Document npzVzYazNMNYXNbaK1LzrzgOX

I .d * ' Ijjfcta I, .1 ft I <*. ft * v i *tf *'^ECEIVcr* '-; ::g 1990 IB TOXZCZTT Or VIHYL CHLOXXDC VXTOR A brief liMiry of tha Published Uttntort ftbraqr 7, 1*74 V The following articles and abstracts, compiled by Tha bow Chemical Company, arm believed to include most of the significant scientific information on the toxicology of vinyl chloride in nan and animals. She articles and abstracts are arranged in chronological order. Articles published in the last half of 1973 may not be included if they have not been __^abstracted by .Chemical Abstracts or biological Abstracts. " Important review articles which summarise snach ol the old literature have been used to cover the literature prior to 1961-1942. Therefore, copies of certain articler and abstracts described in these early reviews are not included in this compilation. Since, vinyl chloride (ehlsrosthsne, CH2CHC1) is a gas at room temperature and pressure, the common route of toxic exposure is by inhalation. As with many liguified 'gases, contact of the skin or eyes with escaping eospressed vinyl chloride can produce freeling and frostbite. (Torkelson etal, 1961). Vinyl chloride has long been considered to be very low in --toxicity by acute inhalation. Lehmann.and Vlury (1938) rixed the literature and reported work by Schauman chloride to be a candidate surgical anesthetic. Schauman reported little pathological changes even after repeated exposure to anesthetic concentrations. \ 22824001 4t )\ bFG22706 - T 2 V. F. van Oettingea (1SS) of the 0. S. Public Health Service stmnarised the available toxicity data on many halogenated hydrocarbons in an excellent aonograph. According to voa Oettingea, several.authors had reported vinyl chloride to be rapidly absorbed and axerated through the longs and to cause anesthesia, the following is on Oettingen's sunnary of the toxicity of vinyl chloride in aniaals and nans "As to the toxicity of vinyl chloride, Patty, That, and Waite (1930) studied this in guinea pigs, they found that exposure to 20 to 40 vol. percent kil^s the aniaals in a very short tine, that concentrations of 10 vol. percent are dangerous to life with exposures for 30 to <0 minutes, and- that 0.5 vol. percent is the maximum allowable concen tration for several hours' exposure without causing acute disturbances of severe nature. Aniaals exposed in this wa showed sons edeaa of the lungs and hyperenia of liver and kidneys. They considered vinyl chloride less harmful than chloroform or carbon tetrachloride and of a.siailar order of toxicity as ethyl chloride. Schanaann (1930) found that mice and rats tolerate repeated light narcosis for 4 hours daily on 5 to consecutive days and for 1 hour daily for 4 weeks without showing kidney or liver injuries. Dogs which had been narcotised for 3 hours with 10 vol. percent on 7 occasions in the course of severSI weeks showed no consider^) ansa Q>nni la klOaav and e4aKa rnmraiiH Hnma Z o o te & z z (19341 determined the vinyl chloride level-ia *$ blood ; - at the time of cardiac arrest as the time of respiratory arrest is 27 ti 3# 'mg percent, the sane value for chlorofosa being 50 to 79 ag percent. BFG22707 % vECtiVED ! irru Regarding tha toxicity of vinyl chloride for mant Patty, Yant, and Waito (1930) expressed tha opinion that tha gas does not possess adequate warning properties because of its odor or irritant action, but that it gives warning by producing symptoms of dlssiness and disorientation in advance of hars, except when present in exceedingly high concentrations which would cause almost ianediately help** lessness and unconsciousness. Inhalation of 2.5 percent' will soon cause dlssiness, disorientation, and a burning sensation in the soles of the feet, which synptoas disappear ianediately after discontinuation of the exposure except for a slight headache which