Document x5pzbbzk5L14B1ONaBVboE326

07/2.1,96 09:35 0202 559 3917 ILSI 2RD FLOOR <2)001 Risk Science Institute International Life Sciences Institute Robert Venezia Chemical Manufacturers Association 1300 Wilson Blvd. Arlington, VA 22209 VTA FACSIMILE July 15, 1996 Dear Mr. Venezia; It was a pleasure speaking with you this morning- Per our conversation, attached arc a fact sheet and a list of working group members for our project on the Use of Non-Tumor Data in Cancer Risk Assessment. I am happy to hear that the CMA Vinyl Chloride Health Committee has expressed an interest in this activity. Please share this information with the Committee. Genotoxicity data have been used historically as port of hazard identification (i.e., to classify carcinogens as genotoxic or nongenotoxic) but not as pan 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 data should he used as part of a cancer risk assessment. A component ofthe project includes the development of cancer risk assessments for four chemicals using genotoxicity and other data, and following the draft revisions to the U.S. EPA cancer risk assessment guidelines. Partial funding for the project has been provided by the American Petroleum Institute (APT) and the U.S. EPA. We are seeking further funding from a variety of sources from both the private and public sectors. At your request, I would be pleased to submit a full proposal to the CMA Vinyl Chloride Health Committee. Please call me at 202-659-3306 if you have any questions. Gino Scarano, Ph.D. Senior Scientist cc; Dr. Jeffery Foran, Executive Director, RSI 1126 Sixteenth St, N.W., Washington, D.C. 20036-4804 Phone: (202) 659-3306 Fax: (202) 656-3617 E-mail; rei@dc.ilsi.org CMA 118952 07/24/96 09:58 0202 659 3617 ILSI 2RD FLOOR <2)002 Risk Science Institute International Life Sciences Institute FACT SHEET Using Non-Tumor Data in Cancer Risk Assessment The current scientific and regulatory climate is such that the use of data on additional endpoints to supplement and refine cancer risks obtained using tumor incidence 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 small working group of distinguished scientists was convened by the ILSI Risk Science Institute (RSI). The working group agreed that the qualitative and quantitative inclusion of endpoints other than tumors in a cancer risk assessment is an issue worthy of investigation. Examples of non-tumor endpoints that might be utilized include genotoxicity data (mutagenicity, DNA adduct formation, etc), cell proliferation data, and cell death data. The working group suggested that the goal of this project - to determine how to use genotoxicity and other ancillary data along with tumor data in a cancer risk assessment - should be pursued initially through the use of case studies. These case studies will likely involve the development of cancer dose-response relationships for four substances: afiatoxin, benzene, butadiene, and vinyl chloride. Each case study may include the following: 1. A cancer potency estimate derived following the existing U.S. EPA cancer risk assessment guidelines. 2. An estimate derived following the proposed revisions to the U.S. EPA cancer risk assessment guidelines using the LED10 for tumor response (lower limit on the dose causing a 10% tumor response) as the "point of departure" (i.e., the starting point from which to extrapolate to the low dose-response region). 3. An estimate derived by choosing a point of departure from endpoints other than tumors (i.c,, DNA adduct formation, in vivo mutation data, cell proliferation data, etc.). The endpoint must be mechanistically linked to the observed tumor response. 4. An estimate derived by using biologically-based dose response modeling, ifadequate data are available. Individuals will be identified who will be asked to generate first drafts ofthe case studies by the fall of 1996. Upon completion of the drafts, authors, reviewers and the working group will meet (likely in late 1996/early 1997) to review the case studies and to discuss their implications for quantitative cancer risk assessment. The product of this project is anticipated to be a report published in the peer-reviewed literature or a stand-alone monograph on the quantitative application of genotoxicity data in cancer risk assessment. RSI staff will manage the project and coordinate preparation of the final report. For more information on this project, please call Dr. Gino Scarano (202-659-3306), July 1996 1126 Sixteenth St, N.W., Washington, D.C. 20036-4804 * Phone: (202) 659-3306 Fax: (202) 659-3617 E-mail: rei@dc.ilsi.org CMA 118953 07/24 98 09:37 0202 839 3817 ILSI 2RD FLOOR GENOTOXICITY MEETING Participant List Richard J. Albertini, Ph.D. University of Vermont Vermont Cancer Center I South Prospect St Burlington, VT 05401 P: (802) 656-8347 F: (802) 656-8333 Harvey Cleweil ICF Kaiser 603 E. Georgia Street Ruston, LA 71270-3935 P: <318) 255-1800 F: (318) 255-4960 Vickie Dellarco, Ph.D. U.S. Environmental Protection Agency 401 M Street, SW (8601) Washington, DC 20460 P: (202) 260-7336 F: (202) 2600393 Sheila Galloway, Ph.D. Merck Research Lab, W-45-304 Sumney Town Pike West Point, PA 19486 P: (215) $52-7292 F: (215) 652-7758 David Jacobson-Kram, Ph.D. Microbiological Associates, Inc, 9900 Blackwell Road Rockville, MD 20850 P: (301) 738-1000 xl341 F: (301) 738-1063 Mary Paxton, Ph.D. American Petroleum Institute 1220 L Street, NW Washington, DC 2Q005 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 Sc Gamble Company Miami Valley Laboratories P.0. Box 398707 Cincinnati, OH 45239-8707 P: (513) 627-0674 F: (513) 627-1908 Gino Sorano, 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. N1EHS Mail Drop A2-03 P.O. Box 12233 Research Triangle Park. NC 27709 P: (919) 541-3455 F: (919) 541-4634 sheIbyniehs.nih.gov James A. Swenberg, Ph.D. Professor University of North Carolina Campus Box 7400, Rosenau Hall Chapel Hill, NC 27599-7400 P: (919) 966-6142 F: (919) 966-6123 Curtis Travis, Fh.D. Canter for Risk Management 1060 Commerce Park Drive Oak Ridge, TN 37830 P: (423) 576-2109 F: (423) 574-9887 @003 UMA V189b4