Document 0qZeXNrMOeVKL6raDyg2OyOwb

( SM 32 l#v. 9 57' n SHELL OIL COMPAK to MESSRS. W. G. EDDLEMANO R. H. FINDLEY< This Copy For E. JOYNER, A. J. MARTIN R. L. MAYCOCK<> R. F. NELSON-O3 R. J. REYNOLDS C= H. E. WALKERS date APRIL 16, 1974 FROM MANAGER, INDUSTRIAL HYGIENE HEAD OFFICE subject VCM MEETING - APRIL 15, 19 74 The meeting was held at the Industrial Bio-Test offices in Northbrook (Chicago), Illinois. Attendees are noted on Attachment 1. Dr. Goode, who is in charge of the inhalation work at the Decatur Lab reported on mortality results to date. These are shown as Attachment 2. He emphasized that the pathology was only in the mice. Grossly, the effects are manifested as subcutaneous masses, probable liver tumors and tan Eoci on the lungs. The first observed change in the animals is a swelling of the abdomen. Death may occur suddenly within 48 hours with no other apparent symptoms. Goode ascribes this to internal hemorrhage. To date there have been no gross observable effects on the control animals. Dr. Gordon, the Bio-Test pathologist, then gave his impressions. He called attention to a higher incidence of tumors in the female mice. The compound-induced lung adenomas are indistinguishable from the spontaneous adenomas seen in these animals, but the incidence appeared to be dose-related. Although some strains of mice do show spontaneous hemangicsarcomas of the liver, Gordon has seen this occur spontaneously only once at IBT. Dr. Gordon, and Dr. Kociba who looked at the slides, agreed that the liver lesions are the same as seen and reported by Dr. Maltoni. Gordon's data are presented in detail in Attachment 3. Note that there are some discrepancies with the gross data reported by Goode. This, however, was explained as a sex-identification error in the mice on a gross basis. Microscopic visualization of the gonads was used to verify Gordon's data. I asked about the discrepancies between the five-month and seven-month data. For example, six female mice at 2,500 ppm should have died of tumors in that period. Gordon's data show 15 females dying within that period. The IBT people were unable to explain the differences, but were going to check into it. The consensus of the group was that despite these minor discrepancies, the tumors were real and they confirmed Maltoni's findings. On a ppra-hour basis, the tumors appeared at 1/40 the level that were noted in Maltoni's rats. This may be species- or strain-specific. Zwicker (BFG) and Kennedy (Conoco) both stated that there was a report circulating in Europe that Maltoni is seeing, M ... avalanches of hemangicsarcomas in his mice." No data were available, but the feeling was that these new Maltoni results were similar to those at IBT. SCC 5-0671 2 The government people present would make no commitment about new levels. During lunch, however, I asked Lassiter what he thought the action might be. He felt that OSHA would have to review their position and could either now promulgate a proposed permanent standard sooner or could revise the emergency standard. He felt that the results reported would support the NIOSH recommendation of 1 ppm. Fairchild later agreed that any so-called "zero standard" would be based on feasible analytic techniques available. He stated that although NIOSH could analyze to levels under 1 ppm, the methods were not feasible for most installations. The discussion then turned to the nature of follow-up research. Dr. Stara stated that he already has orders from EPA to start inhalation toxicity studies on VCM. His own attitude is that there should be no duplication of MCA work, but rather, there should be a coordinated governmentindustry approach. Fairchild also stated that NIOSH will not be'doing any animal work - it preferred to see what MCA will be doing before taking any action. He also stated that there is an HEW committee to coordinate toxicology and related programs which is active. A subcommittee has been formed to recommend protocols for testing carcinogens. The recommendations of the subcommittee are to include methods of determining levels of exposure which would lead to socially acceptable risks from carcinogens. (Emphasis mine). The Federal representatives thought that they would prefer to wait until the report was out before embarking on animal studies. Expected date of publication is before the end of May. With this the research coordinators recommended two action items. First was to cease mouse exposure at nine months. This will be equal to half a mouse's lifetime and would be comparable to a one-year exposure for rates and hamsters. Secord, the coordinators recommended that MCA investigate the costs of doing animal studies on larger numbers of animals at lower levels. The exact levels will be determined later, probably in conjunction with the HEW subcommittee report. An offhand estimate was that such studies would add about $200M-$500M to the overall budget. Stara pointed out that EPA and FDA might help