Document 9gEQeygw3o7M1QxM5BEz8KNq

R&S 040589 ^/i' <.f. aa i, ^ C^y' /_ ) / Cm') " -C^ ^r-> /'-^vP*- '?<< s'- ~'\- /, A AA-r^.. Ps-^S-A pPcY^c, .'f&P J<y_ lA'A'ic. CC./L-rSl/e.' / / Tf* yv-y. *y-<- -'-->- \.CCsi-S^ r C/- S-i.'-ySi. r(y>- r\*0v .v?tc pS/e/O. y j7'I < - / -</ -;/*" cPj y . my- '-/ '' /' y^yfl^ Y/ yC/^p* t <s(s<***a' /PrY KB 2 5 1981 VCM TECH CTR Y^ At A. . Z)C~ - *c C-: VINYL CHLORIDE Ciiioroeffione CH: - CHCi TLV, 5 ppm ( -- 10 mj/iii1) -- \ppt_-ndi\ Ala nacogniaed Carcinogen r. CCvji .'<_'>>, hi^hi) ',ic.::un.-.bie ,is .-, ,;n a:. ;, j, ,/iiur, W"V( t h iui IOC' hUs <- nlUil'l UId f height u` tlj do, /*' boils at -13.9 C and freezes at -159.7 C. Vinyl chloride is usually handled as a li.iuid under pressure, and co.'.tainirg a pchmerdation inhibitor (phenol). It is slightly soluble in ..=- ter. but d'Ssohed b> akunol and ether fhf- rh:C< use oi \ m\! chloride 11 J( <1 'an c m; ;hc manufaciurc of no!\ vinyl chloride icjmi I: o .`on . in ployed in organic svniheses. Since vinvl chloiide is a gas ai room ir'innnraKjrc flnri p.C'Mjr-^, '.he eonvhon 'oete Oi ii'VK a-' j I- i/i i.'.' 'ion. As wiih many liquified gases, con'an oi !ni- 4,m o: R&S 040590 eyes with escaping compressed vinyl chloride can produce freezing frostbite.!1) Vinyl chloride has long been considered to be very low in toxicity by acute inhalation. Lehmann and Flurytzi sum marized the literature and reported work by Schauman v ho considered vinyl chloride to be a candidate surgical anesthetic. Schauman reported little pathological change even after repeated exposure to anesthetic concentrations. Further work on the anesthetic potential of vinyl chloride indicated that vinyl chloride was unsafe for use as a surgi cal anesthetic in dogs and that because of its flammability, poor efficacy and its ability to cause cardiac irregularities at anesthetic concentrations vinyl chloride was not suitable for use as an anesthetic in humans. Despite the early reports ascribing low toxicity to vinyl chloride, injury during the production of polyvinyl chloride (PVC) resins was reported as early as 1949. Significantly this report came from Europe where production of PVC in Eu rope preceded U.S. production by several years and today the quantity produced in Europe still exceeds U.S. produc tion by about two fold. In 1949, Tribuhk et aM reported numerous effects in PVC workers in what, by today's stan dards, must be considered as primitive production facil ities. These authors found a "considerable number of cases of hepatitis among workers" but were more concerned with other hepatotoxic chemicals such as chlorinated di phenyl and chlorinated naphthylene (Holowax [sic]) than they were with vinyl chloride. As a result of two deaths in Canada, the acute inhalation toxicity of vinyl chloride was studied by Mastromatteo et aAJ) who reported that exposure of mice, rats and guinea pigs to 10, 20 and 30 volume percent vinyl chloride caused the following mortality: NUMBER OF DEATHS IN DIFFERENT CROUPS OF FIVE MICE, RATS AND GUINEA PIGS EXPOSED FOR THIRTY MINUTES TO VARYtNC CONCENTRATIONS OF VINYL CHLORIDE IN AIR Vinyl Chloride concentration (percent by volume in air) Laboratory- animal Mice Rats Guinea pigs TOTAL 10 0/5 0/5 0/5 0/15 20 1/5 0/5 0/5 1/15 30 5/5 5/5 1/5* 11/15 40 -- -- 2/5* 2/5 "A delayed death occurred within 24 hours following exposure. Some pulmonary hyperemia and engorgement was ob served by these investigators, but liver and kidney injury were remarkably low. Deaths weie due to narcosis. The first report of studies to determine the effect of long-term repealed exposure (6 months) wete Summarized be T ?,rkehon, Oven and Roue(1* as follows c .>'-,Et.'/U' of iahmaiuo aremais .v several . or )' :> " \ r; v / . h/:'.no e mao 'to ci induct ed io determ,ne me dcomc tuxici'o of this matetiai towards animats m outer to assess the hazard to hu mans \'inyl chloride was found to have a slight ca- /.ii/'v me' .i'f.j \,'s..