Document a4GK7BvbdJYYnnVGpzeXLB7VB

The Society of the Plastics Industry, Inc. 355 Lexington Avenue New York, New York 10017 (212) 573 9400 March 17, 1980 TO: THE PVC SAFETY GROUP FROM: JOHN R. LAWRENCE TECHNICAL DIRECTOR * RE: MALTONI'S VCM TOXICITY STUDIES The attached material from the sponsors of Dr. Maltoni's VCM toxicity studies, reports on the paper given by Dr. Maltoni in Paris last November. It is presumed that Dr. Maltoni will cover much of this material at the OSHA conference on March 20-21. Therefore, it will be important to circulate it to those planning to attend this conference. Attachment eiephone Welwyn Garden 23400 (STD Code 07073) Telex 264251 From To J Stafford Division Manager Health & Environment Protection See below Copies to II IUUOU ICO Limited Plastics Division Your ref. Our ret JS/SEV/DSO-16 Tel ext 3162 Date 3 March 1980 VCM - MALT0NT The Maltoni VCM sponsors have agreed to the attached statement being sent today to national governments, unions, EEC and via AfME to the SPI in the USA and to the Japanese PVC Association. This is not a general. press release but it is information which should be shared with relevant employees at your next round of consultative meetings. The key to the communication is in para 4. In its early years, Maltoni's work led us to the discovery of ASL in men highly exposed to VCM over a long period. Maltoni1s later work is of interest mainly to the scientific community who will be discussing it for years. There is a limit to the amount of useful information which can be derived from animal studies and in the case of VCM we seem to hove passed this limit some years ago. The only relevant and important studies now are those on man. J Stafford Circulation Dr V F Madden Mr J B M Sheaff Mr D Bucknall Mr G J Sleddon Mr C N Levis Dr D Parker Mr W McMillan Dr W G F Adams Mr Owen Jones Dr B Bennett Dr D W Plester Dr F W Best Dr A P Wright Dr D Bryson Dr K A Taylor Mr M Vincent w_ n W-11..J. ______ Mr D Robb Mr D C M Squirrell Mr T W Moffitt Dr K S Williamson Dr G Paddle Dr D P Duffield Mr D Bartholomew Dr A A B Swan Dr I F H Purchase Mr R Hards Mr B Hasler Mr A E H Williams Mr T L Phillips Dr J T Carter Dr D Scarisbrick Dr M Sharratt Mr W McMillan H-P Levis Mr B Hutchesson Dr A Holmes Walker Mr H Clayton Mr M J S Gibbons ' Dr D M Ferguson - CCR 000011345 AGREED STATEMENT BY THE MALTONI SPONSORS ON THE SEVEN BASIC VCM EXPERIMENTS (BT1, 2, 6, 9, 15, 11 & 27) Introduction The long term project by Professor C Maltoni on the carcinogenicity assessment of VCM has comprised a series of integrated experiments to study the effects of VCM administered by different routes, at different concentrations and for different periods on animals of various species, strain and age. This work was initiated and sponsored by Solvay, Rhone--Poulenc, Montedison and ICI. The laboratory work was started in 1971 and ended in 1977* Since 1977, Professor Maltoni has been processing and analysing the vast amount of histological material derived from these experiments and, in cooperation with a team of statisticians from the four sponsoring companies, has been classifying and codifying all the identified pathological lesions to make the data amenable to computer treatment. The data thus derived have been analysed statistically in a rigorous manner. The results of this work were presented in extenso with all the methodological, biological and statistical details in a meeting held by the Chemical Carcinogenesis Club (Club de Cancerogenese Chimique) at the Curie Foundation (Fondation Curie) in Paris on 10 November 1979 The proceedings of the meeting will be published in full at the earliest possible moment. Biological Assessment of the Results In Professor Maltoni*s opinion regarding these animal experiments "the following tumours should be given proper attention viz, extrahepatic angiosarcomas, hepatomas, Zymbal gland carcinomas, liver angiosarcomas, neuroblastomas, nephroblastomas, forestomach papillomas and mammary carcinomas. In oncological terms, the meaning of the results at the lowest doses may be better evaluated by considering, not separately, but together, the tumours found to be VCM dependent. Thus the following results should be considered:-- at 25 ppm - In 120 animals, 5 liver angiosarcomas, 4 Zymbal gland carcinomas and 1 nephroblastoma. at 10 pnm -- In 120 animals, 1 liver angiosarcoma, 2 extra--hepatic angiosarcomas and 2 Zymbal gland carcinomas. at lmp/kg -- In 150 animals, 3 liver