Tobacco Documents Online

r__ • o FILE 46D. lO. The revieg rece£ved from the British Industrial. ]l£olo$£cal ltasesrch ~sociaC£on (BIBitA) covers hoch short-tern and leas-tern tox£col~sy in • nunber of an£nal spec£ea and also £n man. I have rev£eved the BXBR~ evidence and bel£eve chat'parcs of it are open co £nterprecacion. ~£ul S:.ud£es Zu Cho anlaal studies, for exaaple, exposure by the oral and i~h~ion roucu lppurJ co present no l~r:inular problm uncll (pass 6) equivocal results •re uoced In relac£ou co ueuroual oedeua, auphysmw and lun8 oedena. Pulmonary lr~£cac~ou, couf|esctou and haelorrhsse have also been reported follou~nS shorn (2 - 24 hour) exposures Co h£jh levels of 7coon 11. l~c is •leo uoced chac these effects v8~7 w£dely beCeeen species. S|.u:Llarly, epec£es dependent, effects on heart rats, hypoceuslou and ~ard£•c ar~hy~hsLt• are noted £~ re~aciou Co the card£ovancu3.ar system. The rev£ma £ndicaces, ~vlch a reasonable desree of cou~£deuce, ~hat chore ~.s no defin£cLve ev£dsnce which would sue•eat chat l~reou II £s cazc£uoseulcj v£a the ora~. or £nhalst£on routes of adm£n£strattou. The uuCtgsnlc scud£es are also neSaC£ve or equ£vocal and a siqlt reproduct£on study tnd£cated chat there ~tre no s£su£f£cant effects. ltu ,uu St ud£ea In contrast Co the antml studies 1c ls consLdered chac the resp£racory and card£oveacular evLdence from humus lives r£se for cons£dereble concern althoueh ch£s is not reflected stronsly £n the BIBRA revlev. For example, on pele 9, the reviewer stares chac no ser£ous e~ects were seen on the E~G of 10 subjects exposed co TCI~I for ~ or 45 seconds. Nevertheless the reviewer notes (pale 9) "most of the sub~eccs developed respiratory s£nus arrhycbm£a and bradycard£a and each exh£bltsd a byphas£c reduction £n max£nun exp£raco~y f~ow race (HEP). Follo~n8 a 60 second exposure there yes a transitory cachycardl• ~ch neKatlve T waves In 2 of the subjects". In the go~lmaln~ paragraph the rev£ever considers two other scud£ea. Theme lead essent£ally co the conclusion that, apart from a sl£Ehc decline iu coguat£ve funcc£on, Chore are no untoward effects on the heart, ~unK or nervous system. 2eeeoeeee 0 0

-2- these cwo references are ¢rJ.C£cal Co the ~uisessnmnc of the hunsn dar~, ~ have exwlMd :he or£81nA1 papers In derail. The paper by LD.Scsvsrc ec al (1) vtd.eh concluded ctutc "none ot the subjects showed any decreunc in pulnou:7 function or alteration in esrd:l.a¢ rhythn" vu based on excellent aechodolosY and both shore and ~ tern exposure (8 hours) of 43 sale end 32 levels sub~eccs. Zn practice the studies specific Co Freon 11 (as dlstinct from those on cartslu |olvents) were for periods of l, 2 or 8 hours st non:LnA1 levels of 250, 500 or 1,000 ppa. Zn contrast the vo:k of Y.Val~.c or, el (2) ezaatned :he e~fects of short-tern exposures (15D 45 and 60 seconds) in 10 subjects. De:ailed ex.snl~sr.lon of lun8 funcc:Lon, i.e. ux:Laun expJ.rar.ory flow a: 25Z and 50X of vital cspsct~TD shoved thsr. chore wu 8 reduction bf be:veen 6Z to lOZ In vencllacory capeclty. These reductions were b/phasic occurrin$ after s leg nlnucu end suhoequsntly after 13 co 30 sluices. Yreou 11 had :he 8:eaces: effect of the aacerinls studied. klthoush Valtc reported chat there vu no serious c~rdtac effect, nose subjects developed respiratory sinus arrhyrAuLLa. Irady- c&rdla and Increased vsrLnbL1J~7 of bur: race occurred In :he "a:loricy of :he o:her 7 subjects. Val2c concluded :ha: "our scud~u s~ :hac beth respiratory and cardiac effects nay follow inhalation of ¥reous. ~t rosy re3.3, be that: chess effects are note serious in those who already have respiratory or card~.l[ disease". References (1) Sutuart. LD., Neuron, P.K., Barecca, E.D., Herruan, A.A.j ~orscer, n.Y. and Sore, I.J. Physiolosical response to aerosol propellants. Envtr. Rlth Perspec:. 26. 275-285, 1978 (2) ValLc, ¥., Sku=Lc, Z., Banclc, Z., Kmta~. H. end HeceJ, H. Effects of fluorocarbou propell&ncs on respiratory floe and ECG. Sr.J. lnd.Hed. ~ 130-136, 1977. 3eoeoeee0 o C) m

