An integrative approach to neurotoxicology

Exposure of human populations to a wide variety of chemicals has generated concern about the potential neurotoxicity of new and existing chemicals. Ex perimental studies conducted in laboratory animals remain critical to the s tudy of neurotoxicity. An integrative approach using pharmacokinetic, neuro pathological, neurochemical, electrophysiological, and behavioral methods i s needed to determine whether a chemical is neurotoxic. There are a number of factors that can affect the outcome of a neurotoxicity study, including the choice of animal species, dose and dosage regimen, route of administrat ion, and the intrinsic sensitivity of the nervous system to the test chemic al. The neurotoxicity of a chemical can vary at different stages of brain d evelopment and maturity. Evidence of neurotoxicity may be highly subjective and species specific and can be complicated by the presence of systemic di sease. The aim of this paper is to give an overview of these and other fact ors involved in the assessment of the neurotoxic potential for chemicals. T his article discusses the neurotoxicity of several neurotoxicants (eg, acry lamide, trimethyltin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, mangane se, and ivermectin), thereby highlighting a multidisciplinary approach to t he assessment of chemically induced neurotoxicity in animals. These model c hemicals produce a broad range of effects that includes peripheral axonopat hy, selective neuronal damage within the nervous system, and impaired neuro nal-glial metabolism.