fund low-level toxicity studies. He suggested writing to Dr. Charles Edwards (Assistant Secretary of HEW for Health) and to Russell Train (EPA Administrator) for assistance in obtaining the cooperation of the National Toxicity Research Center (Pine Bluff, Arkansas) in kilo- and mega-mouse studies. There was one other area of importance at the meeting. Jane Brodie of the New York Times phoned Dt. Fairchild at Northbrook. She seemed to know about the meeting, who would be attending, the agenda, and the results. She wanted a statement from Fairchild regarding the significance of the results and what the Government would be doing about it. Fairchild said that he was at the meeting to listen, and was not sure he could get back to her in time for her deadline. By the time he left at 3:00 p.m. CDT, he had not called her back. MCA was preparing a statement for distribution on April 16. It was not completed at the meeting and would probably be done by Clark, Johnson, and SCC 5-067; 3 Blewitt on their flight back to Washington. It was agreed that the statement would be factual (rather than interpretive or speculative), would point out that the results were preliminary, and that the results had been made available to government (OSHA, NIOSH, and EPA) the same time as they were released to the industry sponsors. It was to be clear that any statements would come from MCA rather than from Bio-Test or from the individual company sponsors. Blewitt also mentioned that CBS was preparing a one-hour special on vinyl chloride. They were sending a camera to Goodyear at Niagara Falls along with Dr. Selikoff for the program. The meeting adjourned at 4:30 p.m. CDT. Attachments see 5-067 ATTENDEES Zeb G. Bell A. S. Cummin W. D- Harris M. N. Johnson F. Kennedy R. J. Kociba H. L. Kusnetz W. E. Rinehart M. Smith T. R. Torkelson R. N. Wheeler B. F. Zwicker R. F. Blewitt A. C Clark K. D. Johnson J. W. Goode D. E. Gordon M. L. Keplinger E. J. Fairchild D. V. Lassiter J. F. Stara PPG Industries Borden Company Uniroyal Inc. B. F. Goodrich Conoco Dow Shell Oil Company Ethyl Corporation Air Products Dow Union Carbide Corporation B. B. Goodrich MCA MCA MCA IBT IBT IBT NIOSH OSHA EPA Attachment 1 see 5-0674 Attachment: 2 SEVEN-MONTH MORTALITY DATA - AS OF APRIL 15, 1974 (Deaths from all causes) Species Rat Mouse Hamster Control M/F 4/4 (2/3^a) 16/5 (S/2) 13/22 (9/18) 50 ppm M/F 10/8 (5/1) 31/9 (26/6) 20/20 (16/6) 200 ppm M/F 6/9 (6/1) 7/13 (2/2) 22/29 (16/20) 2,500 ppm^) M/F 5/7 (3/4) 18/13 (8/7) 27/27 (15/15) NOTES: (a) Nos. in ( ) refer to corresponding five-month mortality data. (b) In addition, one group of 100 female rats had been exposed to 2,500 ppm, but with food available ad lib. There have been no deaths in this group to date. see 5-0675 Group T-I T-II T -III ^noJAOucil B I O. - T E S T J!a&ofcU&%uu^, 3nc. 1010 FRONTAGE road NORTH BROOK . 1 LLI NOI S 60062 ^ "C. O' j L v l r- Summary of Mortality fit Tumor Data Among Vinyl Chloride Mice IBT Number 663-03222 (MCA) No. Mortalities with Neoplasms 4 (1 Male, 3 Females ) 6 (1 Male, 5 Females) Location <:>i Tumors Lung Liver 2(50%) 2(50%) 3(50%) 4(66. 1%) " ------------ Skin l Metastasis--> Lu. \ 2(50%) \ 2 \ 2(33%) 1 19 (4 Males, 15 Females) 17(89. 5%! 17(89. 5$%' 3(15. 8%) _ l\ h> 1 L cu o Y LCv/- r \ ___ i j/ 1 4 <Xv\ \ ,-A \ . - 4^ -u r1 v u* 5- sec 6 76 9tul)ut,'tal B I O - T E s T JfaivyioJ&nci: 'he. IflIO FRON1 AGP'HOAD MORTHflPOOK.iiliMOIS 60 067 Summary of Tumors in Vinyl f'Moridc Exposed Mice IDT Number 6bJ-03222-MCA Group, Animal No. , Sex r-i 1023 Male 1110 Female 1119 Female 1200 Female Histopathologic Findings Date of Death. Lung Liver . AA (s)* HS (s)** AA (s), Metastatic Skin Tumor HS (3) Metastatic Skin Tumor Skin *** EC. (para-aural) 3-20-7 3-24-74 EC (< MC+ (Femoral region) 3-30-74 r - ii 13 "7 Female 1 309 Female 1889 Male 1382 Female 1 2 ^cma le 1297 Female r-in 1538 Fcmale 1 532 Female 15 62 Female 1598 Female 1405 Male 1 4n/l Male 1.. Female 153 1 F emale 1 588 Female 1593 Fcma le 150 5 Fcmnlc 1 565 Fc ma le 1409 Male 15 4 3 Female 1 5 44 F ema le 1546 Female 15?" iremale 14 2. Male ;477 Female Metastatic Skin Tumor HS (s) AA (s) HS HS (s) AA (s) HS (s) AA (s) AA (s) AA (s) AA (s) AA (s) AA (s) AA (s) AA (s) HS (s) HS (s) HS (s) HS (s) HS (s) IIS (s) HS (s) AA (s) AA (s) AA (s) AA (s) AA (s) AA (S) AA (s) HS (s) HS (s) HS (s) HS (s) HS (s) HS (s) IIS HS (s) AA (s) AA (s) HS (s) AA (s) HS (s) Metastatic Skin Tumor? EC(Abdomen) 3-5-74 3-18-74 3-25-74 4-2-74 4-5-74 EC & MC (Inguinal Region) 4-9-74 LS> 3-6-74 3-7-74 3-8-74 2-25-74 3-22-74 3-22-74 EC k MC (Femoral region) 3-23-74 3-25-74 3-30-74 4-; -74 4-3-74 4-5-74 4-5-74 4-5-74 MC (Axillary region) 4-5 - 74 4-7-74 4-8-74 EC (Para-Aural) MC ( Abdomen) EC( Pelvic region) 4-9-74 Kev to .Svmj-.oN - A 1 vcol n j* o n i c Adenoma nf Lv.ng (AAJ Hemn ng ios a rcomn of Liver ( HS) *** Epidermoid C;i rciimma of .Skin (EC) + Mammary Cnrcinmmi of Skin (MC) (2> ^yn`P! losarcoma of Thynms O' \\ r`< see 5-0677