-3- Conclusi.mss b~t18~ I have no Srounds for refuels8 the revleu and appraisal nade by 91BRA, my considered view is chat ic van prepared as a balanced appraise1 in relation Co the industrial use of Frees particularly ec levels up to the threshold llnit value. Zn contrast we ere concerned rich the~se of Frmon In • roberts expansion process and the subsequent use of the processed tobacco in ciJarectes. submlc chat our prims need is co ~ouid~er the possible effects In circuascancesvhere: / (•) Lar|e numbers of mabJeccs ere exposed (b) The exposure is to low residual levels but is frequently repeated. (c) Those exposed are people of •11 eZes (16 upwards) in all states of health which irlll cert~Lnly include those erich pre-ex£sc£n8 pulmonary and he•re disease of any etiology (d) The exposure co 7teen is couplndvtth stmslcansous exposure to a very side ranis of ocher chemicals ghtch exist, mostly ac very or extremely low levelsw In cllarette snokc, W~ch chts backsround the continuous exposure of healthy subjects to relatively hizh levels of Frees 11 Is less appropriate than short-term exposure. On chic basis alone I consider chat the work of Valic ec el is more relevant than ~ha~ of Scevert ec el. IC should be noted further chaz the conclusions of Vslic are effectively reinforced by the observations in animals. As noted above the BI~RA appraisal (paSs 6) comments on • variety of bronchopulaonary effects In relation to Frees 11 In different species: these effects include respiratory functions pulaonary circulations bronchoconscriccion and dilation. S/JLtlirly, in relation Co the cardiovascular system the anlmal studies show Chac bradycard~a and cachycard£a occur In various specles whilst there ace numerous observations o~ ~nhaled Preen 11 causLns hypo- cens~on and cardiac arrhychtLas. Ic is also noted chac does and monkeys are particularly sensitive and susceptible co secondary ef£eccs such as coronary ischeemte and cardiac necrosis. /~emeooooe 0 Cr~

-4- s~ry' thereforej it is conceml4~:l rJuLC pr:Ln,e couider&rion ~t be siren to: the par:Lcular clrcunstuces of the ctssre::e £ndus:ry and :he s:r.acks vhlch are uutde aSatnsl: 1:: (2) :ht ~ h~t reported by Val£c ou hulchy subjects wh£ch £s supported and supl£fled by :he anise1 dare. Converse17, :he clara rela:ed co tadue:rlsl exposure of ldencLfLed, relac£vely snell mmbers of "hul:hy" subjects is re|staled as less teleran:. On :he besls of the evidence Z reeoansnd :ha: :he use of Freo:~ 11 £n =obscco produc:s should be phased ouc as quJ.ckly as prsc:ic&ble. GLvan s sacZsfaccory sl:eru:Zve, Z vould recouaend :be: rreon 11 should ~oc be =eesrded as an acceptable process residue a: any level~ S. IL.EVELTN O% tSA'l'~ -t~.....~n6 4AW AQU ~ U~s,A, tk 4AA/nu

