BIOLOGICALLY-BASED, QUANTITATIVE RISK ASSESSMENT OF NEUROTOXICANTS

The need for biologically based, quantitative risk assessment procedur es for noncancer endpoints such as neurotoxicity has been discussed in reports by the United States Congress (Office of Technology Assessmen t, OTA), National Research Council (NRC), and a federal coordinating c ouncil. According to OTA, current attention and resources allocated to health risk assessment research are inadequate and not commensurate w ith its impact on public health and the economy. Methods to include co ntinuous rather than dichotomous data for neurotoxicity endpoints, bio markers of exposure and effects, and pharmacokinetic and mechanistic d ata have been proposed for neurotoxicity risk assessment but require f urther review and validation before acceptance, The purpose of this sy mposium was to examine procedures to enhance the risk assessment proce ss for neurotoxicants and to discuss techniques to make the process mo re quantitative, Accordingly, a review of the currently used safety fa ctor risk assessment approach for neurotoxicants is provided along wit h specific examples of how this process may be enhanced with the use o f the benchmark dose approach. The importance of including physiologic ally based pharmacokinetic data in the risk assessment process and spe cific examples of this approach is presented for neurotoxicants. The r ole of biomarkers of exposure and effect and mechanistic information i n the risk assessment process are also addressed, Finally, quantitativ e approaches with the use of continuous neurotoxicity data are demonst rated and the outcomes compared to those generated by currently used r isk assessment procedures. (C) 1996 Society of Toxicology.