Document 9JDvx6gLw9rQbE73jJBRE7OgR

* .. `1 FILE copy ioia MANUFACTURING CHEMISTS ASSOCIATION 1825 CONNECTICUT AVENUE, N.W. WASHINGTON, D.C. 20009 (202) 483-B128 pril 17, 1974 To: TECHNICAL TASK GROUP ON VTNYL CHLORIDE RESEARCH Subject: Report on Conference with Industrial BIOTEST Laboratories. April 15. 1974 Gentlemen: As a result of the telephoned information received by MCA from Industrial BIO-TEST personnel last week, a conference at the Northbrook, Illinois offices of IBT was set up at which an oral status report on the chronic in halation studies with vinyl chloride was presented to MCA, industry and federal agency representatives. Those in attendance, and their affiliations, are shown below: Z. G. Bell, Jr. A. S. Cummin E. J. Fairchild J. W. Goode D. E. Gordon W. D. Harris M. N. Johnson, M.D. Flynt Kennedy M. L. Keplinger R. J. Kociba H. L. Kusnetz D. V. Lassiter W. E. Rinehart W. M. Smith J. F. Stara T. R. Torkelson R. N. Wheeler B. M. G. Zwicker R. F. Blewitt A. C. Clark K. D. Johnson PPG Industries, Inc. Borden, Inc. NIOSH Industrial BIO-TEST Laboratories Industrial BIO-TEST Laboratories UNIROYAL, Inc. The B. F. Goodrich Company Continental Oil Company Industrial BIO-TEST Laboratories The Dow Chemical Company Shell Oil Company OSHA Ethyl Corporation Air Products & Chemicals, Inc. U. S. Environmental Protection Agency The Dow Chemical Company Union Carbide Corporation B. F. Goodrich Chemical Company MCA MCA MCA 1193 ar;;,.*- v O. i'i,^ eJ?v r.;-''& 2- - ^-ry-vi' *;r .- ,.y.. **; ^ - - .,* 5rt.>V''1S^.a^?*'^*fj};'tt,fr'\'>~,,"/`'-f'c%>. J-/agr? .:: &1 r. - Dr. Goode first presented the mortality data and gross observations, and then Dr. Gordon described the pathology observed in the mice. The data, as presented, ars shown in the attached tables. There are apparent discrepancies between the total mortality data and the detailed listing of recent deaths.- These will be re solved. No test-related pathology has yet been noted in any animals other than mice. Dr. Fairchild, of NIOSH, reported that Dr. David Rail, of HEW, had appointed a committee to coordinate departmental toxicology and related programs, and that under this committee there has been named a subcommittee to develop a "white paper" on guidelines for research to determine "socially acceptable" levels of risk. A report from this subcommittee, which will cover both philosophical and statistical considerations, is expected in the next few weeks. Dr. Stara expressed the view that the vinyl chloride problem presented industry with a unique opportunity to seek to demonstrate a "no effect level" of a human carcinogen with a sensitive animal model of well-documented validity. Dr. Lassiter expressed a guarded judgment that the mouse data reported by IBT would not lead OSHA to modify the emergency temporary standard, but that it might well cause OSHA to accelerate the rule-making process for the development of a permanent standard. Dr. Lassiter also reported briefly on the retrospective morbidity and mortality studies being conducted by NIOSH/CDC at nine or ten locations (six companies) around the country. No epidemiological data were presented. In an afternoon session of the Research Coordinators, it was agreed that the exposure of the mice in the present project should be terminated at nine months, but that exposures of both rats and hamsters should proceed for the initially-planned twelve months. It was further moved, seconded and carried that the chairman appoint a group to begin investigating the cost and availability of facilities of new experiments to be con ducted at lower levels of exposure, with larger groups of animals. He was asked specifically to seek to encourage the National Center for Toxicological Research, at Pine -ftiVIDO Bluff, Arkansas, to offer to-undertake such a program. Details of the test protocol are to be left open until after the Rail committee makes its report available. The Research Coordinators asked MCA to call a meet ing of the Technical Task Group on Vinyl Chloride Research as soon as the report of Tabershaw-Cooper Associates on their epidemiological study reaches them. A copy of the MCA news release reporting the Industrial BIO-TEST mouse data has been sent to you in this morning1s mail. Sincerely, KDJ:mb Kenneth 0. Johnson, Ph.D. Secretary Technical Task Group on Vinyl Chloride Research Tables Attached cc : Mr. A. W. Barnes D. P. Duffield, M.D. Dr. Tiziano Garlanda Vinyl Chloride Management Contacts ocW 1111 TABLE 1 Mouse Mortality Data DATE Controls FM February 10, 1974 28 GROUP TI TII FM FM 6 26 24 Till FM 78 April 12, 1974 5 11 9 31 13 7 13 18 tW 11! 