Page 4 IICCI-BuI1e~in No 1/83 ° sulfide for shampoo and hair-grooming products and for products t~ control seborrhelc dermatitis. \ Comments on the "~dvance notice of proposed rule- making are due March 3, 1983. / °" I Copies o£ the notice are availa~l~ at IICCI (39 pages). / / COSMETIC INGREDIENTS , AUSTRIA /.o 2 -Am ino- 4 -hi trophenol .. (ANP), ". The percutaneous ah~rpt£on 0~ the hairdye constituent 2-~Jaino-4-nitrophehol (kNP) wa~studied by H Hofer, G W Schwach and Ch Fenzl at "Zn~ltut f~Biologie, ~sterreichischu Forschungscen~u~, Se£bersdorf, Austria. The absorptio.n from two formulatlans, one containing carboxymethy~cellulose as a thickening agent and the other c o'ntalnlng olelc acid and.. Isopropanol, was examined after application to rat skln. Absorption was foun~:to be greater from formulation two, which cgntained olelc acid and isopropanol. (Pub- lished £n Food and Chemical Toxicology, Dec 1982) 6.2.2. ~..-'" ~%- ~o- DENMARK Chlorof luorocarbons The Danish National Board of Environment Protection (MilJ~styrelsen) has published a proposal for the prohibition of the use of fully haloqenated chloro- fluorocarbons as propellants in aerosols. According to the proposal the prohibition would take effect by stages. Comments on the proposed prohibition were due by Jan I0, 1983. Propellants and solvents in aerosols A Draft regulation on the use of propellants and solvents in aerosol containers was issued by the Danish National Board of Environment Protection (MiljSstyrelsen) on Nov 15, 2982. Accordin~ to the Draft regulation the following propellants and solvents would be provisionally allowed for use in cosmetic aerosols: butane, l-chlor, l,l-dlfluorethan (F-142b) - limit 20t, chlor- difluormethan (F-22} - limit 20%, l,l-difluorethan (F-152a), dlmethylether, ethylacetat, heptan, iso- butane, octane, pentane and propane. Final decision regarding continued use or prohibition shall be made before Jan i, 1988. O O C~ -c~

o IlCCI-~ul~etln No 1/83 P.~e 5 Isopropanol would be permitted up to 15t in cosmetic aerosols, while the following propellant| and |olvents are proposed to be prohibited: aceton, butanols, butyl- acetates, cyclohexane, dlnitrogeneoxlde, 2-ethoxyethanol, ethylglycolacetate, hexane, methyleth¥1keton, propanol and xylene~ trlchlormonofluormethan (F-If), 1,2-dichlor, tetrafluorethan (F-114) and dlchlordifluoraethan (F-12). GREECE Chlorofluorocarbons The Greek State Drug Control Laboratory has infozmed the cosmetic industry association in Greece that the use of fluorocarbons as propellants An drug and cosmetic products has been reexamined. Referring to undesirable human effects and environmental effects of fluorocarbons, the Drug Con- trol Laboratory ks planning to prohibit the use of fluoro- carbons as propellants in cosmetic aerosols. The Greek cosmetic industry association has been asked for comments and is preparing objections to the proposed ban. Copies of the document issued by the Drug Control Labora- tory are available at IICCI _i_n_E_ngl__is_h_ (4 pages]. O c7~ tJ~ r~J tJ~