-c*y tj*. i.iVj e<O'.aie and female rats siiuwet: mu 'Opatho- logical changes aftei repeated daily 7-hour exposures -tztt at SIX) ppm for 4.5 months. Repeated 7-hour exposured at 200 ppm for six months resulted in micropathological changes in the livers of rabbits and statisti cally significant increases 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 species were not affected. All species studied tolerated re peated daily 7-hour exposures at 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 expo sures caused a slight increase in liver weight. The standard for evaluating regular daily 7- or 8-hour exposures may be defined as the concentration be low which practically all Analytical results must fall. The value of 100 ppm is suggested as this standard for vinyl chloride, with a time-weighted average for all exposures not to exceed 50 ppm." Lester, Greenberg and Adamsi5) took exception to the conclusion of Torkelson et al (1961) that 50 ppm should be a maximum time-weighted average exposure for workers. On the basis of 3 months exposure of rats to 2 volume percent and 19 days to 5 volume percent, they concluded that 500 ppm was acceptable as a TLV despite minor changes which they observed in rat livers and which they considered "were within the normal range and were not pathologic in nature." Since 1949 numerous articles describing conditions and problems in PVC production plants have appeared particu larly in the Eastern European literature. Filatova and Cronsberg.w Gabor et alw Suciu et al,w Gabor et al,w Grigorescu and Toba,<10> Antonyuzhenko,!11) and Kudryavtseva!13) have all described the effects of apparent gross chronic exposure. These papers and abstracts are difficult to inter pret since there are generally inadequate descriptions of the exposure conditions and analysis of the workroom air, so no dose-response relationship can be determined. The injuries and effects described by the authors are not con sistent with the levels of exposures claimed by (he authors nor are the levels of exposure consistent with past or even present-day chemical technology. Furthermore, mixtures of chemicals are involved making it possible to ascribe the effect to any one of them. For example, Suciu et a/*3) (through translation) de scribed nervous disorders including euphoria with whis tling and laughing, incoordination and dizziness similar to alcohol intoxication. However, Suciu et al ascribes these results lo exposure of the order of 5.5 mg/m3 (2 ppm v/v) which is not consistent with other publications which indi cate these effects will be apparent only if concentrations greatly exceed 10,000 to 20,000 ppm v/v. Therefore, the fol low ing conclusions by the authors can he construed as being the result of massive and appamntlv repeated expo- -ures: 1 t "i/7r i i end the vinvl monomers possess a narcotic action and produce, d-:pei,ding upon <. on; cntrjiion, in addition lo characteristic neuro logic manifestation, a state of euphoria (12%), fol- ' . .' :. J -.'.i.v of it,delation <imiia' to that of ah-ofml intoxication. In certain cases naiccsis can appear. After leaving the working environment, a stale of somnolence (45%) persists, with hypersomnia. Vi nyl chloride acts on the skin and produces a sen sation of formication and of heal. 2. After repeated exposure, a neurologic asthenia sets in which somnolence predominates. 3. After a variable period of time, dyspeptic distur bances are added to the neurologic manifestations; these are at first not characteristic; they are in the form of epigastric pains (16%), swelling, discomfort, feeling of heaviness in the right hypochrondium (7%) or the left (5%) with anorexia, particularly for fats. In 30.2% of the cases, congestive hepatomegaly ap pears, which may mimic toxic hepatitis without jaundice; some cases may become chronic. In 6% of the cases, the hepatomegaly is accompanied by splenomegaly. The proteinogram and the aldolas es are the most sensitive tests and show changes sim ilar to those of acute hepatitis: increase in a-globulins and of the )3- and y-globulins; and thymol test, Creenstedt's reaction and the zinc sulfate test are positive only in few of the cases. 