Document ZJxEVzK2nVpZ1r6jXoXqKywNY

JAN-02-1900 11 = 28 CHEMICAL MANUFACTURERS ASSOCIATION P.001/003 TO: FROM: RE: Vinyl Chloride Panel Health Committee Fax October 20, 1994 James Barter Ed Beeler Son Gilbert Mark Gruenwald James Knaak Patrick Logue Dave Penney avid Pun Jonathan Ramlow *v-Has Shah PPG GEON Westlake Borden OxyChem Georgia Gulf Vista Formosa Dow 412/434-2137 216/447-6459 713/963-1540 614/431-6611 716/286-3141 504/687-0294 512/331-2387 201/716-7283 517/636-1875 Conference Call Reminder A letter from James Swenberg regarding the Committee's visit to EPA is enclosed for your review prior to our conference call on Monday, October 24, at 9:30 a.m. If you have any questions, please call me at (202) 887-1192. Thanks. PAGES: SENDER: PHONE: 3 (including cover) Kim Seed (202) 887-1191 SL 107728 2501 M Street, NW, Washington, DC 20037 Telephone 202-087-1100 Fa* 202-887-1237 LS^RnmUiCn' j f aftSkOoiwiHiwnt JAN-02-1900 11:23 P.002/003 The Sthaet Of Haaltfc Ot0RflMftC Of EnvironDMlKal ScMScet tAd bfiattimi THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL KILL TM Vononky at HaaO Cirelim m Qwpd Hill 01 taco. ItomaM H0 Ok*{* MU. N- October 19,1994 Dr. Hasmukh C. Shah Manager, Vinyl Chloride Panel Qiemical Manufacturers Association 2501 M Street, NW Washington, D.C. 20037 Dear Dr. Shah: I enjoyed seeing you at the CUT Open House last week. This letter is a follow up to our conversation regarding the discussions that the Vinyl Otloride Panel held following our visit to the EPA. I would be interested in working with you on some of the issues that are still of concern such as decenremng the Tw of the etbenoguanine DNA adduct (EG), and quantitating the amount of the methyl purine DNA glycosylise (MPG) and P450 2E1 in tissues ofhuimns of different ages. We discussed the approach that I would use to determine the Tly, of EG. This would require the synthesis of (13Cj3-vinyl chloride. I would then expose groups of 3-4 rats using the closed chanter technique to the stable isotope and sacrifice them at different times (0,4,12, and 24 hours) after a 6 hour exposure to -1000 ppm VC. This would be repeated several times to determine the average Tw of EG using our GC/ high resolution MS methodology. Dr. Johannes Filser will visit me next week and I plan on discussing the details of the animal exposure with him, as he is an expert in the closed chamber technique. We are just setting up a quantitative polymerase chain reaction (PCR) method for measuring te obsession oftfceMFG DNA reparpeotem. We plan to evaluate age differences in rats and mice under our Superfund Basic Research Program proposal, providing it gets funded. What 1 hadn't considered until I met with the VC Prnel was doing this in human tissues of different ages. This may require slight adjustments in methodology and the synthesis of different printers. I believe that 1 can obtain human tissues from various tissue banks such as Vanderbilt University and the University of SL 10'7'729 P.003/003 Maryland. It may also be posable to get them from UNC and Duke. You indicated a desire to also examine P450 2EI expression in similar tissue. I would probably ask Dr. Fred Gucngerich to collaborate on this aspect He basal of the methods in place and could use the same tissue specimens that we use for MPG. These studies would be modest in size and scojie, but should provide very important information relevant to human risks associated with vinyl chloride exposure. The direct cost of this research would be ~ $50,000 per year for two years., with half of this for the DNA adduct studies, 35% fior the MPG detominations and 15% for the P450 2E1 studies. If this is handled as a grant to the university, there would be 44.5% overhead charged on the direct costs. If it is provided as a gift, there is no overhead. If a grant is desired, I win need to submit a research proposal and budget for university approval I hope this provides enough information for your next year's budget meeting. We can obviously increase or decrease the effort if this is deemed to litde or to great Please let me know what the Panel decides. Thank you again feu your interest in our research. Sincerely. James A. Swenberg, D.V.M.. PJtD. Director, Curriculum in Toxicology Professor, Environmental Sciences and Engineering, and Pathology si. I01730 TOTAL P.003 JAN-13-1900 17=20 Carlo H. Tamburro, lf.D.t M.P.H. Chief, Division of Occupational Toxicology Director, Liver Research Center School of Medicine. 