Document 6byE3pvdpwx96RR2XVJG77Bro

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 RECEIVED MAR Z 4 19SQ R. W. LASHER The attached material from the sponsors of Dr. Maitoni's VCM toxicity studies, reports on the paper given by Dr. Maltonl in Paris last November. It is presumed that Dr. Maltoni will cover much of this material at the 0SHA conference on March 20-21. Therefore, it will be Important to circulate it to those planning to attend this conference. Attachment UCC OOSggg ^veteeyti *rrv/ *m*v*w^** ' 'w ***'" Telephone Welwyn Garden 23400 (STD Code 07073) Tex 264251 From j Stafford Division Manager Health & Environment Protection To See belov Copies to Industries Limited Plastics Division Your rel. Our rel JS/SEW/CS0-16 Tel ext 3162 Date 3 March 1980 VCM - MALTONI The Maltoni VCM sponsors have agreed to the attached statement being sent today to national governments, onions, EEC and via AIME to the SPI in the USA and to the Japanese PTC 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 coamnmieation is in para k. In its early years, Maltoni*s work led us to the discovery of ASL in men highly exposed to VCM over a long period. Maltoni *s later work is of interest mainly to the scientific ooonuity who will be diseussing it for years. There is a limit to the amount of useful information which can be derived from i studies in the case of VOi we seem to have passed this limit some years ago. The only relevant and important studies now are those on man. J Stafford Circulation V F Madden J B M Sheaff D Bueknall G J Sleddon C N Levis D Parker V McMillan W G F Adams Oven Jones B Bennett D W Plaster F V Best A P Wright D Bryson K A Taylor M Vincent Mr D Robb Mr D C M Squirrel1 Mr T V 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 Hosier Mr A E H Williams Mr T L Phillips Dr J T Carter Dr D Scarisbriek Dr M Sharratt Mr W McMillan IkP Levis Mr B Hutchesson Dr A Holmes Walker Mr H Clayton Mr M J S Gibbons Dr D M Ferguson - UCC 005990 ageeed statement by the maltoni sponsors on the seven basic vcm experiments * (BT1, 2, 6, 9, 15, 11 & 27) 1 Introduction The long term project by Professor C Maltoni on tbe 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 Solray, 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 the e experiments and, in cooperation with a teem 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 presents! in extsnao 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. 9 2 Biological Assessment of the Results In Profesaor Maltoni's opinion regarding these animal experiments "the foil wing tumours should be given proper attention vis, extrahepatic angiosarcomas, hepatomas, Zymbal gland carcinomas, liver angiosarcomas, neuroblastomas, nephroblastomas, forestomach papillomas and nummary carcinomas. In oncological terms, the meaning of the results at the lowest doses stay be b tter evaluated by considering, not separately, bat together, tbe tumours found to be VTM dependent* Thus the following results should be considered: -- at 29 ppm - In 120 animals, 9 liver angiosarcomas, 4 Zymbal gland carcinomas and 1 nephroblastoma. at 10 ppm -- In 120 animals, 1 liver angiosarcoma, 2 extra--hepatic angiosarcomas and 2 Zymbal gland carcinomas. at lmff/Wg - ln 190 animal a, 3 liver angiosarcomas, 1 extra-hepatic angiosarcoma, 1 hepatoma and 3 Zymbal gland carcinomas. at 0.3tg/hg-In 130 animals, 1 liver angiosarcoma and 1 hepatoma.** In addition, it Is worthwhile emphasising that none of the previously cited tianoura have been observed at 5pi by inhalation and 0.03mg/kg by ingestion. 5 Statistical Assessment of the Results A multi-disciplinary working group was set up by the sponsors for the in-dopth quantitative analysis of tbs 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 murinary gland in females. The survival of the rats decreased as a function of VCM concentration. A clear correlation could b established ucc 005991 -2- between excess mortality and tumorigenic power of VCM but the excess mortality cannot be explained only by the development of cancers at the higher dose levels. Correspondence analysis between tumours and doses showed that two major opposing factors may explain tumour distribution vizi (i) the differential susceptibility of the target organs to the carein genic 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 *xperimental data. This study also illustrated the problems of extrapolating to untested doses and from species to species. 4 In conclusion The publication of the proceedings of the iO/ll/79 laris 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 cimmunity of the Maltoni and other animal studies on VCM. The Maitool 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 UCC 005992