases of marginal irritancy and for predictive testing,, since it seems to be more sensitive and reliable than the naked eye.

6 AU AU AU TI SI SO LA AB 7 AU AU AU AU AU AD TI SI s0 LA AB r-,ILE JD BEAVER JB FINK R THE EFFECT OF CHEMICAL CARRIERS ON AVIAN LC-50 TOXICITY TESTS HEEF'/84/06607 BULL ENVIRON CONTAM TOXICOL; 31 (2). 1983. 195-202. ENG HEEP COPYFt I GHT: Es I OL ABS. RRM QUA I L DUCk:: F'EST I C I DE FOOD CHA I Pd TOXIC SUBSTANCES CONTROL ACT USA Miller RR Hermann EA Langvardt PW Mcf;enna MJ Schwetz BA Toxicol. Res. Lab., Dow Chem. USA, Midland Comparative metabolism and disposition of ethylene glycol monomethyl ether and propylene glycol monomethyl ether in male rats CA/098/ 19L854 Z Toxicol. Appl. Pharmacol.; VOL 67, ISS 2, 1983,229-37 ENG CBAC COPYRIGHT: CHEM ABS ADDENDUM There were pronounced differences in the metab. and disposition of 14C-labeled ethylene glycol monomethyl ether (EGME) C109-86-4] or propylene glycol monomethyl ether (PGME) C1?20-67-8] by rats given a single oral dose (1 or 8.7 mmol/k:g). Approx. 50-60% of the administered 14C was excreted in urine, and .appr:;.12% was eliminated as 14CO2 within 48 h of administration of EGME. For F'GME, only 1(-)-"!:.0'/, of the administered 14C was excreted in urine, and 5()-60% was eliminated as 14C02 within 48 h. Methoxyacetic acid C6i5-40-67 Was the primary urinary metabolite of EGME', accounting for 8r>-9(-)'l% of the total 14C in urine. F'GME, propylene glycol (1,2-propanediol) C57-J5--6], and the sulfate and glucuronide conjugates of PGME were identified in urine of rats given PGME. Since methoxyacetic acid causes the same spectrum of toxicity aa EGME, it is likely that the adverse effects of EGME are the result of its metab. to metho:,yacetic acid. Differences in routes of metab. and types of metabolites appear to be the underlying basis for the marE::edly different toxicol. properties of EGME and PGME. i

8 AU -- M I LLEF Ftft AU - HERMANN EA AU - LANGVARDT FW AU - MCKENNA MJ AU - SCHWETZ BA AD -- Toxicology Research Lab., Health and Environmental Sciences USA, Dow Chem. USA, Midland, Mich. 48640. TI - Comparative metabolism and disposition of ethylene glycol monomethyl ether and propylene glycol monomethyl ether in male rats. SI - HEEF'/84/02620 SO - TOXICOL AFPL PHARMACOL; 67 (2). 1983. 229-237. LA - ENG AB - HEEP COF'YRIGHT: BIOL ABS. Male Fischer 344 rats were given a single oral dose of ' 1 or 8.7 mmol/kg of (14C)EGME (ethylene glycol monomethyl ether) or (14C)PGME (propylene glycol monamethyl ether). After dosing, expired air, excreta and tissues were analyzed for 14C, metabolites in urine were isolated and identified. There were pronounced differences in the metabolism and disposition of (14C)EGME and (14C)F'GME. Approximately 50 to 60'l% of the administered 14C was excreted in urine, and about 12% was eliminated as 14C02 within 48 h after a single oral dose of (14C)EGME. For F'GME, only 10 to t0'X of the administered 14C was excreted in urine, while 50 to 60% was eliminated as 14C02 within 48 h. Methoxyacetic acid was identified as the primary urinary metabolite of EGME, accounting for 80 to 90% of the total 14C in urine. PGME, propylene glycol(1,2-propanediol), and the sulfate and glucuronide conjugates of PGME were identified in urine of rats given F'GME. Since methoxyacetic acid causes the same spectrum of toxicity as EGME in male rats, the adverse effects of EGME are probably the result of its in vivo bioactivation to metho::yacetic acid. Hence, differences in routes of metabolism and types of metabolites appear to be the underlying basis for the remarkably different toxicologic properties of EGME and PGMt, respectively.