119A University of Louisville Louisville. Kentucky 40292 FAX: (502) 582-8927 P.002/007 INIVERSITYqf IOUEMLLE October 27, 1994 Hasmukh Shaw, M.D. Chemical Manufacturers Association 2501 M. Street, N.W. Washington, D.C. 20037 RE: Study of Brain Cancer in Vinyl Chloride Exposed Workers Dear Dr. Shaw: As per Mr. Michael Sweeney's request, I am submitting our time and cost estimate for the rapid completion of our study or brain cancer occurrence m vinyl chloride exposed workers. Enclosed you will End a summary of the budgetary assistance needed for us to complete the updating and publication of this brain cancer and vinyl chloride exposure study. The need to update is due in part to the recent reorganization of the B.F. Goodrich Company. Although all the original workers are still physically present in the original B.F. Goodrich Company Bells Lane plant, that site is now split into three different corporate structures: B.F. Goodrich, Geon, and Zeon Kentucky. As I indicated to Mr. Sweeney during their recent visit, we are now reestablishing a working network with all three companies that will provide for scientific information to be made available. This updating, based on part-time effort, was expected to proceed to completion over the next two years and one-half years. We are prepared to proceed at a more rapid rate to complete the brain study with a 20-year prospective follow-up. This update would also provide a 25-year combined retrospective evaluation of the relationship of vinyl chloride to brain cancer. Each brain cancer case will be paired with all available matched controls and be analyzed by rank ordered analysis (reference Greenburg and Tamburro, JOM 1981). By this approach, each case will become an individual causal study. Each additional case will add further confirmation to the absence or presence of an identifiable relationship between any of 22 or more chemicals studied. In this manner we expect to revalidate our Erst observation, that no causal relationship exists between vinyl chloride exposure and brain cancer. The assistance we require, in the form of a grant to the University, would allow us to analyze workers exposed to vinyl chloride both by rank order and environmental levels. The study hypotheses to be confirmed are based on our initial observation. That* 1. Vinyl chloride exposure is not associated, clinically or histologically with brain cancer development, based on 20-years of prospective and 25-years of retrospective study. 2. There is an environmental vinyl chloride level or biological threshold (minimum environmental level) at which no association with any brain disease has been found. 3. The biological threshold for disease development for humans exposed to vinyl chloride is 50ppm (parts per million) or less TWA (time weighted average) exposure for less than 3 years. Livar nasaareli Camar and Laooiatory Department uf Madicina 1502) M8-S251 Diviiidn Of Occupational I oncology Dupartmaru of Pharmacology and Toxicology |50?) 588-15181 SL 107731 jhN-13-19@0 17=21 P.003/007 Dr. Shaw October 27, 1994 Page 2 We feel, scientifically, that the complete updated analysis will reconfirm these initial observations. Our time estimate regarding updating, verifying, analyzing, and preparing the report for submission to a recognized national peer reviewed journal would be completion in 7-9 months. Enclosed is a summary of the work and services required to update the B.F. Goodrich study database in this time frame. If I can provide any further clarification or information, please do not hesitate to give me a call. I look forward to hearing your response at your earliest convenience. Sincerely, CHT:sam Enclosures Carlo H. Tambunro, M.D., M.P.H. Professor of Medicine Director of Liver Research Center & Lab Professor of Pharmacology & Toxicology Chief, Division of Occupational Toxicology SL 107732 P.004/007 BUDGET FOR CMA PERSONNEL NAME TIME ON ROLE ON PROJECT SUMMARY COST Carlo H. Tambuno, MD, MPH H. Philip Fortwengler, MS Lark Reynolds, BS Mary Heck, MT Stephen W. Looney, PhD 10% 75% 75% 25% 20% Principle Investigator 13,000, Occupational Data Manager 33,066. Data Coordinator 15,190. Histological Procurement 7,420. Biostatistician 18,130. SUBTOTAL 86,806. EMPLOYEE CONSULTATIVE COSTS1 SUPPLIES, EQUIPMENT2 TRAVEL3 SUBTOTAL TOTAL (DIRECT COSTS) INDIRECT COSTS (25% S&W) GRAND TOTAL 2,140. 