Document a1Ky57a1Vj2qKL9zjLMZp3XVY

Dr. Michael M. O'.Mara July 9, 1986 Page Two Keller and Heckman If you have an/ comments or questions or if I can be of any assistance, Dlease let me know. Cordially yours, Peter L. de la Cruz Enclosures cc: Charles E. O'Connell ((vw. /o encs.) Lewis R. Freeman, Jr. Roy T. Gottesnan, Ph.D> SPI-01323 r FOOD CHEMICAL NEWS Editor Louis Rothschild. Jr. Circulation Director Shirley Galant Managing Editor Raymond G3/ant Assistant Director Iris M Schwartz Assistant to the Editors Nataie Pargas Production Manager Dorothy Hill Assistant Editors Steven Goldschmidt, Assistant Managers Alice Wilkes. Madonna Leal Sonia Rothschild Associate Editors: Cathy Cooker, Dave Simon, Ron Grandpn VINYL ACETATE REPORTED A "WfeAK" CARINOGEN BY LIJINSKY Vinyl acetate has been found to be "a weak but significant carcinogen for Fischer rats." National Cancer Institute's Dr William L i j insky reported at an international conference on Occupational and Environm tal Significance of Industrial Carcinogens sponsored by the Collegium Ramazzini and held in Bologna, Italy (See following story). Citing "evidence" of weak care inogenicitv, Lijinsky noted that vinyl acetate is not mutagenic in short-term tests, expressing interest in structure-activity relations to help elucidate mechanism. In the rinking water study, the NQ scientist said 5 of 20 female rats at the higher dosages showeji carcinomas of the uterus, also noting 5 C-cell adenomas of the thyroid in the females. Celanese Corporation's Dr. Joh l J. Clary reported on rodent studies now underway, saying that the question is whether they will reproduce the findings by Lijinsky. He said a drinking water study starting with in utero exposure is now in its 15th month, with initial findings indicating no carcinogenic ty. A reproduction study at a high dose indicates a slight effect on fertility, he added, Clary said an inhalation study in rats and mice is now in its 21st month, with no signifiit ant results so far. Dr. Cesare Maltoni, Director o the Institute of Oncology in Bologna, said his laboratory also is testing vinyl acetate, re vealing that the study in its 27th month is nearing completion. Dr. Hannu Norppa, of the Insti1 :ut e of Occupational Health in Finland, said recent work indicates vinyl acetate is a str ong plastogen in bacterial systems, mammalian cell culture, and mammals in vivo. He said t is not a mutagen in the Ames test or in E. coli, but added that vinyl acetate metabo izes to acetaldehyde, which is not active in bacterial systems. However, Norppa saic that the acetaldehyde metabolite is a potent inducer of chromosomal aberrations. During the session of the conf rence in which results of carcinogenic tests- on a number of plastic packaging materials vere reported, National Toxicology Program's Dr. Ernest McConnell pointedly commentec that the papers reported at the meeting should be "open for peer review and debate." Maltoni Stresses Concept of AcceptaL le Ridt SPI-01324 Maltoni. whose Institute is cone erned primarily with hazards from occupational exposure to carcinogens, stressed at a t v 'o -day seminar for media representatives that widely-used compounds cannot be banned, b j t that decisions must be made on the level of risk that is acceptable. He commented hat plastic monomers represent "huge problems." Center for Policy Alternatives' Nicholas A. Ashford, who was a Consumer Product Safetv Commissioner during the Carter Administration, said that "nobody challenges the Food FOOD CHEMICAL NEWS (ISSN 001 S-6 J37) is published weekly for S525 per year and J335 lor additional subscriptions by Food Chemical News, I r c., 1101 Pennsylvania Ave.. S.E., Washington, DC. 20003. Secondclass postage paid at Washington, D C 2001 3. POSTMASTER: Send oddress changes to the above address. Fdt. O i ( K I , r :i . 