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/pharmacodynamics; 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 physicochemical, pharmacokinetic, and pharmacodynamic properties of the agent with the genotypic features of the test organism.
Nelson
B K
BK
National Institute for Occupational Safety and Health, Division of Biomedical and Behavioral Science, Cincinnati, OH 45226.
D000375:Aging / Q000187:drug effects*; D000818:Animals; D001711:Biotransformation; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D009420:Nervous System / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D009498:Neurotoxins / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D012107:Research Design; D013723:Teratogens / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*
D009498:Neurotoxins; D013723:Teratogens