1,900. 200. 4,240. 91,046. 21,702. 112,748 1. Consultative cot for put and pretest key employee seeded to work with U of L tuff is work and environmental record dais collection and verification, also com for external independent biosutiideal and epidemiology review, 2. Include! ipecial computer updated software to increaae speed and efficiency of large data set analysis, use of university main frame (computer tune), telephone, mailing and luppon service* cost. 3. Costs that will be encountered to check ail regional hospitals for tissue verification of tumor diagnosis, especially the 100 not having complete cause of death dam. SI IO7733 JAN-13-1900 17:21 P.005/007 PROPOSAL AND OUTLINE LABOR AND SUPPLIES NEEDED FOR RAPID UPDATING OF THE 20 YEAR PROSPECTTVE/45 YEAR RETROSPECTIVE BRAIN CANCER STUDY ON VINYL CHLORIDE EXPOSURE INFORMATION NEEDED: 1. Contiguous Work Histories. Updating of the contiguous industrial work histories will need to be completed and verified on all employees from the original B.F. Goodrich Company and the two offspring companies, Zeon and Geon. Some employees have been continually employed, others are new hires, retired, or have died since the last update. A reasonable estimate is 600-700 employees per year from 1979-1993 need updating or verification. 2. Job Title Listings by Industry, Plant, Building, and Year. Review and updating of all past (before 1980) and new job titles (after 1980). New plant construction, renovations, and manufacturing location changes, which have occurred in recent years necessitate this step. In addition, there have been physical plant areas segregated into offspring companies. These job title listings will be used to produce a table of updated exposure ranking for all employees for all of the 1980's and 1990's. 3. Exposure Rankings. Exposure ranking updates are required on the cohort as described above. Updated ratings (ranking) will be given to all new job titles and old job titles used in the old and new sections of the plant(s) from 1979-1994. Participation of experienced employees will be needed and used for rating processes. 4. Chemical History. Updated documentation/verification of the continuous use of the 22 chemicals originally identified is needed. The area and personal monitoring data, where available, for these chemicals under evaluation will also be updated. This will be used for quantitative confirmation of rank order. The years and the buildings in which any of the 22 chemicals under study were used will also be reconfirmed. 5. Death Confirmation Data. Death certificate data is available on 484 vinyl monomer workers. Forty-six have incomplete data or need updating for cause of deaths. Retired, and separated employees data needs to be completed and reverified.6 6. Cancer Records. The histology, where and when ever available, will be examined for all brain cancer cases. This will be done for verification and confirmation of the histological tissue type. There will also be a follow-up conducted by phone or mail for retired former employees living outside the greater Louisville area if contact information is available. LABOR BXPB1 5 REQUIRED: Where needed, employees from B.F. Goodrich, Zeon, and Geon, paid by and working for the U of L staff, will be used to assist in gathering all pertinent work records and documents. The U of L staff will supervise the acquisition of all employee work records and the transfer of data via computer into the occupational interrelational data bank. SL 107734 JAN-13-19^0 17=22 P.006/007 RECORDS GENERATED: 1. Employee-Year Records. An estimated 600-700 employees per year for 15 years yields approximately 9,750 employee-years of work histories. 2. Maximum Estimated Cancer Cases. Brain cancer cases (all types) from 1945-1993 is estimated (based on all Kentucky cancer deaths 200/100,000) at no greater than 57/1,000. This estimate includes non-death cancer cases. At this point, we have identified 136 cancer cases (all types) and 10 brain cancer cases in the 484 deaths. 