Document bkQX0OwrN8qqgB5wzpMrX8ng

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 MAR o 8 $35 g (/> o oro U1 <0 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 DOW 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, Attachment bcc: F. D. Hoerger, 2020 WHDC H. Schumacher, Horgen SUKHASf X. The oral carcinogenicity of vtnyl chloride monomer (Vd) un examined In a lifespan study (149 weeks) with five groups of Ulster rata, each consisting of 100 salaa and 100 females, except for the top-dose group which comprised JO males and SO females. VCM was administered by In corporating polyvinyl chloride (FVC) powder with e high VCM content Into the diet. The diet wee provided dally for a period of 4 consecu tive hours, whereas food was withdrawn during the other 20 hours. The use of this way of oral VCM administration resulted la the following exposure levels: 0 (control), 0,014, 0.13 snd 1.3 mg VCM/kg body velght/dsy. An extra control group of 100 rata/sex was housed In a aaparata room. Additional sstslllte groups of IS male and 10 female rets, each re ceiving the same treatment"as che main groups were used for determi nations of glutachlone levels In the liver after 9 and 18 months. Observations were mads of general appearance mortality, growth, food Intake, thrombocyte count, prothrombin time, glutathione levels In the liver, gross pathology snd microscopic pathology of the liver and of all grossly visible tumours or presumable tumours In the abdoolnel cavity, the glands of Zynbal snd the mammary glands. 2. General health, behaviour, body weight snd food Intake were not ad versely affected by the test subatance. 3. In the second half of the experimental period, mortality in the extra control group waa higher than In all other groupa. This was most prob ably due to a high Incidence of chronic respiratory disease In the extra control group. In che final stage of che study, the mortslity la the top-dose group was slightly higher than in the lower dose groups end the controls. 4. Thrombocyte count, prothrombin time and liver glutathione levels did not show treetment-telated differences among the groups. R&S 002461 J. A clearly higher incidence of grossly vlill1*. tumourom, liver nod ule* vt found In both melee end female* of the top-doac group then in any of Che ocher groups. Moreover, In female* of Che top-dose group Che Incidence of hepatic cyec* we* considerably higher then In con trol*. 6, Microscopic examination of the liver revealed Increased Incidences of liver-cell polymorphism, hepetlc cyste, foci of cellular alteration, neoplaecic nodules end hepatocellular carcinoma* In Che top-dose group a* compared to the control group. Moreover, e hepetlc angiosarcoma was found in one mala and tvo female* of the top-dose group, whereas no such tumours were encountered in any of tha ocher groups. The number of animal* bearing foci of cellular alteration In the liver wmm also statistically significantly Increased in females of the mid-dose group aa compared to controls. In addition, tn females but not in mains, the incidence of basophilic foci of cellular alteration In the liver was statistically significantly higher la both the lowand the mid-dose group than in the control group. 7. There was no evidence of VCM-fesding affecting tha incidence of ab dominal mesotheliomas or the type and incidence of mammary gland tu mours. No Zymbal gland tumour was found. 8. It was concluded that under the conditions of the present experiment: - VCH at a level of 1.3 mg/kg body weight/dsy Induces neoplastic and non-neoplastlc change* in tha liver of rats, - VCM at a level of 0.13 ag/kg body weight/day may lead to more female rata bearing foci of cellular alteration In the liver, - VQt at levels of 0.014 or 0.13 mg/kg body weight/day may result in sn increased incidence of basophilic foci of cellular alteration in Che liver of female race, - 0.13 mg VCM/kg body weight/day is a "no-observed--adverse--effectlevel" with respect to the Induction of tumours In rats. 33 99 U) o oto * O to V 33.235 6 9. Rlak estimation based on the results of the present rat study and taking Into account th* prudence of the linear model applied and a leaser aenattlvity of human* to the carcinogenic action of VCM In companion with rata. Indicates that the cancer risk of a likely maximum oral dally Intake of 0,1 pg VCM per peraoa per day can be practically neglected. R&S 002463 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