1QFC COb an "! Drug Ad n, ir. i r a : ior," be clause to do it. t h. ha' 1 `h' CHf- Mir A! \; V. 1 r'- Del a no\ an:i-c'r Dr. James Huff, of the National Institute of Em ironmental Health Sciences said th; a po'ent carcinogen is found it is a "prodent put lie health course" not to u ait for a risk assessment but to immediately start reducing exposure. AFL-ClO's Sheldon W. Samuels hit "special purpose trade associations" whrch he said have been formed to frustra e attempts to regulate. As an example, he mentioned the American Industrial Hea th Council, which he alleged is attempting "to destroy" the system of regulating carcinogens. However. Dr. G. Battista \1 rim Bettolo. Director of the Italian National Academy of Sciences, referred to the "failure of the . . . Delanev clause" in the U S alleging that the statute blocks the setting of "realistic" limits. He said limits should be based on "ethical considerat ons" rather than on statutes. The reports at the Collegium conference of carcinogenicity of indirect additives appears to place more pressure on F DA and perhaps on Congress to do something about the Delaney clause. The agencx has already used a court-suggested de minimis policy in clearing acrylonitrile (See F 3 OD CHEMICAL NEWS. Sept. 17, 1984, Page 13), which was again reported carcinogenic it the Bologna meeting. Vinylidene Chloride Reported Carcinogenic SPI-01325 Dr. Giuliano Cotti, of the Inistitute of Oncology, reported that a vinylidene chloride mouse ingestion study showed "lim iied evidence" of carcinogenicity, and that an inhalation study in rats showed malignant tu nors. Listing routes of exposure to vinylidene chloride, Cotti noted that potato chips are packaged in polypropylene film coated with vinylidene chloride copolymer. In answer to a question, Ma toni said vinylidene chloride tested in the U, S. had beer, contaminated with vinyl chloride, but he said the material tested in Bologna was not contaminated. Calling for a better dose-re iponse investigation of acrylonitrile, with a determination of whether the rat is an appropriate model for man. Standard Oil's Dr. Dale E. Strother recommended research on interspecies effects, dose comparisons, inhalation dose-response in animals, and dose-response in humans. Maltoni revealed that an inh alation study on acrylonitrile is in progress, staling that gliomas and mammary tumo s have been found. 'Saying that the total number of malignancies showed a signi icant increase, the scientist noted increases in leukemias, which had not previously bee n reported for acrylonitrile, and for other tumors. Rather than be concerned about sit specificity, Maltoni urged attention to total malignancies. Strother said the National Cancer Institute is looking at a "large comprehensive stud\" of tumor sites. Dr. kVron Mehlman. of Mobil Oil. asked about differences between acrylonitrile studies by Dow Chemical and by the Institute of Oncology, and Maltoni said he used a different procedu e employing prenatal exposure. He urged research on the differing results of experiments as an aid in elucidating mechanism. Strother had reported that carcinogenicity of acrylonitrile in man is uncertain because of the disparity of tumor sites, noting thar rat tumors have been found in the zymbal gland and the forestomach, dui in humans in the lung. Noting that four epidemiological srudies indicated an increase in tumors in man. he added that the Environmental Protection Agency has raise I "serious questions" about three of the studies. <hM. ChUiuix f October 21. 