Document MOwEvjEE6aeBLyXyNnaNy8Ez

BORDEN SERVICES COMPANY "QUALITY BUSINESS SOLUTIONS" MARK A. GRUENWALD, C.I.IL Associate Director Product Safety/Technical Services June 4, 1996 Hasmukh Shah, Ph.D. Manager, Vinyl Chloride Panel Chemical Manufacturers Association 1300 Wilson Blvd. Arlington, VA 22209 Dear Has: ILSI's RSI group has initiated a project to use genotoxicity data in cancer risk assessment. Vinyl Chloride will be one of the case studies. (See attached) Our Vinyl Chloride Health Committee may want to discuss this, if they haven't already, in the most recent conference call which I missed. Associate Director >/,-9U-Or Attachment Phone: (614) 225-3459 Fax: (614) 225-7638 180 East Broad Street Columbus, OH 43215-3799 CMA 118955 i from page 1> RSI Update on essential elements, dose selection in chronic rodent hioassays. microbial risk assessment, human variability, and other issues is completed and disseminated. hi tins issue of RSI Update u c highlight two ness RSI projects on genotoxiafs and reproducttvc/develnpmeinal to stars. These projects, like mam others at RSI. should provide benefits to individuals and organisations seeking unproved, balanced, and reliable scientific input on issues of public interest and concern. UV would like to hear from sou whenever xou draw on iiu icsults of RSI projects, loi whatever reason. Ik'hen our work is of value to van. sour < edback in turn u ill be ot smear value to us. --- Jeff'erv A. Fomn, Ph. D. New Projects Use of Genotoxicity Data in Cancer Risk Assessment Historically, genotoxicity data have been used as pu't o: hazard identification u e . to classify carcino gen- a- genutouc or nongenotoxic i. but not ns part of :r,e do-c-re-non-c ,^^'sment to quuntitativ ely estimate -an^et risk The current scientific and regulators cli mate is such that the use ol endpoints other than tu mors to quantitatively estimate cancer risk is on the Munzon Thm RSI project was initiated to address the question or w hether and host genotoxicity data should a us.jd tis part o! a cancer risk assessment. \ -mail v. i irking group ot distinguished scientists _.m'.. :ied nv RS! agreed that the qualitative and quan- u-e of cnapoints othei than tumors iDVA. ad- G lJ t '! Iiiui.lt /*. .Cll J..5. L ' i ' C i lU K'i t UttLu. ii'f * ills' J.PnJ I*i - i'. gmxitoxicuv data mcluding mutagenicity. among .'tucr- in a cancer risk assessment is an is-ue worths id' in' c-:,cation The working gnoup suggested that the goal o! il >' project--to determine now to use genotoxmit> anti other information in a cancer risk assess ment--shouid be pursued initial!) through the use ot case studies These case studies w ill ins oh e the developmem of cancer risk estimates ktjgj^nii'-^qhM^nces: ailatoxm. benzene, butadiene, avrdv in vl chloridejSach .use studs will include the loIltWmg, a cancer risk, estimate derised following the 1986 L ,S. EPA cancer risk assessment guidelines. a cancer risk estimate derived following the pro posed res ised ITS EPA cancer risk assessment guidelines using the LED for tumor response i dose causing a 1 Off tumor response! as the "point of departure" (i.e.. the starting point from w hich to extrapolate to the low dose-response region j. and a cancer estimate derived by choosing a point of departure from endpoints other than tumors i i.e.. DNA adduct formation, in \ is o mutation data, etc that are mechanistically linked to the observed tu mor response Expert scientists identified by the working giour w ill be asked to generate first drafts of the case studies by September 1996 L'pon completion or the draft'-, authors, reviewers, and the working group will meet i likely in late 1996; to review the case studies and to discuss their implications for quantitative cancer risk assessment. The product of this project is anticipated : be : reiv'-t published in the neer-m11 ieu ed literatum or as a stand-alone monograph on the quantitative ap plication of genotoxicity data in cancer risk assessment Contact: Dr Clint' Scarano at RSI. Methods for Assessing Sperm Parameters Regulatory agencies are in the process of rev ising test guidelines for reproductive toxicity studies, and are proposing the addition of assessments of sperm pa rameters including motility, morphology, and counts. While these assessments can provide valuable infor mation for the determination of potential reproductive toxicity, the methods for conducting the assessmenthave not been well developed. In addition, there is dis agreement about the optimal collection site for obtain- CMA 118956