3. Analysis. Analysis regarding exposure and cancer by site and tissue type will be analyzed by nonparametic statistics. These methods are used and validated in the publication: Greenburg RA, Tamburro CH, Exposure indices for epidemiological surveillance of carcinogenic agents in an industrial chemical environment. Journal of Occupational Medicine 1981; 23(5):353-358. si 10 773s JAN-13-1900 17:22 P.007/007 SL 107736 Exposure Indices for Epidemiological Surveillance of Carcinogenic Agents in an Industrial Chemical Environment Richard A. Greenberg, Ph.0., M.P.H., and Carle H. Tamburro, M.O. A prospective system for establishing chemical expo The system for establishing exposure indices on an on sure indices was developed and implemented for 22 going basis was developed through employee work histo chemicals used at a Louisville chemical plant Validation ries and rank ordered job exposure categories. All jobs are of the indices was done statistically using industry-related classified uniquely by both area location and work de cancer (liver angiosarcoma) and worker-matched controls. scription by means of area-description (A-D) codes which A rank ordered system for exposures was used to identify a identify employment occurring in a particular building or relationship between the occurrence of disease and the area, independent of job; in a particular job. independent presence of a suspect chemical used in the industrial en of building or area; or by both area and description. vironment The exposure index combines two components, i.,, work history and job exposure category, by utilizing the A-D code. The chemical exposure rating is an ordered, A major difficulty in the epidemiology of occupy six-category ranking assigned to each A-D number for each calendar year, as follows: tonal carcinogenesis is obtaining accurate exposure data, especially if the data must be procured after cancer develops. While epidemiological investigations of out breaks of disease, infectious or chronic, are always retro spective, the long latent period between exposure to a causative factor and the occurrence of cancer compli cates this problem. Routine continuous recording of expo sure to possible carcinogens is an ideal goal. Unfortunate ly, this is not practical for most chemicals in a modem in dustrial setting. What is eminently practical, however, is a system utilizing rank ordering of exposures for highly suspect chemicals. The 6. F. Goodrich Louisville Chemical plant devel oped such a system in 1974 in response to the discovery of cases of hepatic angiosarcoma.15 This system was the basis of the initial reports. It was extensively modified during a prospective medical screening program estab lished by the University of Louisville under contract NOlCN-55212 with the cancer control program of the Nation al Caneer Institute.* * The author* art unaware of other similar existing data sets. Occupational studies are usual ly based on group, rather than individual, exposures. An excellent review of the literature is given by Gamble et al,* A recent discussion of a computerized system is given by Kerr.* Rating 0 1 2 3 4 S 6 Level of Exposure Absent from Environment (on leave, furlough, layoff, etc.) Lowest Exposure (includes exposure up to somewhere near one hour per day) Minimal Exposure to Low Levels (chemical in building -- not handled; low vapor pressure and dust level; individual prob ably works on different floor) Moderate Exposure (works around the chemical, but exposure is minimal; individ ual is frequently exposed to little spills or leaks and infrequently -- less than once per month -- to large spills or I aks) Works in Area Subject to High Occupation al Exposures (normally exposure is mini mal, but large spills or leaks occur once per month or more) Works in Areas Where Level is High (expo sure levels in erea are frequently high; might consider that some risk is involved if the chemical is very toxic) Intimate Contact -- Skin or High Inhala tion (includes individuals with daily and direct contact with the chemicals, such as Stem dw LMwnity erf UuiivMI*. Dept al Community htulth (Dr. Ciatabarp and Dopt aI Mod(tin* (Dr. Tombunol P.O. Boo 15260. Loumnllo. KY 40252. poly cleaner in the old days and those who handled slurry) RlffMN nM eMNIW fll M*y. INI. Vi e,Mi 353 TOTAL P.007 r FtLtNG INSTRUCT!0NS: | \liu^(bb-ate l&M&i SL 107738