nay last 30 minutes. These -authors suggested the use of vinyl chloride for narcosis in nan." As a result of two deaths in Canada, the acute inhalation toxicity of vinyl chloride was studied by Mastronatteo at al (1940) who reported that exposure of nice, rats, and guinea pigs to 10, 20, and 30 volune percent vinyl chloride caused the following mortality* NUMBER OP DEATHS IN DIFFERENT GROUPS OF FIVE MICE, RATS AND GUINEA PIGS EXPOSED FOR THIRTY MINUTES TO VARYING CONCENTRA TIONS OF VINYL CHLORIDE IN AIR Vinyl chloride concentration "(percent by volune in air) Mice Laboratory aninal Rats Guinea pigs Total ~ jp > V ' ' * /I , 1/5 W` ` jg S/I . m. i '- /IS 5/U v-- .V -'V- **? l / r l/ 11/lS 2/% - .- A delayed death occurred within 24 hours following exposure. 22824003 i BFG22708 1 I vEQiltVED Jg ^33C T. 4* # .* / Iom pulmanary hyprii and engorgement vu Observed by these investigators* bet liver and kidney.injury were ZMizkably low. Deaths were doe to narcosis. The first report of studies to determine the* effect of long-term repeated exposure (C snaths) were summarised fay Torkelsoo, Oyen and Rowe (19(1) as followsi ... ^Repeated exposures of laboratory' animals to several concen trations of vinyl chloride in air were conducted to determine % the' chronic toxicity of this material towards animals in order to assess the hasard to humans. Vinyl chloride was found to have a slx**ht capacity to cause liver and kidney * injury on repeated exposures. Male and female rats showed micropsthological 'changes after repeated daily 7-hour exposures at 500 ppm for 4.5 nonths. Repeated 7-hour exposures at 200 ppm for six months resulted in micropathological changes in the livers of rabbits and statistically significant increases v in the average weight of the livers of male and female rats -- ---but-no-detectable-changes-in-dogs and guinea pigs. Repeated 7-hour exposures at 100 ppm resulted in slight increases in the average weight of rat livers, the other speeies -- were not affected. -All species studied tolerated repeated daily 7-hour exposures to 50 ppm for six months with no *;' --detectable injury. """ Repeated-daily 1-hour-exposures -at 200 and 100 ppm of vinyl * chloride were without effect, longer exposure* capseda sligjtt^^H increase in lives weight. `w - 'ah t i \ j ! 22824004 BFG22709 4AUrmi* rtEC ElVED .:/ *:G 13S0 *. - i*V?-: tt* t44 for mlmt^i regular telly 7 M 0-hour (Xfotuni Ike defined aa*fch^eoccatratloe below vhlc& practieally' all analytical resolU musV tell. tec value of lMJna tt ti-"- <*., suggested as this standard for ri&yl chloride/wlth i HV'Jk: ****? average fo* all exposures act toexoaed * jgju 3* /> *? .* ' r -T-` ' '- j- ~ sC^ tester^ Greenberg, amd'Idaho (19431 tote strcog exception, te tec conclusion el Torfcelsen ct al (1941) that SO mb should be a m*ximqm tine weighted ayerage exposure for workers. On the basis of 3 months exposure ef rats to 2 . solum .percent and 19 dayg to 5 volume percent, they concluded that 500 ppn was acceptable as a TLV despite ninor changes which they observed in rat livers and which they considered "ware within the normal range an/, were not pathologic in nature.* Because of these conflicting reports, the TLV Committee of the ACGXH is 1953 chose to change their TX.V fro* 500 ppn as a naxleuw time-weighted average for industrial exposure .tg.500 ppm as a ceiling value. {American Conference . Governmental industrial Hygiene, 19531. tinea 1952, numrous Kuropean articles on vinyl chlorite have appeared, particularly in the tuaaien literature. Per several reasons, those articles are difficult in interpret ~ii terms of chronic toxicity alnee tbs reported exposures tn te mixtures w wore oteorwiae ill-defined, te* . l l1 'f ':-'V t. 1f* pi T 1 DECEIVED i':?'T=SD 'J a In 19(7, reports appeared in the literature describing a . conditiee known as acroosteelysis lit