• % 2.~ 11. 8~ Official Journal of the Europe•n Commumties No L ~2Vl29 o COUNCIL DECISION of 15 No.tuber 1982 on the consoliclssion of precsuciomsry meMures concerning chiorofluorocmrbons in the environmen¢ (S~$1EEQ THE COUNCIL Of THE EUEOi~.AH COMMUNrFIlS. Having regard to the Treaty establishing the European Economic Community. and in i~'ticulu Ardcle 235 thet~.of. Having rejpud to the propoasi from the Commis- • ion (% Hgviq te/~d m the opinion of the European hdi- Mn~t (z), I-lavins ~ to the opinion of the Economic and Social Commirzee (% Whereas Council Decision 80/372/EEC of 26 ldMch IPll0 concerning ~ in the environ. mmc~ pm, ided ~ mo gm,,~ in pmduc~ cape- mgl • natuotion in the me of chlomlLuomcad~m F-I! and F-I2 in the filling of ammof cam; whenm dug Deci~on provided for • m-enmuudon of the mmugoa taken, in the li|ht of the av~dlable scientific and economic data: ,ion and tolvenu sectom should be limited ; m this end, appropriite action should be undemken : Vi~mas drain| the fire half of 1983 the measun~ to be token should be m-••mined in the tight of the sciendfic and economic data a~milable and such fumd~r masures as may prove necesnry in the light of this ~in~m should be adopted as soon as possible end not later than 31 December 1983 ; since the specific powers of ~-'tion required to ~lopc this Decision bey• not been provided for in the Trem7. it is neceas~'y m invoke ?ur~cle 23S HAS ADOPTED THIS DECISION: Artic~ I Member Smum droll udxe all uppmpri~ue hUm•urea to ensure th-, /ta~.Je i (I) of Decision 80/37Z/EEC is 8plAled on the Ixmis of ~ definition of pmducdon caimcity and the reference figure f~nn in the Annex. Vbereas thu re-mmmination hu shown that it is neceumry for the Community m continue m pursue • preventiv~ policy: M~qrmm the precaudomuy memmms dteldy ukett need to be mainlined and comoliduted ; Whenms Assicle 1 (l) of Decision 801372/EEC should be applied on (he be•is of • ixrecme gad hssmonized definition of she production cap•city of chlmofluom- cadxxu F-It and F-12; vhen~, on the bas~ of that definit~, the lpe0 loud pmductino cap~ty has been calcui~l for the Community m • whole; Whegeas, in prep•radon f~r periodic ~m of Community policy on the mb~'t, the Commission should collect 8nd compare appropriate gatisdcal information on the production and use of chlom- fluorocarbons ; Wherexs, as • precautionary memmre, the emissions of chlmofluorocarbons in the synthetic foam. refrigera- (1) OJ No C 2651. 11. 10. 1981. !)..5. ~JNo C 12.S. 17..5. 15182. p. 167. (') No C 348. 31. 12. 1tat. p. t~. (o) OJ No L 510, 3. 4. 1980, p. 4S. Artide 2 1. Member Sum shall ,.ake all •ppmprige meumu m k:ilimte the periodic cofk~on by the Commission of the tlq~mp6ate m6sticd infomution on ck production 8nd me of the chlomauorocarbom F-It •nd F-12. 2. Member States shall cooperate with the Commm- sion in act.ions 8imed st feducinI chlomfluomaubon losses and developing die ~ practicable technofogies in onief to limit emigiom in the synthetic foam. retri- gem•ion and tolvenm sectocs. Article J The measures taken in pursuance o/ Decision 801377./EEC and this Decision sh•ll be re.enmined. not later man 30 June 1953 in the light of the scim- tiGc and economic dam available. To this end. Member States shall, ~ to considerations of commercial confidentiality, provide the Commission with the msul~s of my study or research •v•il•ble to them. The Council shall adopt, as soon as possible and in any m 0 0 0", r~ C~

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° ~ . • s / a/46o-lo Note to Mr. N.E. Willis 1Sth Se.wtember 1982 FREO~ 11 b Changes in relation to Freon II were announced in the 1980 list of TLVs. The changes included in the 19R2 edition are as follows =- TWA C 1,000 pea C S,600 ~/m3 Note that the C indicates a ceiling limit; this is a new category in TLV values. ~here ~s no STP~ (Short Term Rxcurslon Limit) quoted for com nounds with a ceiling limit. The Library has run a ch~ on .~uropean Chemical ~ews over the last 6-9 months and could not pick up a news item on Preon II. At the same time as I made my request I also aske~ them to do s computer data base scan and I attach the relevant Drlnt-out. As you will sea, thereare references to carcinogeniclty, but these relate to "second order effects'. Ry this I mean that the ~rlme concern has been the effect of Freon on the under atmosphere, the subsequent increase in OV radiation leading to skin cancer. &s a second check X spoke to the Information Denartment of BXBRA and they referred to an item in the ~I~RA Bulletln for July 1981 which gave preliminary results (negative) from a long- term Inhalation study on ?reone 11 & 12 at levels up to 5,000 D~m. In addition, they mentioned that the only positive carclno- genlclty study that they were immediately aware of was a very old one, re~rted in "~ature", when FTeon I] and pioe.ronyl butoxlde were examined in combination. I hope this clarifies the position but, should Thsve misse~ anything, Z would be interested to know. Enc. S.R. EVELYn! C C O~ ~,,mmmA_ j ....... ~ m---- A~U ~ mm~_~a- ~m~