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Selecting exposure parameters in developmental neurotoxicity assessments.
Neurotoxicol Teratol 1991 Nov; 13(6):569-573
Factors used when selecting the exposure/dosing regimen and duration for developmental neurotoxicity investigations were described, and discussed. The discussion focused on: evaluation of a study's purpose with respect to risk assessment, hazard identification, or investigation of teratogenic mechanisms; investigation of the physicochemical properties of the test compound (molecular parameters, degree of ionization, solubility) and pharmacokinetic factors (absorption rate and extent, tissue distribution, transport, elimination, biotransformation); assessment of the biotransformation ability of compounds; consideration of genotypic variabilities of test species along with limiting factors; and review of miscellaneous factors. Examples of discrete versus extended dosing periods were provided and the use of pharmacokinetic modeling was mentioned. The authors conclude that the neurotoxicity of a single large dose of an exogenous agent versus a series of smaller doses depends on the interplay between physicochemical, pharmacokinetic, and pharmacodynamic factors and the test organism's genotypic features.
NIOSH-Author; Dose-response; Exposure-methods; Neurotoxicology; Teratology; Pharmacodynamics; Genetic-factors; Neurotoxic-effects; Exposure-levels
Issue of Publication
Neurotoxic Disorders; Neurotoxic-effects
Neurotoxicology and Teratology
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Content source: National Institute for Occupational Safety and Health Education and Information Division