Document YGMKZGGjy1ZyGMNqjELJL11Q8

07/26/90 10:31 202 859 3817 1LSI 2RD FLOOR 121001 Risk Science Institute______________________ ____ _____________ International Life Sciences Institute Robert A. Venezia, Dr.Ph. Panel Manager CHEMSTAR Department Chemical Manufacturers Association 1300 Wilson Blvd. Arlington, VA 22209 July 26,1996 VIA FACSIMILE RE: Request for Funding Support of Project on the Use of Non-Tumor Data in Cancer Risk Assessment Dear Dr. Venezia: II was a pleasure speaking with you this morning. Per your request, this letter presents a brief proposal requesting funding from the CMA Vinyl Chloride Panel Health Committee for our project on the use of non-tumor data in cancer risk assessment Genotoxicity data have been used historically as part of hazard identification (i.e., to classify carcinogens as genotoxic or nongenotoxic) but not as part of the dose-response assessment to quantitatively estimate cancer risk. The current scientific and regulatory climate is such that the use of endpoints other than tumors to quantitatively estimate cancer risk is on the horizon. This project was initiated to address the question of whether and how genotoxicity and other data should be used as part of a cancer risk assessment. A component of the project includes the development of cancer -- risk assessments for four chemicals using genotoxicity data and other data, and following the draft revisions to the U-S- EPA Cancer Risk Assessment Guidelines. The cost of the project is approximately $170,000. Partial funding for the project has been provided by the American Petroleum Institute (APT) and the U.S. EPA. We are also requesting funding support from a variety of sources from both the private and public sectors. Greater detail about the project is provided below. On 4 March 1996 a working group of distinguished scientists, (Attachment A) with expertise in genotoxicity and risk assessment met at the ILSI Risk Science Institute (RSI). The group agreed that the qualitative and quantitative use of endpoints other than tumors in a cancer risk assessment is an issue worthy of investigation. Examples of non-tumor endpoints that might be used include genotoxicity (mutagenicity, DNA adduct formation, etc.), cell proliferation, cell death, and others. The working group suggested that the best way to address the issue would be through case studies using the draft revisions to the U.S. EPA Cancer Risk Assessment Guidelines. Four chemicals were nominated for this exercise (aflatoxin, benzene, butadiene and vinyl chloride). 1126 Sixteenth Si., N.W., Washington, D.C. 20036-4804 Phone: (202) 659-3306 Pax: (202) 659-3617 E-mail: rsi@4c.ilsi.org CMA 118949 07/28/96 10:32 202 639 3817 ILSI 2RD FLOOR 121002 Each case study will include cancer risk estimates derived from: 1) the existing (1986) U.S. EPA Cancer Risk Assessment Guidelines; 2) the proposed revised U S. EPA guidelines using the LED10 (lower 95% confidence limit on the dose causing a 10% increase in tumor response) as the "point of departure", or the starting point fiom which to extrapolate down to the low dose-response region; 3) a point of departure from endpoints other than tumors (i.e., DNA adduct formation, cell proliferation, genotoxicity, etc.) that must be mechanistically linked to the observed tumor response; and 4) the use of biologically-based dose-response modeling, if adequate data are available. Following the development and review of the case studies, RSI plans to hold a workshop, likely in Washington, DC, during late 1996/early 1997, to provide an opportunity to disseminate and discuss the results of the case studies and the implications for inclusion of such data in a risk assessment. The results of the project would be published either in the peer-reviewed literature or in a monograph published by ILSI Press. As mentioned above, the total project cost is approximately $170,000. We are requesting funding support from the CMA Vinyl Chloride Panel Health Committee of $10,000. A rapid response to this request would be most helpful given the time line associated with the project. Should you have any questions or need any other information, don't hesitate to contact either of us at 202-659*3306. We extend our thanks for your consideration of this request, and look forward to your positive response. Sincerely, Gino Scarano, Ph.D. Senior Scientist Jeffery A. Foran, Ph.D. Executive Director CMA 118950 I 07/26/99 10:32 0202 659 3017 I LSI 2RD FLOOR % GENOTOMCITY MEETING Participant List 12)003 Richard J. Alberdni, Ph.D. Unlvcniiy of Vermont Vermont Cancer Center 1 South Prospect St. Burlington, VT 05401 P: (802) 656-8347 F: (802) 656-8333 Harvey Clewell ICF Kaiser 603 E. Georgia Street Ruston. LA 71270-3935 P: (318)255-4800 F: (3I8)255-960 Vickie Dellarco, Ph.D. U.S. Environmental Protection Agency 401 M Street, SW (8601) Washington. DC 20460 P: (202) 260-7336 F: (202) 260-0393 Sheila Galloway, Ph.D. Merck Research Lab, W-45-304 Sumney Town Pika West Point. PA 19486 P: (215) 632-7292 F: (215) 652-7758 David Jacobson-Kram, Ph.D. Microbiological Associates, Inc. 9900 Blackwell Road Rockville, MD 20850 P: (301)738-1000x1341 F: (301) 738-1063 Mary Paxton, Ph D American Petroleum Institute 1220 L Street, NW Washington. DC 20003 P: (202) 682-8000 F: (202) 682-8270 Julian Preston, Ph.D. CUT 6 Davis Drive, P.O. Box 12137 Research Triangle Park, NC 27709 P: (919) 558-1367 F: (919) 558-1300 Steven H. Robison, Ph.D. Corporate P&RS Division The Procter & Gamble Company Miami Valley Laboratories P.O. BOX 398707 Cincinnati, OH 45239-8707 P: (513)627-0674 F: (513) 627-1908 Gino Scarano, Ph.D. ILSI Risk Science Institute 1126 Sixteenth Street, NW Washington, DC 20036 P: (202) 659*3306 F: (202) 659-3617 Michael Shelby, Ph.D. NIEHS Mail Drop A2-03 P.O. Box 12233 Research Triangle Park, NC 27709 P: (919) 541-3455 F: (919) 541-4634 shelby4bnMii.iiih.gov James A. Swenberg, Ph.D, Professor University of North Carolina Campus Box 7400, Rnsenau Hail Chapel Hill, NC 27599-7400 P: (919) 966-6142 F: (919) 966-6123 Curtis Travis, Ph.D. Center for Risk Management 1060 Commerce Park Drive Oak Ridge, TN 37830 P: (423) 576-2109 F: (423) 574-9887 CMA118951