2 -- - '>-". A, .. --XL"*'**-' * !)ttduAh(jal- Bt 3 - TEST JjgJjou'jut&vueA, 3m. i8io Frontage road * TABLE XI NORTHBROOK. Ill IMOIS 60062 Summary of Tumors in VinvI **hloride Exposed Mice II3T Number 603-03222-MCA Group, Animal No. , Sex Histopathologic Finding s Date of Death X -X 102 3 Male 1110 Fe ma le 1 1 19 Female 1200 Female Lung Liver AA (s)*' HS ()** AA (s), Metastatic . Skin Tumor HS (s) Metastatic Skin Tumor Skin EC (para-aural) 3-20-74 3-24-74 EC & MC+ (Femoral region) 3-30-74 T-11 1347 Female 1309 Female 1889 Male 1382 Female 1350 Female 1299 Female T - III 1538 Female 1532 Female 1562 Female 1598 Female 1405 Male 1494 Male 1574 Female 1531 F emale 1588 Female 1593 Female 1505 Female 1565 Female 1409 Male 1543 Female 1544 Female 1546 Female 1535 Female 1432 Male 1477 Female * Metastatic Skin Tumor I-IS (s) AA (s) HS HS (s) AA (s) HS (s) AA (s) AA (s) AA (s) AA (s) AA (s) AA (s) AA (s) AA (s) HS (s) HS (s) HS (s) HS (s) HS (s) IIS (s) HS (s) AA (s) AA (s) AA (s) AA (s) AA (s) AA (S) AA (s) HS (s) HS (s) HS (s) HS (s) HS (s) HS (s) HS HS (s) Aa (s) AA (s) HS (s) AA (s) HS (s) Metastatic Skin Tumor? EC( Abdomen) 3-5-74 3-18-74 3-25-74 4-2-74 4-5-74 EC & MC (Inguinal Region) 4-9-74 LS<> 3-6-74 3-7-74 3-8-74 2-25-74 3-22-74 3-22-74 EC h MC (Femoral region) 3-23-74 3-25-74 3-30-74 4-3-74 4-3-74 . 4-5-74 4-5-74 4-5-74 MC (Axillary region) 4-5-74 4-7-74 4-8-74 EC (Para-Aural) MC (Abdomen) EC( Pelvic region) 4-9-74 ^ U13 anHUHNHnBMnsnMwanBnnHHn^BH^HHMMHHEnBBHaniH ; * i , . Group T-I T-II T-III r,tg?reg;riT;ra.iRy> --raflaa.-^.,,, ,,/..r.,a^.Y,,, ..-*** *..i:.-..:^ TABLE III 9nduAi/Lial BIO - T E S T JlaJy^aicyu^, 9m. 1810 FRONTAGE ROAD NORTHBROOK. ILLINOIS 60062 Summary of Mortality & Tumor Data Among Vinyl Chloride Mice IBT Number 6u^-0ZZZZ (MCA) No. Mortalities with Neoplasms Location oi Tumors " Lung Liver Skin Metastasis -> Lu 4(1 Male, 3 Females ) 2(50%) 2(50%) 2(50%) 2 6 (1 Male, 5 Females) m 19 (4 Males, 15 Females) 3(50%) 4(66. 7%) 2(33%) 1 17(89.5%] 17(89.5 %) 3(15. 8%) Key to Symbols * Alveologenic Adenoma of J ung (AA) ** Hemangiosarcoma of Liver ( HS) *** Epidermoid Carcinoma of Skin (EC) + Mammary Carcinoma of Skin (MC) a Lymphosarcoma of Thymus (s) Multiple tumors of indicated type 'iW H| 4 j) INTERIM RESUITS OF EXPOSURE OF RATO, HAMSTERS AND MICE TO VINYL CHLORIDE M. L. J. W. D; E. and J. C. Keplingcr, Ph.D., Goode, Ph.D., Gordon, D.V.M., Ph.D. Calandra, M.D., Ph.D. Industrial Bio-Test Laboratories, Inc. Northbrook, Illinois The following data are partial results of a study in progress at the Industrial Bio-Test Laboratories, Inc. The studies are being coordinated .for sponsoring companies by the Manufacturing Chemists Association. The data are very incomplete but because of their significance were first presented to EPA, NIOSH and OSHA on April 15, 1974. In this study which was designed to complement Maltoni's studies, 100 rats, hamsters and mice of each sex (600 total per exposure group) are being exposed to either 0, 2500, 200 or 50 ppm vinyl chloride vapor 7 hours per day 5 days per week. Mice will be exposed for 9 months and kept for an additional 9 months. Rats and hamsters will be exposed for 12 months and kept for an additional 12 months. The rats are COBS Charles River; mice are CDI Swiss Charles River; and the hamsters are Golden Syrian from the same source. Food is removed during exposure, water is present and no bedding is used at any time. Moribund and dead animals (when possible) receive gross autopsies and arc photographed. The major organs of all animals are fixed for histological examination. Only the tissues from a few animals have been examined so far. The table shows the results to date (about 8 months exposure). LoV 11(5 twmsssss^i^*' Note that no direct numerical comparisons can bo made with tho control groups as they have not been selected in the same way. Only mice with tumors have been examined in the exposure groups. No tumors have been observed grossly as yet in any of the control mice. In addition to the tumors in mice a few tumors have been observed in rats and hamsters but because of autolysis the diagnosis at this time must be considered tentative. At this time it appears that angiosarcomas may have been observed in one male hamster and one male rat exposed to 2500 ppm and in one female rat exposed to 200 ppm. No tumors have been observed in rats or hamsters exposed to 50 ppm but one male control was found to have a dermal fibroma. These tentative data need to be confirmed and will be reported in detail when the study is completed. 1 6r\W ? t a