19^' Pagr < F 00D CHF MIC AI V F S Voting hi5- long-term concern about occupational exposure to vinv I chloride , Di, Irving Selikoff, of Mt. Sinai School )f Medicine and President of Collegium Ramazzim. called it a "success story," noting that the monomer has been reduced to less than 1 f.p.n,. Maltoni said that recent rat est results on vinyl chloride showed an "exceptionally high onset" of tumors, and N'lTP's McConnell agreed that there were "a myriad of tun The Institute of Oncology's C r . Barbara Conti reported a "weak carcinogenic effect" f: styrene, but said more researj::h is needed before any conclusions are reached. Lijinks\ said he recently completed a styrene test, finding essentially the same results of rode" forestomach tumors with a dc se-response relationship. Conti's new long-term bioassa; involved ingestion, inhalation. and injection in Sprague-Da wley rats. Finland's Norppa reported that styrene is clearly carcinogenic in cultures of hu man lymphocv tes. Dr. Adriano Ciliberti, of the nstitute of Oncology, reported rat and mouse studies on propylene, saving that the le were no significant carcinogenic effects (See FOOD CHEMICAL NEWS. April 1. Page 2). METHYLENE CHLORIDE, TRJCHLO ROETHYLENE REPORTED CARQNOGENIC Both methylene chloride and i richloroethylene were reported to be carcinogenic at an international oncology confere nee held in Bologna, Italy, Oct. 6-10, sponsored by the Collegium Ramazzini (See pre< eding story). U. S. industry has voluntarily dropped use of trichloroethylene as a decaffemaring solve-.t for coffee, but a Food and D ug Administration proposal to ban its use is still pending (See FOOD CHEMICAL NEWS Oct. 3, 1977, Page 37). The status of methylene chlonce as a solvent has remained con|t roversial (See FOOD CHEMICAL NEWS, Jan. 7, Page 2; March 25. Page 38; April 8, Plage 36; and Aug. 26. Page 3). In a paper prepared for a tw q-day media seminar. Dr. Cesare Maltoni. Director of the Institute of Oncology, said "m ethylene chloride has been found to cause an increased incidence of subcutaneous sarc omas of the salivary region, and of benign mammary turin rats . . .. and a slight inc r|ease in benign and malignant hepatocellular tumors, and in neoplasms of Harderian g I ah ds in mice . . ." Dr. Ernest McConnell, of the National Toxicology Program, said there is "clear evident: of carcinogenicity" of methylene chloride. He' said lung and liver tumors were found in "both male and female" m c e, and that there was "some evidence of cancer in ma! rats and clear evidence of ca r|cinogenic ity in females." The rat tumors were of the mammary gland. NTP had coft ducted an inhalation studv. Hazleton Laboratories' Dr. Da id G. Serota described a drinking water study in rats ar mice conducted for the Natioi|i a! Coffee Association, sav ing that there were no treat mrelated effects except for son(ie liver effects. Serota said the statistically significant liver lesions in female rats shb uld be examined further. The scientist expressed the opinion" that the liver lesions were not "biologically meaningful" because the low incidence in the female control group was lower than in historical controls. He rep orted no increase in tumors in male rats, and no statistically significant effects in mice. SPI-01326 BORDEN CHEMICAL DIVISION OF BORDEN (NC received s MAY o 19^ DR. R. T. GGTTE3HL4/V May 7, 1985 The Vinyl Institute Division of The Society of The Plastics Industry, Incorporated 355 Lexington Avenue New York, New York 10017 Attention: Dr. Roy Gottesmar Meredith N. Scheck Dear People: In the event you have not seei it, I am enclosing a copy of a California ARB request for Vinyl Chloride health effects data. The bib liography is certainly worth