9 AU AU AU AD Gile JD Beaver JB Fink: F; Corvallis Environ. Res. ab., Environ. rot. Agency, Corvallis TI SI The effect of chemical CA/099/1oO5410 carriers on avian LC50 toxicity tests . SO Bull. Environ. Contam. Toxicol.; VOL 31, ISS 2, 1983,195-202 LA ENr AB CBAC COPYRIGHT: CHEM ABS The use of corn oil, propylene glycol C57-55-6], CM-cellulose C9()o4-32-4] and H20 as carriers of the pesticides carbofuran (I) C156~:;-66-21, dursban C2921-88-21 and endrin C72-2i_>-8] in dietary studies with bobwhite quails and mallard ducks showed that carriers had an effect an median lethal concn. (LC50) val!ies since dose-response curves changed with different carriers. With few exceptions, groups of birds presented with corn oil consumed less food than those presented wi th the other 3 carri ers, but growth was not af f ected by redd iced consumption. Anal. of feed samples indicated no effect of any carrier on test chem. concns. in feed. 10 AU - Si ngh F'P AU - Junnarkar AY AU - Seshagirirao C AU - F::aushal R AU - Naidu MUR AU -- et al AD - Dept. of Pharmacol., Biol. Div., Res. Ctr., Indian Drugs and Pharmaceuticals Ltd., Balanagar Township, Hyderabad 500 037, India TI - Pharmacological study of propane-1,2-diol SI - IFA/83/()6()70 SO - Arzneim. Forsch.; VOL .=2 ISS 11 198L, P1443-1446, (REF 22) LA - ENG AB - IPA COPYRIGHT: ASHP Neurotoxicological effects of high concentrations (50-100%) of propylene glycol (propane-1,2-diol ) following IP or oral administration to a variety of animal species are discussed. It was suggested that concentrations of 10% or less be used when propylene glycol is employed as a solvent in pharmacological or toxicological investigations due to its potential for activity. .

11 AU - Parts L- AU - Conine DL AD - Dayton Lab., Monsanto Res. Cor-p., Dayton TI - Superior heat transfer fluids for solar heating and cooling applications. Results of acute oral toxicity determinations SI - CA/098/155979Y SO - Report; ISS MRC--DA-1096-Vol.1; Order No. DE8?0Cri758„ 1981,•'6 pp. LA - E{4G AB - CBAC COF'YFILF-iT: CHEM ABS Acute oral toxicity tests were conducted in rats with 22 heat transfer fluids used in solar collectors, including 3, fluids that had been used in collector installations for 1-3 yr. The Gosselin acute oral toxicity ratings of the fluids range from 1(practically nontoxic) to ' (moderately toxic); most fluids are rated 1. Accidental ingestion of LDs is not very probable in normal use. By Gosselin's rating system, undild. ethylene glycol C107-21-17-based fluids are classified as 2 (slightly toxic), whereas propylene glycol C57-55-67-based fluids are rated 1. The use of ethylene glycol- and propylene glycol-based fluids for i yr, and of an aliph. hydrocarbon type fluid for 3 yr, increase their acute toxicity significantly. did not 12 AU - Nelson EB -I-I - Method and composition for reducing the toxicity of acetaminophen SI - CA/096/091674U SO ~ - U.S. PATENT NO. 43o7O7L 12/22/81 (State University of New York, Research Foundation) LA - ENG AB - CBAC COPYRIGHT: CHEM ABS The to;: i ci ty of acetami nophen (I) C1U=-90-2] is decreased by oral, i.p., s.c., i.v. or i.m. administration of a mixt. of I and propylene glycol (II) C57-55-6] (Er. :--12 g/kg of body wt. ). The ratio of II to I is 0.'-4000: 1(by wt. ). Other pharmaceutical carriers or diluents can be used with this mixt. Thirty mL/kg of combined I, II and 0.9% saline soln. (I and II in various doses) were given by i.p. injection to white mice. The survival rate among 89 mice was 96'l% measured at 96 h after dosage (II-I ratio was 7.5e1). II does not seem to have a toxic effect and does not adversely affect the analgesic properties of I.