4. After 3 years of exposure in 9% of the cases a syn drome typical of ulcer without radiologic changes becomes manifest. 5. In 6% of the cases the Raynaud syndrome has ap peared, particularly among the young men. Plethys mography shows in half of the cases an inhibition of the vasomotor centers. 6. In addition, allergic dermatitis in 4.4% of the cases, and scleroderma in 3.6%, has been observed. 7. The clinical and laboratory findings are of great im portance in occupational pathology because in num erous cases diseases appear in man that cannot be reproduced in the animal (Raynaud's syndrome and scleroderma). The sudden and frequent appearance of these mani festations in the PVC division of several plants, and in certain divisions in normal individuals who are still relatively young, and their disappearance in the ma jority of (he cases after the institution of protective measures and change of work, have shown us deci sively that vinyl chloride and the vinyl monomers have played a part in the production of these mani festations. (End of author's summary). In 1967, reports appeared in the literature describing a condition known a' acroosieolysis in workmen engaged in polymerization of vinyl chloride to poiyvmyl chloride. Har ris and Adams'13) reported on two cases m Europe. Wilson ei a/-'14' reported on 3? cases in the B. F. Goodrich Compa ny, juhe et a/nsi described a syndrome consisting of (ar ranged in decreasing order of occurrence) thiombopema, rrl"nom,'ealvl liver damage, obstruction of ventilation, circ'i:i'10r\ !rucj io". and skin and v alteration o ii of ; i i:< piubi.ru"i, `he k *_*' si1 v G! Vi :n 'c. p <; ;F6-!c(.r,"(i bv the v.anufai to r.ng Divines:.S A^O- ('nblOu :io *n u a: (1 a* roosu-olysis ir: >pun_-.u. mh Ann,-n- can comptir.iif-S 1 hf? ; osults of a !.vge --c ale epuiv-mu a; -rods o: w or kers i hoia currently emplos rd in v invl i. Mor ide ; .' ! u, :. , ( P)'. i.-' ' - '-nor;"d ; r :lt r 'Mica! ions by this groan Drnm.in (V a!,1'M ,'ok and llrv.ison et a/31BI Dinman et aA16' summarized the study as follows: "An epidemiological study was performed cov ering 5,011 employees with 21,510 man-years ex perience in various phases of vinyl chloride (VC) and polyvinyl chloride (PVC) manufacturing in 32 plants throughout the United States and Can ada. The total number of definitive cases of acroosteolysis (AOL) was 25; 16 other individuals were under suspicion. This condition is clearly associated with the hand cleaning of polymerizers. Workers engaged in other phases of VC or PVC manufacturing do not appear to be at risk of developing AOL. The importance of Raynaud's phenomenon as a concomitant of AOL us emphasized. Several statistical ap proaches for rapid medical survey are suggested. Acroosieolysis appears to be a systemic rather than local disease. Presently, neither the eti ological agent nor its portal of entry is known." Cook et ainn describes the polyvinyl chloride produc tion process in considerable detail. They concluded that although no etiological agent could be identified, "There appeared to be a correlation between the extent of degas sing prior to entry into the reactor" and the incidence of acroosteolysis. Mutchler and Kramed1') presented a paper at the 1968 Cordon Research Conference which was subsequently published (1972), which reported on The Correlation of Clinical and Environmental Measurements for Workers Ex posed to Vinyl Chloride. The authors drew the following conclusion: "Our findings suggest that repeated exposure to vi nyl chloride at TWA levels of 300 ppm or above for working lifetime together with a