placing into your files, and you could consider responding to them WL th any pertinent VI data. Sincerely, Nathan M. Blackman Environmental Affairs Manager NMB/kml Enclosure 511 LANCASTER STREET. LEOMIN ITER. MASS 01453 TELEPHONE (617) 537 171 1 SPI-01327 STArt Of caiifornia air resources 1107 O STREET P.O. BOX 7815 SACRAMENTO, CA 95812 board BORDEN CHEMICAL MAY 3 `1985 LEOMINSTER. April 4, lybo sgESr GEOfiGE DEUK-MEjIAN. Gc*^mo< Dear Sir or Madam: Subject: Request for Information Regarding Vinyl Chloride I am writing to request infor nation on the health effects of vinyl chloride as part of our toxic air contami nant program. This program is based on Health and Safety Code Sections 3965b et seq. which require the ARB to identify compounds as toxic air contami nants and once identified to develop and adopt control measures for such com oounds. After consultation with the staff of the Department of Health Services (DHS), we have selected vinyl chloride as a candidate toxic air contamina it to be evaluated in accordance with the provisions of Health and Safe :y Code Sections 39650, et seq. During our evaluation of vinyl chloride, we will consider all avaTlable health information regarding this coimpound. Additionally, we are soliciting information regarding possibl biological production of vinyl chloride. Before the ARB can formally i ilentify a compound as a toxic air contaminant. several steps must be taken. First, the ARB must request the Department of Health Services to evaluate tike health effects of candidate compounds. Second, the ARB staff must prepare a report which includes the health effects evaluation and then submit the report to a Scientific Review Panel for its review. The report submitted to the Panel will be made available to the public. Information submitted in response to this request will be considered in the ARB report to the Panel. Although any person may also submit information directly to the P< nel for its consideration, I urge you to submit all information at this time lor our consideration in the development of the report for the Panel. The Par el reviews the sufficiency of the information, methods, and data used by the DHS in its evaluation. Last, after review by the Scientific Review Panel, ijhe report with the written findings of the Panel will be considered by the Air Resources Board and will be the basis for any regulatory action by the Boarc officially to identify a compound as a toxic air contaminant. Prior to formally requesting the DHS to prepare a health effects evaluation of vinyl chloride, we are providi ng, pursuant to the provisions of SPI-01328 -2- April 4, 1985 Section 39660(e) of the Heal h and Safety Code, an opportunity to interested parties to submit informati on on the health effects of vinyl chloride which he or she believes would be imp drtant in DHS's evaluation of vinyl chloride as a candidate toxic air contamin < nt. In March 1985, we received alreference search on vinyl chloride health effects using the MEDLINE and TOXLINE Information Services. These information services include material available to the public in late 1984. The attached bibliography lists the references from this information search. We are requesting pertinent information on vinyl chloride health effects, including any material that may not be (available to the public, that is not included in the attached bib!iography. Pursuant to the provisions of the Public Records Act (Government Code Sections 6280 et seq.), the informatio you provide will be a public record and subject to puFTic disclosure, except :or trade secrets which are not emission data or other information which is ex?mpt from disclosure or the disclosure of