SELECTING EXPOSURE PARAMETERS IN DEVELOPMENTAL NEUROTOXICITY ASSESSMENTS

Numerous factors must be considered in selecting exposure parameters for developmental neurotoxicity investigations. Whether employing a single dose during pregnancy, or continuous exposure from prepregnancy through early postnatal developmental periods, the following primary factors should be addressed: 1) Purpose of the study; 2) pharmacokinetics/pharmaco-dynamics; 3) biotransformation; 4) genotypic variables; 5) limiting factors, including the availability of test compounds for evaluation; and 6) several general, miscellaneous factors. Whether a single, large dose of an exogenous agent is more toxic to the developing nervous system than a series of smaller doses depends upon the interaction of the physiochemical, pharmacokinetic, and pharmacodynamic properties of the agent with the genotypic features of the test organism.