very low level c yy vinylidene chloride may result in slight changes certain physiologic and clinical laboratory pararr, ters. The possibility of some impairment in Ih function tests must be considered, even though to overt clinical disease was evident in any of the ir -* viduals studied. We shall continue our study, suggest that similar studies to help clarify the eff of this material be performed for other worker popu lations exposed to vinyl chloride alone." P. L. Viola, in an attempt to produce acroosteolysis in animals, exposed rats 4 hours per day, S days per week to 30,000 ppm (3%) vinyl chloride vapor. In his first report on the results of 12 months exposure, he described metaplas tic changes in the bones which he considered similar to the human disease acroosteolysis. He made no mention of having observed cancer in these animals until the Tenth International Cancer Congress in May 1970. In the abstracts of this meeting, and subsequently in May 1971, Viola, Bigotti and Caputo,:l> reported tumors of the skin, lungs and bones incurring first after 10 months of exposure. The auiVjr; -awmarired this work as follows, 1 .r.:P -\t t'r.r W'star strain) expo-ed for 77 r,-earths to . of > u'.vl chloride developed tumors of the Li muf hones, The cu.'j.vu:.1' .-.hii.h .b appeared in the area in which <-ub.naultar) and parotid glands are located, ha\c been hetO'Ogi- . :'!\ re: opnized as epidermoid carcinomas, papillo mas, and muuuL-piduiinoid : arLii'.r:::.!;. 7/.-. .m, pno- logicai characteristics of lung tumors, which 429 R&S 040592 occurred in a lower percentage, were mainly of the adenocarcinoma type, with the exception of a single epidermoid tumor originating from the epithelial covering cells. In a minor number of rats, a large pro liferation of cartilaginous tissue diagnosed as osteo chondroma developed in the metacarpal and meta tarsal regions of the four limbs." The report by Viola et aA21) is apparently the earliest publication in which carcinogenic activity has been as cribed to vinyl chloride in man or animals. Although there were obvious deficiencies in Viola's study, such as his very impure sample, the presence of food and bedding in the exposure chamber, the excessive exposure concentration as well as in the statistical evaluation and interpretation of the tesions, the report was of serious concern and resulted in additional animal and epidemiological studies which are currently underway in Italy by Maltoni/22) Maltoni and Lefemine<J^) and in the U.S., Keplinger ef a//35) On January 22-23, 1974, the B. F. Goodrich Company notified its employees, NIOSH, the Kentucky State Depart ment of Labor, and the public, that three workers had died of angiosarcomas of the liver. The case reports of the first subject has been published by Creech and Johnson.ww The subject, a 36 year old male, was hospitalized January 5,1970 and subsequently succumbed September 27,1971. He had worked in PVC production from November 1955 until his illness. The history, clinical course and pathologic findings are consistent with the others who died of angiosarcoma. The work of Maltoni and Lefeminet33-2-*) has been report ed publicly at the OSHA hearing, Washington, D.C., Febru ary 15, 1974, and included in the 1974 publication of the Second International Symposium on Cancer Detection and Prevention, Bologna, Italy, April 9-12,1973. In these studies groups of rats as well as mice and hamsters have been ex posed at concentrations of 10,000 to 50 ppm vinyl chloride vapor. Maltoni and Lefemine (1974) reported carcinomas of the Zymbal glands, nephroblastoma and angiosarcomas of the livers of rats at concentrations of 250 ppm to 10,000 ppm but not at 50 ppm. Subsequent unpublished informa tion (August 31, 1974) reported, "1 liver angiosarcoma, 7 extrahepatic angiosarcoma and 7 nephroblastoma, in three animals of the first experiment, exposed at 50 ppm of VC for 7 year, and