Document 4O5rYpgKoDEmJkRYpzG0wdZQ

BORDEN SERVICES COMPANY "QUALITY BUSINESS SOLUTIONS" MARK A. GRUENWALD, CXH. 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 ofthe 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 /cac Attachment Phone: (614) 225-3459 Fax: (614) 225-7639 180 East Broad Street Columbus, OH 43215-3799 BFG 00061 (from page RSf Lpclan on essential elements, dose selection in chronic rodent bioassays, microbial risk assessment, human variability, and other issues is completed and disseminated. In this issue qf RSI Update vt c highlight mo new RSI projects on genotoxiarx and rcprodiu nve/dcvclopmental toxicity. These projects, like main others at RSI. should provide benefits to individuals and organizations seeking improved, balanced, and reliable scientific input on issues ofpublic interest and concern. We would like to hearfrom you whenever uni draw or. the results of RSI projects, for whatever reason. When our work is of value to vou. rowfeedback in turn will be of great value to us. Jeffeiy A. Foran. Ph. D New Projects Use of Genotoxicity Data in Cancer Risk Assessment Historical!). genotoxicity data have been used as part ot hazard identification u.e.. to classify carcinosens a* genotoxic or nongenotoxic i. but not as part of he dose-re-wnse assessment to quantitative!) estimate ancer n:sk. The current scientific and regulators di late is such that the use of endpoints other than tu- or> to quantitative!) estimate cancer risk is on the rizon. Thi^ RSI project vs'as initiated to address the estion of whether and how genotoxicity data should t^cc a' pari of a cancer risk assessment. \ >mali s\ orking group of distinguished scientists * ened b\ RSI agreed that the qualitative and quan- unc of endpoints other than tumors iDNA adloriiiaiiun. -.el! proliferation data, m vitro and in genotoxicit) data including mutagenicity, among ,. in a cancer risk UNsessment is an issue worth) wiiguiion. The w orking group suggested that the this project--to determine how to use genotoxnd other information in a cancer risk assessshouid be pursued initial!) through the use of dies. These case studies w ill involve the develol cancer risk estimates f^Jl<:iur?ubstances: benzene, butadiene, atf&vinyl chloride^Bach . will include the following. :er risk estimate derived foliowing the 1986 :PA cancer risk assessment guidelines. iy risk estimate derived following the proevised t'.S. EPA cancer risk assessment guidelines using the LED[(i tor tumor response tdose causing a lOG tumor response i as the '`point of departure" (i.e.. the starting point from which to extrapolate to the low dose-response region 1. and a cancer estimate derived by choosing a point of departure from endpoints other than tumors the.. DNA adduct formation, in vivo mutation data, etc > that are mechanistically linked to the obser\ ed tu mor response. Expert scientists identified by the working group will be asked to generate first drafts of the case studies by September 1996. Upon completion of the drafts, authors, reviewers, and the working group will meet ilikeh in late 19^6) io review the case studies and to discuss their implications for quantitative cancer risk assessment. The product of this project is anticipated tv be a repon published in the peer-reviewed literature or as a stand-alone monograph on the quantitative ap plication of genotoxicit) data in cancer risk assessment Contact: Dr. Gino Scarano at RSI. Methods for Assessing Sperm Parameters Regulator) agencies are in the process of re\ i*ing test guidelines for reproductive toxicit) studies, and are proposing the addition of assessments of sperm pa rameters including motility, morphology, and count*. While these assessments can provide valuable infor mation for the determination of potential reproductive toxicit). the methods for conducting the assessments have not been well developed. In addition, there is dis agreement about the optimal collection site for obtain- BFG 00062