Biologically based, quantitative risk assessment of neurotoxicants.
The need for biologically based, quantitative risk assessment procedures for noncancer endpoints such as neurotoxicity has been discussed in reports by the United States Congress (Office of Technology Assessment, OTA), National Research Council (NRC), and a federal coordinating council. According to OTA, current attention and resources allocated to health risk assessment research are inadequate and not commensurate with its impact on public health and the economy. Methods to include continuous rather than dichotomous data for neurotoxicity endpoints, biomarkers of exposure and effects, and pharmacokinetic and mechanistic data have been proposed for neurotoxicity risk assessment but require further review and validation before acceptance. The purpose of this symposium was to examine procedures to enhance the risk assessment process for neurotoxicants and to discuss techniques to make the process more quantitative. Accordingly, a review of the currently used safety factor risk assessment approach for neurotoxicants is provided along with specific examples of how this process may be enhanced with the use of the benchmark dose approach. The importance of including physiologically based pharmacokinetic data in the risk assessment process and specific examples of this approach is presented for neurotoxicants. The role of biomarkers of exposure and effect and mechanistic information in the risk assessment process are also addressed. Finally, quantitative approaches with the use of continuous neurotoxicity data are demonstrated and the outcomes compared to those generated by currently used risk assessment procedures.
Slikker
W
W
Division of Neurotoxicology, National Center for Toxicological Research/Food and Drug Administration, Jefferson, Arkansas 72079, USA.
Crump
K S
KS
Andersen
M E
ME
Bellinger
D
D
D015415:Biomarkers / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006077:Government Agencies; D006801:Humans; D008954:Models, Biological; D009420:Nervous System / Q000187:drug effects*; D009422:Nervous System Diseases / Q000139:chemically induced*; D009498:Neurotoxins / Q000493:pharmacokinetics / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment
D015415:Biomarkers; D009498:Neurotoxins