Risk assessment for neurobehavioral toxicity.

Abstract

A study by the National Academy of Sciences/National Research Council (NAS/NRC) found neurobehavioral toxicity to be one of the areas where almost no data are available for the assessment of toxicity. Using the NAS/NRC report and a data base from the American Conference of Government Industrial Hygienists (ACGIH), an estimate of the number of neurobehavioral toxins in commercial chemicals can be made. Although the assumption made in making such a calculation may be invalid, the exercise suggests that the number of neurobehavioral toxins may be quite large. There does seem to be general agreement as to what type of neurobehavioral test procedures are appropriate for regulatory purposes. Select committees have consistently recommended the use of test batteries that include schedule-controlled behavior, motor activity, and neuropathological examination following in vivo perfusion, for regulatory purposes. Alkyltin data developed from such a battery were applied to the risk assessment model employed by the United States Environmental Protection Agency (EPA) in their calculations of acceptable daily intake. Using this test battery and the EPA risk assessment model, the acceptable daily intake calculated is of the same order of magnitude as the total limit values established by the ACGIH. A number of special issues in neurobehavioral toxicity also are discussed, including the definition of adverse neurobehavioral toxic effects, species extrapolation, correlation of behavior and neuropathology, alternative methods, and quality of life issues.