surviving 135 weeks from (he beginning of he treatment." The authors conclude that, "a dose-response relationship clearly emerges, as far as angiosarcomas and nephroblastomas are con cerned, in the lower dose ranges: from 500 ppm to 50 ppm for angiosarcomas, and from 250 ppm to 50 ppm for nephroblastomas. A comparison of the results available at the present moment in rats exposed for 12 months and A months (BT1 and BT3 experiments) shows that the neoplastic response, as far as angios arcomas and nephroblastomas are concerned, is af fected by the length of exposure to VC." in thei' experiment BT3 Maltoni and Lctem'ne imported o'' i:~,'n; ; xr,>;ixr-d a; 10.i/V ,-nri 'yw - ->- kc.; .Lv,f a d/,1-1' in c > bi *c.' . ;> / 'm un companies, have confirmed me finding- ui ''..s.ic-r-.. nnd lefemine. In this study, groups of 100 rats, mii.e -md hum- s;<'< rr r. -'I s*e bi-ine exposed seven hours p'-r dax1. live nays per week to either 2,:>u0, ZUG to ?0u ppm unvi chloride monomer. After sexon months o; exposure j.n- 430 giosarcoma and lung adeaomas have been observed m mice at all exposure levels. Although the data are prelimi nary in nature and require confirmation, angiosarcomas were apparently also observed in rats at 2,500 and 200 ppm and in a single hamster at 2,500 ppm. This study is still in progress and will not be completed until 1976 or 1977. Epidemiological studies on U.S. workers have been con ducted by Tabershaw-Cooper Associates for the Manufac turing Chemists Association.t37> The summary of this study is as follows: This historical prospective mortality study of 8384 men who had at least one year of occupational exposure to vinyl chloride before December 31, 1972, demonstrated that cancers of the digestive system (primarily angiosarcoma), respiratory sys tem, brain, and'cancers of unknown site, as well as lymphomas, occurred more often than expect ed in those members of the study population with the greatest estimated exposure. The mortality from other cancers was lower than that of the general male population, with the exception of cancers of the buccal cavity and pharynx. The ex planation for the latter finding is not apparent. The other major findings of the study are: (1) The over all mortality of the study population was approximately 75% of xvhat would be expected in a comparable popu lation of U.S. males; (2) No cause of death showed a statistically significant excess over what would be ex pected in a comparable U.S. male population; and (3) No deaths identified as angiosarcoma of the liver were found other than those previously identified. This is the first epidemiological study which suggests that in humans vinyl chloride may also be associated with cancer of multiple sites. It is difficult to derive a reasonable TLV from the data presented in the literature summarized above. There is in direct evidence that intermittent exposures to vinyl chlo ride of the order of thousands of ppm, in this country as well as Russia, have not been infrequent in PVC plants. No data on the past (or even present) concentrations of vinyl chloride in plants where angiosarcoma cases have oc curred, or not occurred, appear to be ax'ailable. One re port^) indicates that 21 of 26 of the early cases of angiosar coma occurred in former reactor cleaners. Cleaning of reactors was apparently responsible for most of the acroosteolysis cases investigated by Cook and associates/13) and has resulted in death from acute poisoning by vinyl chlo ride. W It is the sense of the Committee that, if the average exposure to vinyl chloride does not exceed 5 ppm, there wil be no increase in the incidence of cancer, specifically of angiosarcoma of the lixer. It is probable that the cancers reported and attributed to vinyl chloride among PVC work ers resulted from exposures many times this level. NIOSH recommend-'d a limit of 1 ppm as a TWA, uith a ceiling of 5 ppm The 1 ppm xaluc war appaienUy hai-ed on :hc "norv'o'.'x belief that thb was !he lowest concent.