which is prohibited by law. The i n ormation may also be released to the Environmental Protection Agency, which protects trade secrets and confidential information in accordance with federal law, and to other public agencies. which are also required to protect such information. To expedite the review process we ask that any information which you believe should be regarded as "trade s ecret" be clearly marked and separated from other information. You may identify portions of the information you submit as "trade secret" in accordance vith Health and Safety Code Section 39660(e). The claim of trade secrecy must be supported upon the request of the Air Resources Board. Other information claimed to be trade secret and information otherwise claimed to be exempt from disclosure may be identified as confidential in accordance with Section 91011, Title 17, California Administrative Code. Section J1011 requires that the claim of confidentiality be accompanied by specified su jporting information. I would appreciate receiving a ly relevant information you wish to submit by May 19, 1985. Your help in exiediting our review will be greatly appreciated. Please send the information to the attention of: Will am V. Loscutoff, Chief Toxi Pollutants Branch Re: Vinyl Chloride Cali ornia Air Resources Board P. 0 Box 2815 Sacrdmento, CA 95812 If you have any further questi cns regarding health effects information, please contact Mr. John Batchelder at (916) 323-1505. For any other questions, please contact Mr. Don Ames at (916) 322-8285. SPI-01329 -3- April 4, 1985 If you are not the person to wnom this request should he addressed, please forward it to the appropriate person in your organization. Also, please let us know whether you would 1i ce to continue to receive information inquiries for other candidate compoundjs and if not, if there is anyone in your organization to whom such re quests should be sent. Sincerely, Peter D. Venturini, Chief Stationary Source Division cc: Alex Kelter, DHS Lori Johnston, DFA Wayne Morgan, President CAPCOA Jan Bush, Executive Sec rjetary, CAPCOA David Howekamp, EPA Regi on IX Assemblywoman Sally Tanr er, Chairwoman, Committee on Toxic Materials Senator Ralph Dills, Chalirman. Committee on Governmental Organization Senator Art Torres, Chai rman, Committee on Toxics and Public Safety Hanageme|n t Emil Mrak, Chairman and Scientific Review Panel Members APCOs Attachment SPI-01330 V.nyl Chloride Ref*. (3/1/85) Anderson, D. 1982) The preiictibility of bioassays Prog Clin Biol Re*. 109: 143-48 Anderson, D. ind Richardson C. R. (1981) Issues relevant to the assessment of chemically induced chromosome damage in vivo and their relationship to chemical mutagenesis.. Mutat Res. 90 3 ) .24 1 - 72 . 3 Anderson, 0 , Richardson, C R., Purchase, I. F., Evans, H. J. and O'Riordan, N. L ' 1 R S1 : Chromosomal analysis in vinyl chloride exposed workers: comparison of the standard technique with the s is t er-chr omt i d eichange technique.. Mutat Res. 33< 1 > 1 37-44 . A Ander son, M. W , Hoe1, D . C and Kaplan, N. L. (t?80) A general scheme for the incorporation of pharaacokin etics in low-dose risk estimation for chemical carcinogenesis: ejcample--vin yl chloride. Toxicol Appl Pharmacol. 55(l):154-41. Anon '1780) The Carcinogenicity of Vinyl Chloride and Related Compounds (NTIS/PB8022904) Govt Reports Announ oements 5 Index (GRASI),. 11. Anonymous (1974) Editorial: /inyl chloride: the carcinogenic risk. (6018) .p13 4 - 5 . Br Med J I Antweiler, H. (1974) Studies on `.he metabolism of vinyl chloride. . Environ Health Rerspect . 1 7 p 2 1 7 - 9 . Apieldorf, R. and Infante, ? F (1781) Review of epidemiologic study results of vinyl ch1oride-reI ated compounds. . Environ Health Perspect. 