Document Rj8BXwZqox3bGegNqypwKj5O7

The Society of th# Plastic* Industry, Inc. 355 Lexington Avenue New York, New York 10017 (212) 573 9400 March 17, 1980 TO: FROM: THE PVC SAFETY GROUP i> JOHN R. LAWRENCE U TECHNICAL DIRECTOR ' ' Sj / RE: MALTONI'S VCM TOXICITY STUDIES \ 3 MAR 2 4 1980 R. W. LASHER **Oj *l> "Ann 1380 The attached material from the sponsors of Dr. Maltonl'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 UCC 005993 'ii':!p!!rp !:,ir:;!TF'^lFPTFiFpFliFiFin! 1;";i ^ :i 'll!l WMwyn Gartw Cay Hmumaw au inu Teleohone Welwyn Garden 23400 (STD Code 07073) Telex 264251 From J Stafford Division Manager Health &. Environment Protection To See below Copies W Industri s Limited Plastics Division Your ref. Our rel JS/SEW/DSO-16 Tel ext 3162 Date 3 March 1980 VOi - MALTONI The Maltoni "VCM sponsors have agreed to the attached statement being sent today to national governments, anions, EEC and via AFME to the SPI in the USA and to the Japanese PVC Association. This is not a general press release bat it is information which should be shared with relevant employees at your next round of consultative meetings. The key to the eemranication is in para k. In its early years, Maltoni's work led us to the discovery of ASL in men highly exposed to VQi over a long period. Maltoni's 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 VQi we seem to have passed this limit some years ago. The only relevant and important studies now are those on man. r J Stafford J? i f Circulation V F Madden J B M Sheeff D Buclmall 6 J Sleddon C N Lewis 0 Parker V McMillan V G F Adams Owen Jones B Bennett 0 V Plaster F V Best A P Wright D Bryson X A Taylor M Vincent Mr G Hallybone Mr D Robb Mr D C M Squirrell Mr T W Moffitt Dr X S Williamson Dr G Paddle Dr D P Doffield Mr D Bartholomew Dr A A B Swan Dr 1 F B Purchase Mr R Hards Mr B Haaler Mr A E H Williams Mr T L Phillips Dr J T Carter Dr D Searisbrick Dr M Sharratt Mr W McMillan IkP Lewis Mr B Hutehesson Dr A Holmes Walker Mr H Clayton Mr M J S Gibbons Dr D M Ferguson - ucc 005994 :i` I: :. I jUffipEn STATEMENT BY THE MALTONT SPONSORS ON THE SEVEN BASIC VCM EXPERIMENTS (BT1, 2, 6, 9, 15, 11 & 27) 1 Intr duction 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-Poulene, Montedison and ICI. The laboratory work was started in 1971 end ended in 1977* Since 1977, Protestor 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 lesion* 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. f 2 Biological Assessment of the Results In Professor Maltoni's opinion regarding these animal experiments ''the following tumours should be given proper attention vis, extrahepetie 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, k Zymbal gland carcinomas and 1 nephroblastoma. at 10 pm - In 120 animals, 1 liver angiosarcoma, 2 extra-hepatic angiosarcomas and 2 Zyabal gland carcinomas. at lmg/kg - In 150 animals, 3 liver angiosarcomas, 1 extra-hepatic angiosarcoma, 1 hepatoma and 5 Zyabal gland carcinomas. at 0.3mg/ka-In 150 animals, 1 liver angiosarcoma and 1 hepatoma." In addition, it is worthwhile ophaslslng that none of the previously cited tumours have been observed at 5pp* by inhalation and 0.03mg/kg by ingesti n. 3 Statistical Assessment of the Results A multi-disciplinary working group was set up by the sponsors for the in-dcpth 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 vis, 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 ucc 005995 betv en excess mortality and tumorigenic power of VtM but the excess mortality cannot be explained nly by the development of cancers at the higher d se levels. Correspondence analysis between tumours and d ses showed that two major opposing factors may explain tumour distribution vis: (i) the differential susceptibility of the target orgaim to the carcinogenic effect of VQf (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 10/13/79 Paris meeting and other related papers will no doubt lead during the course of the next few years t the comprehensive discussion and comparative assessment by the scientific cotmnunity of the Maltoni and other animal studies on VCM. The Maltoni studies have provided much useful information especially in the early years| the later experiments have highlighted the problesis of evaluating low d se animal experiments. . 26 February 1980 ucc 005996