-a:ion that could be readily measured. Cehring and cc-workers/10' using a probit model, and haxed on studies with rats, found the predicted incidence ui injpowc etigiu'dLu.'r.di' iiuin o fix tufr , 5 (;<*)$ 35 y-at exposure at 7 ppm to be 1.5 times 108. Recent papers have included a report of 4 cases of respi ratory cancer among vinyl chloride workers, but no doseresponse relationship.^1) On the other hand. Fox and Collier,!33) in a study of 7000 men exposed to vinyl chloride in PVC manufacture be tween 1940 and 1974, found no evidence of cancers due to vinyl chloride at sites other than the liver. There are four liver cancers, two of them angiosarcomas. Deforme and Theriault^ described 10 cases of liver an giosarcoma among workers in vinyl chloride polymerizing plant in Quebec, which were accompanied by fibrosis of the liver. Details of 64 cases were presented by Sputas and Kaminski.^ Mutufugi, in Japan, noted that in contrast to western countries, in which 70 angiosarcomas cases (associated with vinyl chloride exposure) had been reported, no can cer, but many poisoning cases, have been reported in the USSR.OM Based on the above data, an Ala classification as a con firmed carcinogen is given vinyl chloride and a TLV of 5 ppm as a time-weighted average is suggested. If this value is not exceeded, there should be no increase in the inci dence of cancer, especially angiosarcoma of the liver. Limits adopted in other countries, subsequent to the surfacing of vinyl chloride exposure associated cancers, as are follows, according to a 1977 summary: Australia (1973) 25 ppm; Finland (1975), Holland (1973), Poland (1976),. Switzerland (1976) and USSR (1977) about 10 ppm; Italy (1975) 5 ppm; Japan (1975) and Sweden (1978) 1 ppm. References: 1. Torkelson, T.R. et al: Am. Ind. Hyg. Assoc. J. 22(5)-.354 (1961). 2- Lehman, K.B., Flury, F.: Toxicology & Hygiene of Industrial Solvents (1938). 3. Tribukh, et al: Arg. Saint. 70.38 (1949). 4. Mastromatteo, E. et al: Am. Ind. Hyg. Assoc. ). 21(5):394 (1961). 5. Lester, D. et al: Ibid. 24:265 (1963). 6. Filatova, V.A., Gronsberg, E.S.: Cigiena i. Sanit. 22(1):33, ab stract (1957). 7. Gabor, S. et al: Prom. Toksikol. i. Klinika Prof. Zaholevanii Khim. Etiol. Sb. 221, abstract (1%2). 8. Suciu, I. et al: Medicina Interna (Bucharest) XV(8):967 (1963) 9. Gabor, S. et al: Ingiena Bucharest 7J(5):409 (1964). 10. Grigorescu, I., Toba, G.: Rev. Chim. 17(8):499, abstract (1966). 11. Antonyuahenko, V.A.: Gig. Tr. Prof. Zabol. 12(3):50, abstract (1968). 12. Kudryavtseva, O.F.: Ibid. 14(8).54, abstract (1970). 13. Harris, D.K., Adams, W.G.F.: Brit. Med. J. 5567:712, abstract (1967). 14. Wilson, R.H. et ah JAMA 201(8):577 (1967). 15. Juhe, S. et al: Dtsch. Med. Wschr. 98:2034 (1973). 16. Dinman, B.D. ef al: Arch. Env. Health 22:61 (1971). 17. Cook, W.A. et al: Ibid., p. 74. 18. Dodson, V.N. et al: Ibid., p. 83. 19. Kramer, C.G., Mutchler, J.E.: Am. Ind. Hyg. Assoc. J. 33(1):19 (1971). 20. Viola, P.L.: Medicina del Lavoro 61(3) (March 1970). 21. Viola, P.L et al: Cancer Research 37:516 (1971). 22. Maltoni, C: Proc. 2nd Inti. Symp. on Cancer Detection & Pre vention, Bologna, 1973, Excerpta Medica, Amsterdam (1974). 23. Maltoni, C-, Lefemine, C.: Lincei-Rendiconte Della Classe di Science, Tesiche, Mathmatische 56:1 (1974). 24. Eidem: Carcinogenic Bioassays of Vinyl Chloride, unpub lished data (1974). 25. Keplinger, J.L. et al: Annals of NY Acad, of Sciences Working Croup (May 10,1974). 26. Creech, J.L., Johnson, M.N.: JOM 76(3):150 (1974). 27. Tabershatv, I.R., Gaffey, W.R.: Ibid., p. 508, 28. Patty, F.A. et al: U.S. Pub. Health Reports 45, 1963, abstract (1930). 29. Current Intelligence, J, Occup. Med. 76:809 (1974). 30. Gehring, P.T. et al: Tox. Appl. Pharm. 49.15 (1979). IHD ab stract 753/79. 31. Buffler, PA., et al: J. Occup. Med. 27:195 (1979). Ibid. 54/79. 