41:221-4. 9. Bahlman, L. J . , Alexander, V , Infante, P. F., Wagoner, J. K., Lane, J. M. and Bingham, E. (1979) Vinyl hal des: carcinogenicity. Vinyl bromide, vinyl chloride, and vinylidene chloride.. Am Ind Hyg Assoc J. 40(4) :A3 0 , 32 , 34 . 10 Barbin, A., Bartsch, H., Leccnte, P. and Radman, M. (1981) Studies on the miscoding properties of 1 , N4-ethenoader ine and 3,N4-ethenocytosine , DNA reaction products of vinyl chloride metabolites, luring in vitro DNA synthesis.. Nucleic Acids Res. 9 ( 2 ) : 375 -8 7 . 11. BARTSCH, H. (1974) MUTACENICI TY TESTS IN CHEMICAL C ARC INOC ENESIS . IARCUNT AGENCY RES CANCERISCI PU8L. 13:229-240 12 BARTSCH, H., MALAVEILLE, C., BARBIN, A., PLANCHE, G. and MONTESANO, R. (1974) ALKYLATING AND MUTAGENIC METABOLITES OF HALOCENATED OLEFINS PRODUCED BY HUMAN AND ANIMAL TISSUES. PROC AM ASSOC CANCER RES. 17:17. 13. Bartsch, H.. Maliveille, C., Camus, A. M., Marte1-PIanche, G., Brun, G., Hastefeui1 Ie, A., Sabadie, N. , Barbin, A., Kuroki, T., Orivon, C., Piccoli, C. and Montesano, R. (1980) Validati on and comparative studies on 180 chemicals with S. typhimgrium strains and V7? Ciinese hamster cells in the presence of various metaboliting systems.. Mutat Ats 74(11:1-50. 14. Bartsch, H. and Montesano, R (1975) Mutagenic and carcinogenic effects of vinyl chloride Mutat Res 32 (2 i : p93- 114. 15. BARTSCH, H., TOMATIS, L. and ilALAVEULE, C. ( 1 9 8 2 ) QUALITATIVE AND QUANTITATIVE COMPARISONS BETWEEN MUTACENIC AND CARC 1 NOGENIC ACTIVITIES OF CHEMICALS. MUTAGEN:NEW H0RIZ CENET TOXICOL. 35-72. SPI-01331 ** 14. Sailer, A. and Rohrborn, G. mutagenic effects in mammals 13(11:1-7 1980) Vinyl chloride: an example for evaluating n vivo after exposure to inhalation.. Arch Toxicol. 17. Becker, C. E. and Coye, H. J. (1981) Recent advances in occupational cancer.. J Tosicol Clin Toiicol. Z Z ( 3 ) : 13 3-208. 18. Bingham, E. and Lane, J. M. ( 1 980 ) Vinyl halides -- carcinogenicity. . Vet Hum Toxicol 22(1)31-3. 19. Bolt, H. M. (1978) Pharmacokinetics of vinyl chloride.. Gen Pharmacol 9 (2):p91-5 20. Bolt, H. M., Pilser, J. G and Buchter, A.-(1981) Inhalation pharmacokinetics based on gas uptake studies. III. A pharmacokinetic assessment in man of "peak concentrations: of vinyl chlor ide.. Arch Toxicol. 98(41:213-28. 21. BOLT, H. M., FILSER, J. G., LAIB, R. J. and OTTENVAELDER, H. (1980) BINDING KINETICS OF VINYL CHLORIDE AND VINYL BROMIDE AT VERY LOV DOSES, IN: QUANTITATIVE ASPECTS OF RISK ASSESSMENT IN CHEMICAL CARCINOGENESIS. ARCH TOXICOL SUPPL. 3:129-142. 22. Bolt, H. M. , Laib, R. J., Xappus, H. and Buchter, A. (1977) Pharmacokinetics of vinyl chloride in the rat.. Toxicology 7 (2):pl79-8B. 23. Brand, K. G., Buoen, L. C. and Brand, I. ( 1 973 ) Foreign-body tumor igenes is by vinyl chloride vinyl acetate copolymer: no evidence for chemical cocarcinogenesis.. J Natl Cancer Inst 34 (3) :p12 5 9 -62. 24. SHAUN, F. . , 3CHOENE I CH , LEG (TOR, M. S., MCGREGOR, D. B. and MOHN, (1981) MUTAGENICITY OF SELECTED CHEMI IAL3 IN THE HOST-MEDIATED ASSAY, IN: COMPARATIVE CHEMICAL MUTACENESIS. ENVIRON iCI RES. 24:353-392. 23. Buchter, A., Filser, J. G., Pe er, H. and Bolt, H. M. (1980) Pharmacokinetics of vinyl chloride in the Rhesus minkey.. Toxicol Lett 6 (l):p33-6. 26. Bycikowska, 2. ( 1 9 82 ) CCarcino | en i c i ty ol vinyl chloride). Pol Tyg Lek (POLAND) 3 7 (3) : p 9 3 - 7. 27. California Air Resources Board (1977) Effects of airborne vinyl chloride. ARB Staff Report* 73-1-1. 127pp. 2! Chu, K. C. and Milman, H. A. ( 981) Review of experimental carcinogenesis by compounds related to vinyl cht ride Environ Health Perspect 41.211-20. 