angiosarcomas, 1 extra--hepatic angiosarcoma, 1 hepatoma and 5 Zymbal gland carcinomas. at 0oPe/kg-I11 150 animals, 1 liver angiosarcoma and 1 hepatoma." In addition, it is worthwhile emphasising that none of the previously cited tumours have been observed at 5ppo by inhalation and 0.03mg/kg by ingestion. Statistical Assessment of the Results 000011346 A multi-disciplinary working group was set up by the sponsors for the in-depth quantitative analysis of the data. A statistical evaluation of all the available results from the above seven animal experiments has led to the conclusion .that VCM induces a carcinogenic response in the following organs viz, the Zymbal gland, liver, kidneys, brain and perhaps the mammary gland in females. The survival of the rats decreased as a function of VCM concentration. A clear correlation could be established -2- between excess mortality and tumorigenic power of VCM but the excess mortality cannot be explained only by the development of cancers at tbe higher dose levels. Correspondence analysis between tumours and doses showed that two major opposing factors may explain tumour distribution viz: (i) the differential susceptibility of the target organs to the carcinogenic effect of VCM (ii) an antagonistic factor (early mortality) which at too high a dose inhibits the manifestation of certain tumours. Several models of dose--effect relationships fit the experimental data. This study also illustrated the problems of extrapolating to untested doses and from species to species. ^ In conclusion The publication of the proceedings of the 10/ll/79 Paris meeting and other related papers will no doubt lead during the course of the next few years to the comprehensive discussion and comparative assessment by the scientific community of the Maltoni and other animal studies on VCM. The Maltoni animal studies have provided much useful information especially in the early years; the later experiments have highlighted the problems of evaluating low dose animal experiments. 26 February 1980 CCR 000011347 Ponca City, Oklahoma May 15, 1980 REPORT OF MEETING VCM Technical Panel - May 14, 1980 - Washington, D. C. CMA called a meeting of the VCM Technical Panel on May 14, 198O to discuss the results from a pathological examination of all animal brains saved from the Industrial BioTest Laboratory (IBT) VCM exposure study. The action steps are listed below; nothing was found to change the earlier conclusions from the study. The enclosed reports by Experimental Pathology Laboratories, Inc. and Bob West Associates, Inc. will be sent to Frank D. Kover of the EPA per the earlier CMA mailing of March 19, 1980. The pathology report concludes the IBT animal exposure tests provide only qualitative information due to the shortcomings of the experimental procedures, and do confirm Maltoni's data. CMA will advise Kover that no additional work is contemplated. The West report, a thir*d party expert, concludes the IBT study was con ducted in an extremely sloppy fashion and provides results of a qualitative rather than a quantitative nature. There are several d i screpancies noted which may be of significant value to the CMA lawyers regarding recovery of money from !BT for work improperly performed. A complete set of reports from the March 19, 1980 and May 16, 1980 mail ings to Kover will be provided OSHA, NIOSH, NCI, FDA, CSPC, and Kostel of EPA with a cover letter indicating "for their information, the enclosed reports have been sent to Frank D. Kover of EPA." The panel was also advised CMA has been sued for $2 MM damages in Louisiana by an individual who was exposed to acrylonitrile (CH2=CH-CN) and then was diagnosed as having cancer. CMA is purportedly to blame because CMA with held data regarding the carcinogenic nature of vinyl chloride (CH2=CH-C1) in 1973- It is a preposterous situation but nonetheless CMA will be involved and have retained the New Orleans firm of Liskow and Lewis (Barry St. John) CMA counsel estimated the court costs could approach $100 M and CMA will ask member companies represented on the VCM Panel to provide the necessary financial support. General Counsel for each of the member companies will receive a mailing soon with several documents related to this case. I will advise Andy McColpin by phone of the general situation to minimize surprising top management. F1yn l Nenneay Manager Chemicals Research Division 1m Distribut ion: J.J.Hal 1-C.L.Whetstone-W.CK Brodd1e-V.Moore CCR 000011348