Document eGMGMKdY8676Bv6oZQq4mYjM

Benzene~ask Force (BTP) American Petroleum Xnstitute at The Airlie Foundation warrenton, VA Meeting Minutes - Subject to Approval Wednesday, Sept~er 23, 19~2 Attendees Pat Beatty Mike Bird Rudy Breglia Peter Craig Cosmo DiPerna Bob Drew Jennifer Galvin Chuck Lambert Davia-Mongillo Mary Paxton Gerry Raabe Louise Scott John Sepesi Michael W.ells Li Yang Lemone Yielding Affiliation Chevron Exxon BP Mobil Mobil API Phillips Uno c a l API API Mobil API Shell Amoco ARCO U. of Texas The Benzene Task Force (BTF) met from 1:00 to 3:30 following the workshop "Mechanisms -of Ben-zene Toxicity as a Basis for Risk Assessment" (agenda and list of attendees attached). TITe purpose was to determine how the BTF's research budget should be allocated in light of the information and opinions that had been exchanged in the previous day and a half. It was agreBd that there -was strong support for continuedfunding of Rich Irons' work at the University of Colorado on the specific targets among bone marrow cells for toxicity caused by benzene and its metabolites. Broadening of his work to include investigations involvin~ human bone marrow in vitro, whole animal exposure, and-human cancer chemotherapeutic agents was endorsed. It was agxeed that there are still gaps in our knowledge of ben-zene metabolism and kinetics. Lovelace/ITRI with Rogene Henderson as PI was deemed a more suitable institution to pursue this aspect of the research and cooperate with Irons in providing 1 October 21, 1992 BP-00011898 him with tissues from treated animals. A proposal concerning biomarkers of benzene exposure has also been submitted by this researcher, and its support would forward the more long-term goals of developing reliable indicators of exposure and early signs that could aid in monitoring biological response. CIIT will be notified of this change. The consensus was that the likelihood of identifying an animal model that could be used in illuminating the leukemogenic mechanism in humans was so remote that further allocation of funding to this objective would not be cost-effective for API. Although it was granted that endpoints indicative of genotoxic activity have been observed in association with benzene exposure, it was generally agreed that their interpretability with respect to the carcinogenic process of primary concern is so uncertain that pursuit of this line of research would not be anticipated to have much impact on risk assessment for benzene. It is possible that there are human subpopulations with special sensitivity to benzene's toxic effects. If so, this could effect risk assessment and regulation related to benzene. This concern makes genetic polymorphisms in factors that influence susceptibility and benz-ene's interaction with other possible exposures into areas that might merit support in the future. It was thought that Tony cox's work on the BBRA model deserved continuing funding on the condition that he work closely with Irons and other benzene investigators. Efforts should be made, however, to-make his reports and presentations more comprehensible to his audience. On the short term, WSPA has just given Kenny Crump fi-nal direction on the elements -to be included in his reanalysi-s- of the Pliofilm cohort. His results should be forthcoming in about a month. After a review by the BTF's math and modeling subgroup, Crump will be asked to present his findings to the entire~TF, hopefully on a trip that can be coordinated with his making a similar presentation at EPA some time in November. Kenny Crump indicated that he would feel increasingly j~tified in applying a non-linear model for low-dose extrapolation from the_human data if the basic biology researchers continued to document the-existence of non-linear components in the mechanisms defining leukemogenesis. He suggested focusing their research on the step(sJ that are probably most non-linear, and so might impose a ufunctional threshold on the process, rather than endeavoring to describe the entire pathway(s) in detail. In order to provide further justification forCrump's use of a non-linear model in the report to be presented to EPA (and also to ACGIH in the winter), the 2 October 21, 1992 BP-00011899 6' l.~ ' .; r staff w~ll prepare a support document arguing, now primarily on a theoretical level, that non-linear elements occur and explaining how this non-linear effect is compounded b~ the multitude of biological processes intervening between benzene exposure and the production of a leukemia. Review of this document and Ehe additional exemplary material will be sought from the researchers currently working on benzene for API. Mary Burr Paxton, Ph.D. 3 October 21, 1992 BP-00011900