F'ROr: 1 AU - Ishidate MJ AU Sofuni T AU - Yoshi k:awa AU - Hayashi M AU - Nohmi T AU -- Sawada M AU - MatsuoE::a A AD - Bi ol . Saf. Res. Cent., Natl. Inst. Hyg. Sci., Tokyo TI - Primary mutagenicity screening of food additives currently used SI -- in Japan CA/101/209264N SO - Food Chem. To::icol.; VOL 22, I5S 8, 1984,62?-'6 LA - ENG AD - CBAC COPYRIGHT: CHEM ABS Mutagenicity food additive screening;Anise Food additive, mutagenicity screening of;Apple Ext., food additive, mutagenicity screening of;Beet Red pigment from, food additive, mutagenicity screening of;Caramel Food additive, mutagenicity screening of Color;Ceratonia siliqUa Food. additive, mutagenicity screening of;Chlorella Pigment from, food additive, mutagenicity screening of;Chlorophyllins Iron-sodium salt, food additive, mutagenicity screening of;Chlorophylls Food additive, mutagenicity screening of;Cocoa Pigment from, food additive, mutagenicity screening of;Coffee Ext., mutagenicity screening of;Cola Ext., mutagenicity screening of Genus;Food Additives, mutagenicity screening of;0ils Lime, mutagenicity screening of;Oils Sage, mutagenicity screening of;Oils Clove, mutagenicity screening of;Oils Cumin, mutagenicity screening of;Oils Lemon, mutagenicity screening of;Oils Onion, mutagenicity; screening of;0ils Thyme, mutagenicity screening of;0ils Nutmeg, mutagenicity screening of;Oils Orange, mutagenicity screening of;0ils Mustard, mutagenicity screening of;Oils Perilla, mutagenicity screening of;Oil=_a Coriander, mutagenicity screening of;0ils Spearmint, mutagenicity screening of;Oil•a Grapefruit, mutagenicity screening of;Oils Peppermint, mutagenicity screening ofv0ils Cinnamon bark, mutagenicity screening of;F'olyphosphoric acids Sodium, food additive, mutagenicity screening of;Resin acids and Rosin acids Esters, food additives contg., mutagenicity screening of;Siloxanes and Silicones Resins, food additive, mutagenicity screening of

2 AU AU AU AD - TONG C - TELANG S - WILLIAMS GM - American Health Foundation, Naylor Dana Inst. Dis. Prevention, Valhalla, NY 10595, USA. TI - Differences in responses of 4 adult rat-liver epithelial cell lines to a spectrum of chemical mutagens. SI - HEEF/84/095b8 SO - MUTAT RES; 130 (1). 1984. 53-62. LA - ENG AD - HEEP COPYRIGHT: BIOL ABS. An assay for mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in adult rat-liver epithelial cell cultures (ARL) was developed to take advantage of the capacity of this cell type to metabolically activate promutagens/procarcinogens. A survey of the effect of 5 types of activation-dependent mutagens/carcinogens (mycoto;;in, aminoazo dye, polycyclic aromatic hydrocarbon, nitrosamine, aromatic amines and amides) on 4 ARL lines (ARL-6, ARL-14, ARL-18, ARL-19) indicates that the ARL/HGFRT mutagenesis assay with the 4 target cell lines is able to detect a spectrum of activation-dependent carcinogens. Individual ARL lines, however, responded quite differently to a given carcinogen. The ARL/HGPRT mutagenesis assay system thus offers distinct possibilities for the study of the control of chemical biotransformation processes.' In light of the specificity of the various cell lines to respond to a particular class of mutagens under the current assay condition, this particular assay system cannot be readily applied, to routine screening of suspected environmental mutagens of unknown requirements for- metabolic activation. For agents with a structure related to •those activated by a specific line, this system can be used to study mutagenesis resulting from intact cellular metabolism. 3 AU - Taylor SL AU - Berg CM AU - Shoptaugh NH AU - Traisman E AD - Food Res. Inst., Univ. Wisconsin, Madison TI - Mutagen formation in deep-fat fried foods as a function of frying conditions SI - CA/<_r98 /1 592 16Er SO - JAOCS, J. Am. Oil Chem. Soc.; VOL 60, ISS 3, 198=,57h-8{? LA - ENG AF - CBAC COPYFtIGHT: CHEM AF,S Mutagen frying potato fish onion Oil mutagen food frying;Cooking Mutagen formation in foods during, frying conditions effect on Frying;Cottonseed oil Frying oil contg., mutagen formation in food fried in;Fish Mutagenic activity of fried, frying conditions effect on;Mutagens Formation of, in fried foods, frying conditions effect on,Onion Mutagenic activity of fried, frying conditions effect on;Potato Mutagenic activity of fried, frying conditions effect on;Tallow Frying oil contg., mutagen f ormation in f ood fried in 88"8269 11