2? Clinmesen, J ( 1 9 9 2 ) I nternati<na I Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC working paper TG1/2/79. Mutagenicity and teratogenicity of vinyl chlorite monomer (VCM): epidemiological evidence.. Mutat Res. 98 ( 1 ) : 97-1 00 . 30. Collins, B (1982) Models for the pharmacokinetics of vinyl chloride (letter) Toxicol Appl Pharmacol (UNITED STATES) . 64 (2) :p362-3. 31. Coustou, F (1979) Carcinogenic risk of products used related industries.. IARC Sci Fubl (23) ;pl29-49. in the pharmaceutical and 31. Crump, K S., Cuess, H. A. and Deal, K. L. (1977) Confidence intervals and lest of hypotheses concerning dose response relations inferred from animal carcinogenicity data.. Biometri cs . 33 (3) : p 4 3 7 - 3 1 . SPI-01332 Dannahet, C. L., Tamburro, C H ind Yam, L. T (1981) Occupational carcinogenesisthe Louisville eipt:1tnci with vinyl ch 1 or i de-associatd hepatic angiosarcoma.. Am tied. 70 ( 2 ) .2 79-87. SEAN, B. J., ANDERSON, D. and SRAM, R. J. (1981) MUTACENICITY OF SELECTED CHEMICALS IN THE MAMMALIAN DOMINANT LETHAL ASSAY, IN COMPARATIVE CHEMICAL MUTAGENESIS. ENVIRt SCI RES 28.187-538. 53. Delorme, F. (1978) CAssociltion of angiosarcoma of the liver and hepatoma in vinyl ihloride worker). Ann A n a |t Pathol (Paris) 23 (2) , p l 0 5 - 1 8 4. de Meester, C., Duverger-vin Bog'aert, If., L amb o t t e - Va ndep a e r , M., Roberfroid, M., ?onee let, E. and Mereier, 1. (1930) Mutagenicity of vinyl chloride in the Ames test possible artifacts related to experimental conditions.. Mutat Res. 77(2)175-9. je Meester, C., Poncelet, direct or indirect mutagen 1 ., Roberlroid, Cproceedings I . K. and Mereier, M. (1979) Arch Int Physiol Biochim Vinyl chloride: 87 (3) :p420- Diet:, :. X., Ramsey, J. C and Vatanabe, P. C. (1983) Relevance of experimental studies t o. human risk. On iron Health Perspect. 5 2 . ' - l 8 . Diet:, f. X., R e i 11 , R. H . Vatanabe, P. C and Cehring, P. J. (1981) Translation of pharmacokinetic/biochemical data into risk assessment.. Adv Exp Med Biol. 134 Pt 3.139 9 - 4 2 4 . Doss , It. , Lange, . o ; ; a p o r ? h y r i n u: and Veit man, G. (1934) Vinyl chloride-induced hepatic with transition to chronic hepatic porphyria.. Xlin Vochenschr 1: Drew, R. T., Boorman, G. A , Haseman, J. K., McConnell, E. E., Busey, V. M. and Ms i: a, J. A. ( 1 9 3 3 ) The eff ect of age and exposure duration on cancer indu-c tion by a ic.town carcinogen in rats, mice, and hamsters.. Toxicol AppI Pharmacol. 48 ( 1 ) 1 2 0-30 81 Duverger, M., Lambotte, M., Malvoisin, E., de Meester, C , Poncelet, F and Mereier, M (1731) Metabolic activation and mutagenicity of 8 vinylic monomers (vinyl chloride, styrene, acrylonitrile, butadiene) Toxicol Eur Res. 3(3) : 131 -- 40 . 0 'i v i : g e c - V a n E o g a e r t , M . , L imbotte-Vandepaer, M., De Meester, C , Mereier, M. and "or. cel at, F (1932) Vinyl e iloride and acrylonitrile: activation mechanism and antigenicity. Toxicol Eur tes. <8(1) 35-7. 1, R . U I E. ?. N. and OTTENVAELDER, H (1 9 3 0 ) MUTAGENICITY OF ::: vitro and IN VIV: WITH YEAST A3 INDICATOR ORGANISM. NAUNYN- ARCH F H A A. 7AC L 311(3"J ? F L) 371. Elmore, J. D., Vong, J. L., Laumbach, A. D. and Streips, U. N. (1974) Vinyl chloiide mutagenicity via the metabolites ch 1 orooiirane and ch1oroaceta Idehyd monomer hydrate.. Siochin B ophys Acta 882 (3) :p805-19. Id Evans, D. M., Williams, V. and Rung, I. T. (1983) Angiosarcoma and hepatocellular circinoma in vinyl chloride workers.. HistopathoIogy. 7(3)377-88. i 7 E 4 o :i, J. H. ( 1 9 3 8 ) The imnu otoxicity of selected environmental chemicals, pesticide n J heavy metals.. Prog Clin Biol Res. U 1 3 3 5 - 4 3 . 13 Piuticant, J. D and Legator , M S (1981) Mutagenicity studies of vinyl chloride.. Environ Health Perspect. 81. 1 8 9- 73 . SPl-01333