32. Fox, A.J., Collier, P.F.: Brit. J. Ind. Med. 34:1 (1977). Ibid. 501/77. 33. Delorme, F., Theriault, G.t J. Occup. Med. 2(7.338 (1978). Ibid. 688/78. 34. Sputas, R., Kaminski, R.: Ibid., p. 427. Ibid. 828/78. 35. Matufugi, H.: ) Science Labor 54 585 (1978). Ibid 54/79. 36. Massachusetts Div. of Occup. Hygiene: Unpublished report. References: 1. Lucas, G.H.W.: }. pharm. 34:223 (1928). 2. Von Oettingen, W.F.: The HalogcnatedHydrocarbons, Toxici ty and Potential Dangers, US Public Health Service Publ. No. 414, p. 152, Washington, DC (1955). 3. /(ochrr.ann, M.: Muench filed. Wochschr. 7.S.1334 (192H) Cit ed in ref. 2, p. 153. 4. Olmstead, E.V.: Arch. tnd. Health 27:525 (1960). 5. Rowe, V.K., Spencer, H.C., McCollister, D.D., Hollingsworth, R.L., Adams, E.M.: Arch. Ind. Hyg. & Occup. Med. 6:158 (1952). 6. Rowe, V.K., Hollingsworth, R.L, McCollister, D.D.: Agric. & Food Chem. 2:1318 (1954). 7. McCollister, D.D., Hollingsworth, R.L., Oyer^ F,, Rowe, V.K.: Arch. Ind. Health 13:1 (1956). 8. NIOSH: Criteria for a Recommended Standard -- Occupa tional Exposure to Ethylene Dibromide, DHEW (NIOSH) Pub. No, 77-221 (1977). 9. Kochmann, M.: Muench. Med. Wochenschr. 75.1334 (1928) Cited in ref. 8. 10. Olson, W.A, et al: j. Natl. Cancer Inst. 57:1993 (1973). Ibid. 11. Powers, M.B. et al. Tox. Appl. Pharm. 33:171 (1975). Ibid. 12. Ward, J.M., Haberman, R.T.: Lab. Invest. 30.392 (1974). Ibid. 13. Idem: Bull. Soc. Pharmacol. Env. Path. 2:10 (1974). Ibid. 14. Ott, M.G., Scharnweber, H.C., Langner, R.R.: Unpublished re port submitted to NIOSH by the Dow Chemical Co. (1977). Ibid. 15. Stanford Research Institute: Report submitted to NIOSH un der contract No. DCD-99-74-31 (1976). Ibid. 16. Amir, D., Volcani, R.: Nature 206:99 (1965). Ibid. 17. Alumot, E. ef al: Poult. Sci. 47:1979 (1968). Ibid. 18. Short, R.D. Jr. et al: Report No. EPA-560/6-76-018, US Enviror mental Protection Agency, Office of Toxic Substances (1967 Ibid. 19. NIOSH: Toxic Substances List, H.E. Christensen ed., p. 4 (1973). R&S 040594 ETHYLENE DICHLORIDE 1,2-Dichloroethane CHjCICHjCI TLV, 10 ppm ( == 40 mg/m3) STEL, 15 ppm ( as 60 mg/m3) Ethylene dichloride is a colorless liquid with the odor typical of chlorinated hydrocarbons. It has a molecular weight of 98.96 and, at 20 C, a specific gravity of 1.2569 and a vapor pessure of 62 mm Hg. The boiling point is 83.5 C, freezing point is -35.5 C and dosed cup flash point is 55 F. It is soluble in about 120 parts water and miscible with alcohol, chloroform and ether. It has been used as an intermediate in the manufacture of vinyl chloride, a scavenger in leaded gasoline, a degreas er, fumigant, solvent, and in paint removers, welling and penetrating agents, ore flotation and soaps and scouring compounds. Animal studies have uniformly indicated liver and kid ney injury from ethylene dichloride, although to a lesser extent than from comparable exposures to carbon tetra chloride. Smvth ef af" reported an oral I Dsc, in rats to be 770 mg/kg Heppe! and associates,*21 on the 'oasis of animal studies, concluded that ethylene dichloride is one of the more tox ic of the common chlorinaled hydrocarbons They found increased mortality m 5 species of animats exposed 7 hr/d, 5 d/wk, at 200 ppm. Loss in weight, pulmonary' congestion and liver changes were noted. At 100 ppm rats bred sucteWmi-, a.scf aumpy. re-, c-iavd no abm: ma! findings t t: ! a t r v, i ^ * i: ; e s 1111' .t p, y > - , i ,: oi \ . *, .1.1 1i it-: d in 2.0 ppm. , '1 ! V, h I l V > i (3 i i I > at z, cj (.pm '4Hcifmann el al f r*un(i !t 10:h in.. >rt a!.;\ ins a.rir.u? s n-i it's .1 / 1.. ", 1 w 1 ) * ~ on n A: 'd' t 31s -fu 'v. or; ?. : ye. tu rate, out utii-v .ru.