Document O3NN4oKq8JdGDvbGb76qazbJe

' .IED CHEMICAL CORPORAT I MEMORANDUM CONFIDENTIAL MEMO TO: Mr. J. C. Fedoruk Mr. A. P. McGuire FROM: W. A. Knapp November 20, 1972 RECEIVED IJDV2 0 1972 tfGAL P-EEL 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. Lindsell (ICI, Director of European Monomer Group) was not satisfactory. Consequently,---. Dr. Harris was shown the equipment and given only the t st 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 rath r 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 pres nt a continuation of Dr. Viola's results at a meeting in 1974 which 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 ASI 00006820 CONFIDENTIAL 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 great st 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 wer sufficiently disconcerting to prompt immediate reconsideration of the U.S. Industry Program. Accordingly, the Talsk Force was to meet directly following our session. Among things to be reconsidered are metabolism studies and the epidemiology deleted from first program because of cost. Recipients of this memorandum are reminded that by agreement w'ith 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. WAK:md cc: Mr. W. S. Ferguson ASI 00006821 Vinyl Chloride Monomer - European Prelect Protocol Animal species: Sprague-Dawley 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. 65-95 animals per group. Time of exposure: 4 hours real time/day, 5 days per week for one year. Animals are observed until natural death. Professor Maltoni 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 of orft 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 of 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 of the work. Three Ph, D's work on this phase^of the work. A standard balanced laboratory*i"s supplied by a feed company according to his for--- mula. * 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 Maltoni' personally reads all slides. Color photos are made of tirnors. European Project Sponsors: Imperial Chemical Industries Solvay ctCie LTtri Montedison Rhone-Progil Research Investigator in charge Professor Cesare Maltoni Instituto Di Ancologia Bologna, Italy ASI 00006822 Vinyl Chloride Monomer Inhalation Study Cone.(ppm) No. at start/ surv. G* K* L* Vinyl acetate Vinyl chloride 2,500 10,000 6,000 2,500 * 95/22 70/30 70/45 * 7/3+lm 3/1+lm 0 * 2 4 500 250 70/50 70/50 1+lm? 1 - 50 70/50 0 _ 0 70/50 0 'f 8 (totay, do remember distrib. Exposure 4 hrs/day, 5 days/wk for one year; animals now 72 wks. old. Gross and microscopic autopsy made as animals die. G* - ceruminosa gland in ear K* - kidney L* - liver ASI 00006823 1