wozkaen engaged ia polymerisation of vinyl chloride toe polyviayl chloride. arris and Adaas (1967). reported on teCT cases ia Europe. Wilson et el (1967), reported on 37 cases ia the B. T. Goodrich Company. Basalaev (1970) described the use of large photof1uorography for diagnosis of aeroosteolysis ia isia. Basalaev et al (1972) described studies ia rats - rabbits and claimed to have produced the disease ia these species. Fethiere and Kerxner (1972) discussed the disease as did Jfihe et al of the University of Bonn (1973}. JQhe et al (1973). described a? syndrome consisting, of (arranged ia decreasing order of occurrence) thronbopenia, splenomegaly, liver damage, obstruction of ventillatioa, circulatory obstruction, and skin and bone alteration. -Am a-result of this problem, the University of Michigan in 1967 was retained by the Manufacturing Chemists Association to investigate this disease in sponsoring American companies. ) The results of a large scale epidemiological study of workers then currently employed in vinyl chloride and polyvinyl chloride production ware reported in three publications <r- --------by this group (Pinman -et al, (1971) Cook et al,- (1971) and fiodson et al, (1971)). Pinman et al summarized the study as follows > i epidemiological study was .performed covering S,0U ileyeos with 21^310 man-years experience is various phases . Od vinyl chlorideivc) and polyvinyl chloride-(fee) i feeturisg in 32 plsnts throeghoet the united States end yt v. /.Ujf'i..;- total number of definitive cifw ef scrooateolysis - *. - *- % 22834006 ) BFG22711 i n ngip|i|iOTg^^ T -DECEIVED' - , p ,; . .~L 1 ROD was 25; 1C othar individuals wars ondar suspicion. Shis condition is claarly associated with thf hand claaniag of polymerlsers. Morfcazs engaged in othar phases of PC or PVC manufacturing do aot appear to be at risk of developing hot. She importance of laynaud's phenomenon as a eon- '' eonitant of AOL is taphasised. Several ftatlstical approaches for rapid nedieal survey axe suggested. Aeroosteolysis appears to he a eysteaic rather than local disease. Presently, neither the etiological agant nor its portal of entry is known." Cook at al describes the* polyvinyl chloride production "process in consider Isle detail?--They concluded that although no etiological agent could be identified. "There appeared to he a correlation between the extent of.degassing prior to entry into the reactor" and the incidence of aeroosteolysis. Mutchler and Kramer presented a paper at the 19Ct Gordon Research Conference which was subsequently published (1972). which reported on "The Correlation of Clinical and Environawntal Measurements for Workers Exposed to Vinyl Chloride " The -authors drew the -following conclusioni *6ur' findings suggest that repeated exposure to vinyl chloride -at nth levels of 300 pp* or-above for e -working lifetine together with e very low level of vinylidene chloride nay .result la slight changes in certain physiologic and clinical laboratory parameters. The possibility of sons impairment.in &vef-function-testis-must be cenidexe^nvab.though ne overly clinical disease was evident in individuals "We shall continue our* study/b# tfwggaet that sloglar studief to halp clarify the oftMn notarial^ be iSfcrfomad for othar workar populations eJqpoiiWtt to vinyl chlori^o'alone." ... . "'*# 22824007 BFG22712 V Y % fp- i *. RECEIVED J-M '1290 < Aa m sponsored studies bp Pinsma et el sad Rtrtchler sad '**'4 Imer appear to' be tbe only two sifttlfieaat oqldeaioloylesl ' studies on vinyl chloride reported '& tJ^W^rstarf..:'' ^ 1. Viola,, in an atteapt to produce aqypastoolysis in animals, exposed tats f hours per ddqrs per week to fd.MO ppm (3%) vinyl ebloride vepor. v <ge&, March; 1979). Xu his first report on the results of 1) uonths exposure* he described eetaplastis changes in the heeds which he con sidered