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Developmental neurotoxicity assessments: selecting exposure parameters.
Congenit Anom 1992 Mar; 32(Suppl 1):S31-S41
The selection of dosing regimens in studies of neurotoxicity was discussed. The author recommends consideration of six primary factors in the determination of dosing regimens for neurotoxicity assessments, whether a single dose is employed during pregnancy, or a continuous exposure from prepregnancy through postnatal development. These included defining the purpose of the study, examining pharmacokinetic and pharmacodynamic properties of the test compound, consideration of the biotransformation properties of the test compound, consideration of genetic and species variables in test animals, examination of limiting factors, and consideration of miscellaneous factors such as maternal toxicity and the origin and selectivity of the effects. Factors to be considered in the determination of single versus multiple exposures were examined by reviewing the literature on limited and extended exposure studies. The use of pharmacokinetic modeling in developmental neurotoxicology studies was discussed.
NIOSH-Author; Laboratory-animals; Neurotoxic-effects; Comparative-toxicology; Toxic-dose; Acute-exposure; Long-term-exposure; Teratology
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