NEUROTOXICITY MODELING FOR RISK ASSESSMENT

The setting of acceptable exposure levels for neurotoxicants has follo wed the traditional approach of dividing experimental no-observed-adve rse-effect-levels (NOAELs) by safety/uncertainty factors. NOAELs are b elieved by many toxicologists to represent levels having zero or negli gible risk, while uncertainty factors are used to account for a number of sources of variation. Although the use of NOAELs in this manner ha s been criticized because of their imprecise quantitative definition, NOAELs for nonquantal neurotoxic effects have not been replaced by mor e precisely defined quantities (e.g., benchmark doses), partly due to the absence of a generally accepted methodology for attaching specific risk levels to low exposures. The present paper describes a quantitat ive approach to modeling nonquantal neurotoxic effects for risk assess ment, which can be used to obtain results similar to the familiar resu lts obtained in risk assessment for carcinogenicity and developmental toxicity. The steps involved in implementing the process are discussed , with particular attention being given to the critical step of defini ng an adverse neurologic effect. An experimental data set is used to i llustrate the methodology. (C) 1995 Academic Press, Inc.