similar to the human disease aeroostoolysib. Be smde no mention of having observed sancer in these animals vttil the Tenth International Cancer Congress in Nay, 1970. Ze the abstracts of this meeting, (Viola* 1970)* and sub sequently in May* 1971* Viola* Bigottl and Caputo (1971) reported tumors of the skin, lunys and bones occurring first after 10 months of exposure. The authors suaaarized this --merit as followss "Bats (Ar/IBE Mister strain) exposed for 12 months to vapors of vinyl chloride developed tumors of the skin* lungs* and bones. _ The cutaneous tumors* which always appeared in the area in which submaxillary and parotid glands are located* --have been histologically recognised as epldszaeid carcinomas, papillosum* and mucoepidermoid carcinomas. The morphological characteristics of lung tumors, which occurred in a lower percentage, were mainly of the adenocarcinoma type, with the T *% 7 *< J ire:' . "JECtfVECr - .:5 15SG >, X* B., and F. Flvy. tadcoloyy and Imi industrial solvents. 1939. la translated bv hi lenry r. tayth, Jr. 1941 Vm Oettingen, V. F., H.D. Aa halegaaatad aliphatic, olefinic, cyclic, arenatie, and aliphatic-aromatic hydrocarbons including the haloganated iasaeticidaa, tboir -toxicity and potential dancers. Public Health Service Publication Mo. 414, 0. S. Department of Health, Education, Halfare, Washington, P. C. 1955. Mastronatteo, S., I.P., A. M. Pisber, E. Christie, and B. Oansiger. Acute inhalation toxicity of vinyl Chloride to laboratory aniauls. toerican Industrial Hygiene. Association Journal, volune 21, MO. 5, October, 1*40. XOrkelean, X. B., P. Open, and T. X. Move. The toxicity of vinyl chloride as determined by repeated exposure of.*. .. laboratory animals. Aaerieni Industrial Bygiene AisocLation Journal, Volune 22, Ho. 5, ?p. 354-341.' 1941. Gabor, S., M. Lecca-Xadu, asd Z. Manta.' Certain Mechanical indexes of the blood in vox cars exposed to toxic subs tances i (benzene, chlorobenzene, v.iyl. chloride). Prcu..TokJ ikol. 1 Xlinika Prof. Zabolevanii Xhin. Etiol. Sb. 221-223.. 1942. Irish, D. D. Vinyl chloride, CH--CKC1 (Monochloroethane). "Industrial Hygiene. and Toxicology, Volume -2,- pp. 1303-1395. P. A. Patty, Editor. * 1942. e Lester, D., A. A. G_r_e__e_n_b__e_r_g_,__a__n_d__W__.__X___________Effects ..of sing[l'a-----a--n-d----r-e---p--e--a--t-e--d-----e--x--p-o--s--u--r-e--s--aofv-bunans end rata to vf%linlfy4ll eelhlio|aridtas'.iwAw7ni5etur,ijccnaMinrno-JoIA-tnTtiKtdMmiuioiessutrMiua4lHn.rygiene Association V' re l,, M. Mads, B. Pxeda, B. ttndaaz) U Xvaoof, ' **? C. Valaczhay. ^Xnst. Byg. Clnflj.j^Mpi -v .. Bucharest 13(5) , 409-419. If44. - ~ ............. - . ,v ' Hertfif, 0, Sfc' T. CMerocarbons and ehl vinyl ehleflde. Kirk-Othner Bacycl. - 2nd at. 5, 173-179. 1944. V - .** . . B. the physiological properties of propellants. Aerosol Age 9(4), 44, 47-4S, SB, 99-91, 1944. GOQVZ8ZZ J BFG22714 r?ECltfEE3 JAN 26 1990 K. Vinyl chloride. Bahai <*- " * - - ~ d^goroacs,'!. and M. fobs.' (dayi'telold|kjf indsstriaf* tagieplOgic aspects.-; Mv> eyk. !7|l}4fW' IMf. $* la ten engagedrin tte poIyneriratiCn of -Belt. Mid. JtersAl. SSC7* py. 71|-)U. <a occurring atlorlda. \ 19(7. Mllsoo/*, M,, . _ J. 1. Creech. Occupational Acroostsolysffc, Journal of tte teorlean Medical Association, Volisae 201. _|,_pp. 57^591.. 19(7. Tuia, A. I.* and X. I. Alokbova. Pathogenic effect of --------ohronic exposure to rinyl- chloride -on-rabbita. Farnakol TOksikol, 31(3)x3(9--272. 19(9. Vhzin, A. ., and S. 1. Plofcheva. Pathogenesis of a disease, developing luring chronic action of vinyl chloride on tho organisa. Faraakol ToJcsikol 31 (3) x 30-372. 19S. Vasin, A. I., and I. Z. Plokhova. Creation of an experimntal aodol of "toxJ.e sngioneurosis* developing from the chronic action of vinyl chloride vapors on an organisa. 6X0 TX Prof Zabol 12(7)x47-49. 19(9. Aatonyuxhoako, V. A. Occupational poisoning by vinyl chloride. 