Towards quantitative risk assessment for neurotoxicity

Methods for quantitative risk assessment have been developed in some detail for carcinogens. These methods attempt to be consistent with current knowledge about the mechanism of carcinogenesis and are probably not applicable to neurotoxicity endpoints. The traditional approach for neurotoxicants has been to define the NOAEL (No Observed Adverse Effects Level) or LOAEL (Lowest Observed Adverse Effects Level) and to divide by a safety factor. One of the weaknesses of this approach is that it does not yield a risk estimate; however, this approach has been widely used, and it is consistent with very limited data. Alternative methods to assess risk are available and have been applied to existing data. These methods are very much dependent upon the nature of the data analyzed, but current data are often limited and do not allow good and comprehensive risk assessments of neurotoxic endpoints. Additional experiments and expanded experimental designs can facilitate improved and more precise risk assessments. Experiments should consider dose ranges which encompass conceivable environmental exposures. Experiments should measure and report individual, as well as group response, and indices of exposure. Finally, more work needs to be done to compare responses across several species. More comprehensive experiments can only lead to more comprehensive risk assessments.