Document 5bEpVkJ5OMyyED0kKD1R55Ev8

JED CHEMICAL CORPORAT MEMORANDUM l CONFIDENTIAL MEMO TO: Mr. J C. Fedoruk ' Mr. A P. McGuire FROM: W. A. Knapp November 20, 1972 RECEIVED \m 2 0 1972 uEGAl DJ2L There was considerable confusion at this meeting as to agreement to retain confidentiality of the data. When Dr. Harris arrived in Italy, it was discovered that Mr. Best's (MCA) agreement with Mr. Lmdsell (ICI, Director of European Monomer Group) was not satisfactory. Consequently Dr. Harris was showrn the equipment and given only the test protocol, not the results. The protocol is attached. At our meeting, a few wanted limitations placed on confidentiality (particularly as it may relate to disclosure requirements in Food Additive petitions) but most thought disclosure restrictions a detail, difficulties concerning which were very unlikely to occur. After rather weak reassurances, Mr. Don M. Elliot (ICI) decided that he would take it upon himself to disclose what he knew. He requested that no notes be taken (which request was honored) so that summary of results attached may be subject to some inaccuracies but is generally correct. Further, with respect to confidentiality of data, it is reported that a Dr. Caputo at the Univ. of Florence (a cohort of Dr. Viola?) will present a continuation of Dr. Viola's results at a meeting in 1974 w-hich will thereby reduce confidentiality of results. Ap-parently, Dr. Viola's presentation at Houston about 2 years ago was made without Solvay's permission that Europeans are very sensitive about disclosure conditions. The major disclosure is that substantial numbers of tumors were formed at 10,000 ppm and single tumors at concentrations as low as 500 and 250 ppm. It is to be noted that exposures were for one year and are now completed except where replacements were made for early deaths. How many such replacements were necessary was not clear. The fact is exposures have been completed and animals are now being retained awaiting death from whatever cause. One thing not clear in the protocol is whether food and water for the AST 000013788 Mr. J. C. Fedoruk Mr. A. P. McGuire 2 November 20, 1972 animals remained in the cage during the exposure period; the animals were apparently not removed from exposure chambers between exposures. It is the feeling of the writer that absorption on fur and subsequent licking plus solution of gas in water or in fat component of food can be the greatest source of intake and must >e monitored if results are to be meaningful. Many questions with respect to protocol and results could not be answered. To the most knowledgeable people, the results were sufficiently disconcerting to prompt immediate reconsideration of the U.S. Industry Program. Accordingly, the Task Force was to meet directly following our session. Among things to be reconsidered are metabolism studies and tne epidemiology deleted from first program because of cost. Recipients of this memorandum are reminded that by agreement with the European Group, we will exert every reasonable effort to retain contents in strict confidence within company personnel. To this end, it is requested that disclosure not be made beyond recipients of this memorandum without prior notice to the writer. Only this will reasonably retain the strict confidentiality required. cc: Mr. W. S. Ferguson AST 000013789 y*nvl Chloride Monomer - European Project Protocol Animal species: Sprague-Pawley rats of thoroughly documented pedigree especially with regard to cancer incidence in various tissues. Dosages: 10,000, 6,000, 2,500, 500, 250, and 50ppm. 65-55 animals per group. Time of exposure: U hours real rime/day, 5 cays per week for one year. Animals are observed until natural death. Professor Maitoni feels that one year is better than longer exposure since toxicity may kill animals before cancer develops especially at higher dosages. Animal housing and handling: All animals cf one group were in one chamber which had three levels with two cages of 10 or more animals each at the beginning of the experiment. Of the orig inal 577 animals at the start cf exposure, 275 have died of natural causes. There is a separate mixing device for each chamber. The VC air mixture is fed through a large pipe into each of the three levels of the chambers. A gas sam ple tube leads from each metering device to a central gas chromatograph. Periodic samples are also taken from the chambers to maintain the dosage very close to the desired levels. Records are complete and neat, professor Maltoni is intimately acquainted with every phase cf the work. Three Fh. D's work or, this nnase.cf . . v* * the work. A stancarc bsiancec iaborarcry/is supplied by a feed company according tc his for-_ Observation and pathology: Weighed every two weeks. Observed individually several times daily. Careful clinical examinations weekly. On death complete autopsy. Those with tumors are x-rayed-whole body by a special technique which shows cancerous tissue. All organs examined carefully. Professor Mai coni' personally reads all slides. Color photos are made cf tumors. European Project Sponsors : Imperial Chemical Industries Solvay ct Cle Montedison Rhone-Progil Research Investigator in charge Professor Cesare Mai coni Institute Di Ancologia Bologna, Italy AST 000013790 Vinyl Chloride Monomer Inhalation Study Cone.(ppm) No. at start/ surv, G* K* L * Vinyl acetate Vinyl chloride 2,500 10,000 6,000 95/22 70/30 7/3-rlm 3/1+lm 2 - 2,500 500 70/45 70/50 0 1+lm? 4 250 70/50 1 - 50 70/50 0 - 0 70/50 0 V 8 (total), remembe distrib Exposure 4 hrs/day, 5 davs/wk for one year animals now 72 wks. old . animals die * Gross and micro scopic autops y made as G* - ceruminosa gla nd in ear K* - kidney L* - liver AST 0000i379i