020 TX Prof Zabol 12(3)x39-52. 1949. Baretta, S. O., X. D. Stewart, and J. X. tetchier. -------Monitoring Exposures to vinyl chloride vaporx breath analysis and continuous air sampling* teorlean Industrial Bygiono Association Journal, Volute 30, pp. 337-544. 1909. % J. i*>rv- * Vasia* A.- M., A. I. Plokhova. Changes in tha cardiac activity of rats chronically exposed to vinyl chloride rarnakol Tsksikol, 32 (2)i230-22l. lftftft. ehottak, Wolfgang. Toxicology of vinyl chloride. -----21(11)* pp. 7*1-71*. 1969. i* I. A.* and a. p. Granik. taog tem side effects of seats oceupatienal poisoning by certain hydrocarbons and their derivatives. CIS TA Prof Sabol 14 (3)>50-51. ' If7ft* r1 Basalaev* A. V. Experience with the ase of largo-frame photofloorography in exaalning skeletal hones of persons occupationally dealing with ansaturated hydrocarbons of the ethylene series (olefins) and their chlorine deriva tives (vinyl chloride, trichloroethylene). GIG TK Prof Sabol 14(11)t34-37. 1970* Kudryavtseva* 0. P. Characteristics of electrocardio graphic changes in patients with vinyl chloride poisoning. GIG TA Prof Zabol 14'S)>54-56. 157D. Viola, P. L. Patholoqy of vinyl chloride. Madieina del Aavoro, Volume SI* so. 3. March* 1970. translated from the Italian. 1970. Viola* P. X>. Canceroganic effect of vinyl chloride. Presented at the Tenth Zat. Cancer Cong.* Mooston, Texas. Begins Siena Znst. for Cancer Besearch* May 22-29. 1970. Pimsaa* s. 9.* W._A. Cook* W. M. Mhitehoose* H. -Magnuson, end T. Diteheck. Occupational Aeroosteolysist I. An Spidemiologieal Study. Archives of Environmental Health* --Vnloaa 22* pp. 61-73* January. 1971. Cock* V. A. * P. M. Clever, B. D. Dinaan* and S. J. Magnnaon. deeupatianal Aeroosteolysist ZZ. An industrial hygiene Study. Archives of Environmental Health, Volume 22, pp. 74-92. January. 1971. cal study. Archives of ^ /|pgp*LftVSly J*nuary^ l971. * A B* W# Bear* t 111 24**2^ * e^ -. : ** * - . - r_>c, . wiiatti. and A.- - S^KUi of ret kin* lungs* tmu&ut Besearch* Volume 31, Upt j .v.a^f-*4- ' . *f. t >. ->%- 4- *- - tm. . . :W '*T:- r - * ' O'" . TTOfrZSZZ y * BFG22716 Vinyl chloride. Boca--ntatlon of the IhraihoU Uait Velum American Conference of Governmental Industrial hygienists,Third Edition* 1971. Kr--r, C. 8.* and J. S. Hutehler. She correlation of clinical and environmental measurements for workers exposed to vinyl chloride. Mexican Industrial hygiene Association Journal* Volune 33(1)>19-30. 1971. Meyerscn* A. I. and 6. C. Haler. Cutaneous lesions in aeroosteolysis. Arch Dermatol 10( (2)*224-227. 1972. Jfihe* S. * and C. E. Lange. Long-term exposure to vinyl chloride. Dt. and. Wschr. 97x1972. Basalaev* A. V.* A. H. Vasin and A. C* Kochetkov. Pathogenesis of changes developing due to long-tera exposure to the effect of vinyl chloride. GIG TR Prof Xabol 16 (2):24-27. 1972. Markowits* 8. S., C. J. McDonald* W. Pethiere and M. S. Xarsner. Occupational aeroosteolysis. Arch Doxaatol 106(2):219-223. 1972. Jfihe* 8.* C. E. Lange* G. Stein* and 6. Veltstan. Uber die sogenannte Vinylchlorid-Xrankheit. Dtsch. ned. Wschr. 98, pp. 2034-2037. (German). 1973. Jfihe* 8.* C. E. Lange* G. Stein, and 6. Veltman. On the so-called vinyl chloride disease. Deutsche Medisinische Wochenschrift, 98(43), pp. 2034-2337. English translation. 1973 Levina* N. M. * V. 8. Filatova* B. G. Belaya, 8. A. Ashirova, T. P. Tikhomirov, A. L. Levin, R. 8. Hostinskaya, and B. |. JCusnetskii. hygienic certification of the building pnjeetl development, and reconstruction of plants pro ducing organochlorine products. Gif* Shnit (4)i88-87. - 1973* . * : .V ^*. - . v` ' ", Filatova* V. 8. , V. I. Vinogradova* and k 8. Bashkirova, hygienic evaluation of working conditions n some chemical plants operating in the open air. Gig. Tr. Prof label * -*CM8-ll. 4973. '*** ' * .*4 *-.* 22824012 BFG22717 T