Document Dv6rVRNyrYb48Bkn6zymnOYn4

JAN-02-1900 11:40 P.002/003 The School of Public Hcolifc Department of Bwlronmnui Scmocoi oo4 fintweaiac THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL The Unhcuky of North Ctrota* t Oxpel Hill CBf 7400. DMtwi HH Chtpt) Hill, ftC. 27J9M40Q October 19,1994 Dr. Hasmukh C. Shah Manager, Vinyl Chloride Panel Chemical Manufacturers Association 2501M 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 the synthesis of [1JCJ-vinyl chloride. I would then expose groups of 3-4 rats using the closed chamber 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 rimes to determine the average T1/a 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 the expression ofthe MPGDNA repair protein. We plan to evaluate age differences in rats and mice under our Superfund Basic Research Program proposal, providing it gets funded. What I hadn't considered until I met with the VC Panel was doing this in human tissues of different ages. This may require slight adjustments in methodology and the synthesis of different primers. Ibeliev that I can obtain human tissues from various tissue banks such as Vanderbilt University and the University of R&S 144664 JfiN-02-1900 11=40 P.003/003 Maryland it imy also be possible to get them from UNC and Duke. You indicated a desire to also examine P450 2E1 expression in similar tissue. I would probably ask Dr. Fred Guengerich to collaborate on tins aspect He has all of the methods in place and could use the same tissue specimens that we use for MPG. ( These studies would be modest in sire and scope, but should provide very important information relevant tp 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% for tte MPG determmations and 15% for the P450 2E1 studies. If this is handled as a grant to the movezsity, there would be 44.5% overhead charged on the direct costs. If it is provided as a gift, there is no overhead. If a gram is desired, I will need to submit a research proposal and budget far university approval. I hope this provides enough information for your next year's budget meeting. We can obviously increase or decrease the effort if dtis is deemed to little or to great. Please let me know what the Panel decides. Thank you again for your interest in our research. Sincerely, James A. Swenberg, D.V.M., Ph.DDixector, Curriculum in Toxicology Professor, Environmental Sciences and Engineering, and Pathology R&S 144665 TbtflL P.003