-- oes v.ere ut'.aflci ;r-u, Opacity of the cornea has been observed in d 'S and foxes following administration of ethylene dichloride, ac cording to von Oettingen,*5) A number of deaths from the accidental ingestion of ethylene dichloride have been reported. In addition, Browning16* noted three fatal cases from inhalation; liver and kidney injury were found in all, pulmonary edema in one. Several other episodes of occupational intoxication, with nausea and vomiting the predominating symptoms, have been reported.<s-7-8* Experience in one plant indicated that concentrations in the range of 25 to 50 ppm were safe for prolonged expo sure.191 Bardodej*10* however, considered it a most undesir able substance, comparable in toxicity to carbon tetrachlo ride. In its criteria document,*11* NIOSH cited French,*11) Ital ian,i13-14* German*13! and Russian*16* papers which indicated fatalities from inhalation of ethylene dichloride in concen trations insufficient to cause anesthesia. A Polish paper*17* reported symptoms such as nausea, vomiting and dizziness from exposures between 10 and 37 ppm in one of six work ers, and physical examinations revealed abnormalities, no tably blood changes, in 8 of 16 workers. The NIOSH recommendation for a workplace air stan dard at this time was 5 ppm as TWA, with a 15-minute ceiling of 15 ppm. This recommendation appears to have been based largely on a paper by Kozik*13'- in Russia. Work ers with exposures generally averaging below 16 ppm, but in a few instances between 30 and 50 ppm, experienced numerous adverse nervous system and liver effects. Another paper*1*/ reported no changes in blood or inter nal organs among 100 Russian workers exposed up to five s ai com eniraiio.u? i,>: e:'rn'i,.-ne dicnionti..- nut t rr*:- .'"z 25 pnm, hut , , da.00 and - >ir, . tre meed vt 1 v. ith a 2 ; 1 i.'iling.1'' C.-ncc ' g.. the h.. aim effeU- uc-irlvii'd <1 r:*:il- 1 i,; M. ind" I:r 1 -. !>.- Ionv-. ,n :t.< . o' 'no- r !-:; * j J o \ 'C (in u c(j < r \ vi , .. * - 0 : t > > '" ` \\ 111 * p' 1 f 11<";! 1 r\ f)<i f t l 11. l 1 I l `k ! ^ \ ' l' ! vi*.! .1*1 If- . t s i' < 1 < *1 187 R&S 040595 50 10 10 ppm has been adopted and a STEL of 15 ppm is recommendaied. Other recommendations from a 1977 listing: West Ger many, Sweden, Switzerland, 20 ppm; Czechoslovakia, East Germany, Romania, Yugoslavia, 12 ppm; Poland, U.S.S.R., 2.5 ppm; others, including Japan and the Council of Europe retained the 50 ppm value. In 1978 Sweden reduced its TWA to 5 ppm, and in 1979 West Germany added the de signation of potential carcinogen, but retained the 20 ppm MAK. References: 1. Smyth, H.F, Jr. er al: Am. Ind. Hyg. Assoc. J. 30.470 (1969). 2. Heppel, LA., Neal, P.A., Perrin, T.L, Porterfield, V.T.: ). Ind. Hyg. & Tox. 28:113 (1946). 3. Spencer, H.C., Rowe, V.K., Adams, E.M., McCollister, D.D., Irish, O.D.: Arch. Ind. Hyg. & Occup. Med. 4:482 (1951). 4. Hofmann, H.T., Birnstiel, H., Jobst, P,: Arch. Toxikol. 27:248 (1971). 5. von Oettingen, W.F.: The Halogenaied Hydrocarbons, Toxici ty and Potential Dangers, US Public Health Service, Pub. No. 414, p. 144, Washington, DC (1955). 6. Browning, E.: Toxicity & Metabolism of Organic Solvents, p.' 252, Elsevier Publishing Co.. Amsterdam (1965). 7. Wirtschafter, Z.T., Schwartz, E.D.: ). Ind. Hyg. & Tox. 27:126 (1939). 8. McNally, W.D., Fostvedt, G.: Ind. Med. 10.373 (1941). 9. Fassett, D.t Private communication to TLV Committee (1964). 10. Bardodej, 2.: in Documentation of MAC in Czechoslovakia, p. 63, Prague (1969). 11. NIOSH: Criteria (or a Recommended Standard -- Occupa tional Exposure Ethylene Dichloride, HEW Pub. No. (NIOSH) 76-139 (1976). 12. Olivier, H. el al: Soc. Med. teg. 34:261 (1954). Cited by NIOSH in ref. 10, 13. Guarino, A., Koia, N.: Folia Med. (Napoil) 41:676 (1958). Ibid. 14. Triosi, F.M., Cavallazzi, D.: Med. Lav. 52:612 (1961). Ibid. 15. Menschick, H.: Arch. Dewerbepath. Cewerbehyg. IS:241 (1957). Ibid. 16. Rosenbaum, N.D.: Cig. Sanit. 12(2):17 (1947). Ibid. 17. Brzozowski, J.: Med. Pracy 5:89 (1954). Ibid. 18. Kozik, I.: Cig. Tr. Prof. Zabol. 1:32 (1957). Ibid. 19. NIOSH: Special Hazard Review--Ethylene Dichloride (1978).