Document O3wDBnyNDZjBnVMxk1b9gJkoX

December 3, 1971 Mr. I. I. VfeMln Mnlon Cirbld* Oaryontioi 437 McCorkle Amue, 8.W. South Charleston, VMt YirgitU Dear Sick, Vursnant to the MCA meeting of November IS on vinyl chloride, the following are writer's questions and suggestions concerning the proposed sassfacturer-sponsored toxicological research. (1) After I left the seeting, It suddenly occurred to se to question the diagnosis of the lesions as cancers vs. tumors. X preetaee the evaluation is conclusive but, if it is not, sous part of the proposed protocol should include a recovery period to note whether the lesions regress. (2) It Is presumed that no husan tunor has yet been attri buted to fCM, hot it would appear to be worthwhile to review the working population that was used by the Pnlversity of Michigan for study of acrooeteolysis. This certaisly includes the sost highly exposed popu lation and, if no tunors exist here, it can be argued that huaaa experience, if of reasonable magnitude, should take precedence over animal studies. It is conceded that thin lesion was sot sought is Dr. Oilman's study hut, fros the available records, it sight be sasier to review this population than another couplet ly nee one. X as thinking of a limited edipesialogical study, possibly at n substantially lowsr cost. <3) Is the matter of amalysim of XDC or acetylene derived samples of TCM, we do not expect to discover known carcinogens, however, it does sees desirable to know whether there are any gross differences in the sampl s used by Dr. Viola and those to be used here. Certainly the 25 (or 29) impurities mentioned are not all present la equal quantities eves if made by the same process, and X suspect that process dlffsrence nay be substantial. At least we should know tbs variation which can be ex pected and he certain that the materia1 used is within limits set by analysis of at least six samples fros ach process, To be certain that sample impurities do not reveal proprietary process secrets of any sanufactur r, MCA could act as a clearing house for analyses. A look at tbs analyses doss not necessarily sean that the A.SI 00001646 r. K. V. Vheeler texlcelegy project need bo delayed. Sack manu facturer should bo able to report analyses of fee batches vithia one month and, if no najor deviations appear which are of Major concern, stndy could start 1--rnllattl y till one sanplo (single unit tank car) of fOl be need, or will it be used Iron "one-ton" or anallor cyllndorsT (4) Vo have no serious objection to the exposure protocol but would prefer one aon-rodoat species even If numbers of aaiaals (possibly dogs or Monkeys) were substantially lower in aanber. Ve realise that statistical result will not be as significant, but tbs opportunity to observe a cosplstsly dIffareat species where net&bollc pathways say bs substaatlally different would appear to justify tbs statistical sacrifice, (5) Mutagenicity and teratogenicity were Mentioned briefly nt tbs sestlag, bat wo eaa recall no declaion as to whether such studies would ho lncledod. Ve think tosts in this area sight bs desirable hut have no strong feeling that they should bo included in thin protocol. Dr. Legator of FDA hoHaves that nutagenicity say be predictive of carcinogenicity. In view of the lack of any similar visible lesion in a substan tial exposed busan populatloa, ws doubt that regulatory agencies in this country will take any precipitous actios before confirming tb results bore. Ve do believe that nasplos of food-wrapping films should be tented for nigration into solvents simulating food to dis cover levels which nay bs expected frea reasonably standard FTC formulations. Ve will be happy te cooperate with the industry group in this natter of safety and health ef esployees mod public. iscerely yours. V* A. Knapp Toxicology-Consultant VAK:pb cc: Dr. Dorman G. Vbite Shell Chemical Company AS1 000016466 Dr. Benjamin I. G. Zwicker B. F. Goodrich Chemical Conpaay bcc: Mr. J. C. Fedoruk, DAB-2 Mr. K. K. Sheth, Plastics Division, Painesville, Ohio