Document rxa5zkz0JNXoxYOb0DQxYB9av

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 MAR 0 8 to jg 0) Oro (A to MAR | 1985 OFFICE OF , PESTICIDES AND TOXIC SUBSTANCES John A. Gray Attorney 2030 Willard H. Dow Center The Dow Chemical Company The Dow Center Midland, MI 48640 Dear Mr. Gray: This acknowledges your letter of October 5, 1984, providing information on vinyl chloride to the U.S. Environmental Protection Agency, Your submission has been screened as part of our current awareness program on existing chemicals and assigned the following FYI (For Your Information) Document Control Number: FYI-OTS-1084-0353 In any further communication with the Agency regarding this submission, please refer to the above Document Control Number and address your reply to: Document Control Officer (TS-793) ATTN: Mr. Terry O'Bryan Office of Toxic Substances U.S. Environmental protection Agency Washington, D.C. 20460 The Agency looks forward to continued cooperation with the Dow Chemical Company in its efforts to evaluate potential risks posed by chemicals to health and the environment. Sincerely, Frank D. Kover, Chi'ef Chemical Screening Branch/ECAD R&S 002460 THE DOW CHEMICAL COMPANY October 5, 1984 THE OOW CENTER MIDLAND. MICHIGAN 48640 Document Control Officer Management Support Division Office of Toxic Substances (WH-557) U.S. Environmental Protection Agency 401 M Street, S.W. Washington, D.C. 20460 AIRBORNE Dear Sir/Madam: Attached for your information please find a copy of a summary of a report on a Lifespan Oral Carcinogenicity Study of vinyl Chloride in Rats which we recently received and which I discussed with David Williams on Tuesday, October 2, 1984. This study was conducted in Europe by Civo Institutes TNO and was sponsored by verband Kunstofferzeugende Industrie E.V. (VKI). It is our understanding from VKI that the EPA will soon be receiving a copy of the final report. We do not have a copy. Upon review of this summary, we have been unable to determine whether this study presents any substantial risk information under the EPA's Statement of Interpretation and Enforcement Policy. 43 Fed. Reg. 11110 (March 16, 1978). It appears from the minimal data presented in this summary that the study is corroborative of effects already documented in the scientific literature. Sincerely, 517/636-0933 Attachment bcc: F. D. Hoerger, 2020 WHDC H. Schumacher, Horgen SUMMARY 1. The oral carcinogenicity of vinyl chloride monomer (VCM) was examined In a lifespan atudy (149 weeks) with five groups of Ulster rats, each consisting of 100 males and 100 females, except for the top-doss group which comprised 30 sales and 30 females. VCM was administered by In corporating polyvinyl chloride (FVC) powder with a high VCM content Into the diet. The diet vaa provided dally for a period of 4 consecu tive houra, whereas food was withdrawn during the other 20 hours. The use of this vsy of oral VCM administration resulted In the following exposure levels) 0 (control), 0.014, 0.13 and 1.3 mg VQI/kg body veight/day. An extra control group of 100 rsts/aex was housed In a separate room. Additional satalllte groups of 19 male end 10 female reca, each re ceiving the ease treatment'as che main group* were used for determi nations of glutathione levels In the liver after 9 and 18 months. Observations were msde of generel appearance mortality, growth, food Intake, thrombocyte count, prochrombln time, glutachionc levels in che liver, grose pethology and microscopic pathology of the liver and of all grossly visible tumours or presumable tumours In the abdominal Cavity, the glands of Zymbal and the mammary glands. 2. Ceneral health, behaviour, body weight and food Intake were not ad versely affected by the test substance. 3. In the second half of the experimental period, mortality in the extra control group was higher than in all other groups. This was most prob ably due to a high incidence of chronic reeplratory disease In the extra control group. In the final stage at the atudy, the mortality In the top-doee group was slightly higher than in the lower dose groups and the controls. 4. Thrombocyte count, prothrombin time end liver glutathione levels did not show treatment-related differencaa among the groups. 002461 1 * i,1 ji i; 3, A clearly higher Incidence of grossly visible, tumourous, liver nod ules was found In both males and females of Che cop-dose group chan In any of Ch ocher groups. Moreover, In females of Che top-dose group Che Incidence of hepatic cysts use considerably higher than In con trols. 6. Microscopic examination of Che liver revealed increased incidences of liver-cell polymorphism, hepatic cysts, foci of cellular alteration, neoplastic nodules and hepatocellular carcinoma* in tha cop-doia group as compared to the control group. Moreover, a hepatic angiosarcoma was found in one male and two females of the top-dose group, whereas no uch tumours were encountered In any of the other groups. The number of animals bearing foci of cellular alteration in tha liver wea also statistically significantly Increased in females of tha mid-dose group as compared to controls. In addition, In femalas but not In males, tha incidence of basophilic foci of cellular alteration in the liver was statistically significantly higher in both the lowend the mld-doae group than in the control group. 7. There was no evidence of VCM-feeding affecting the incidence of ab dominal mesotheliomas or the type and Incidence of mammary gland tu mours. Ho Zymbal gland tumour vaa found. 8. It vaa concluded that under the conditions of the present experiments - VCi at a level of 1,3 ng/kg body velght/day Induces neoplastic and oon-neoplaatlc changes in the liver of rats, " VO{ at a level of 0.13 ng/kg body valght/dsy may lead to more female rats bearing foci of cellular alteration in tha liver, - VCM at levels of 0.011 or 0.13 mg/kg body weight/day may result in an increased incidence of basophilic foci of cellular alteration in the liver of female rats, - 0.13 mg VCM/kg body waight/day Is a "no-obssrved"edverse--effectlevel' with raepect to the induction of tumours In rata. 33 99 03 O oro 07 fO ' v d3.285 9- Silk eatlaaclon baaed on chi reiulta of the preient rat scudy and Caking into account tha prudence of the linear model applied and a lener aertiitlvity of huaani to the catcinogenlc action of VCH in compariion with rati, iodieatea that the cancer riilc of a likely maximum oral daily intake of 0.1 fig VCH per penoa per day can be practically neglected. 33 U) O O to O) 03 v--1--i--> Meeting October 5, 1984 Present: C. Goodman, J. LeBeau, F. Hoerger, T. Torkelson, J. Gray, K. Beutel J. Gray advised those present that David Williams of EPA had called him at 5:00 P.M. on October 4, 1984 and told him that Cotruvo had been told nothing other than he would receive a study on vinyl chloride soon. Those present decided to submit the abstract (titled a sum mary) to the 8(e) office as a FYI. It was also decided to check with SPI to make sure the complete report would soon be submitted to EPA. We had information that VKI had sent the report to SPI. 10/11/84 R&S 002464