Principles of developmental neurotoxicology

With 4-8 percent of U.S. children exhibiting anatomical and/or functional deficits, and the occurrence of several tragic clinical syndromes resulting from developmental exposure to such agents as ethanol, lead and methylmercury, there is good reason to focus attention on the principles of developmental neurotoxicology. Various animal models have been used to confirm the developmental neurotoxicity that results from exposure to these agents, and along with clinical evidence, have implicated several other chemical classes such as antimitotics, insecticides, polyhalogenated hydrocarbons, psychoactive drugs, solvents and vitamins as specific agents with developmental neurotoxic potential. As for developmental toxicity in general, the nature and extent of neurotoxic effects are often dependent on the timing of exposure, and because stages of nervous system development can vary significantly between species in relation to the time of birth, variations in neurotoxic outcome across species are expected. There are several instances in which functional alterations (e.g., neuromotor development, locomotor activity, reactivity and/or habituation, learning and memory and sensory system modulation) have been observed at doses below those needed to produce other indicators of developmental toxicity. Neuroanatomical/neurohistological, neurochemical and neurophysiological endpoints have been used to substantiate these functional deficits and/or to describe adverse nervous system effects in the absence of functional data. As knowledge about the toxicological mechanisms underlying the expression of developmental neurotoxicity is increased, the ability to conduct quantitative risk assessments and protect human health will be enhanced.