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Well-respected leaders in the field of in vitro neurotoxicology take a fresh look at their own and other's work, critically and comparatively analyzing it across experimental systems and toxicants, and synthesizing essential principles for in vitro neurotoxicity testing. Neurotoxicants of significance to human health are emphasized, especially those for which metabolism and dose-responses are well well studied both in vivo and in vitro: lead, mercury, organophosphorous insecticides, polychlorinated biphenyls and dioxin, ethanol, and endogenous proteins. The goal is to set out new concepts and research directions that will hasten significant improvement in the methods and systems for in vitro neurotoxicity testing. Neurotoxicity assessment with in vitro systems offers not only a means to better understand mechanisms of action of toxicants and decrease reliance on laboratory animals, but also provides a basis for reliable, high throughput screening of new and untested chemicals. In In Vitro Neurotoxicology: Principles and Challenges, well-respected leaders in the field take a fresh look at their own and others' work, critically and comparatively analyzing it across experimental systems and toxicants, and synthesizing essential principles for in vitro neurotoxicity testing. In thematically organized chapters, the authors employ examples comprised of multiple experimental systems and endpoints, and discuss the use of complementary in vivo/in vitro strategies. Neurotoxicants of significance to human health are emphasized, especially those for which metabolism and dose-responses are well studied both in vivo and in vitro: lead, mercury, organophosphorus insecticides, polychlorinated biphenyls and dioxin, ethanol, and endogenous proteins. Several neurotoxicology topics covered provide insight into neurodevelopmental and neurodegenerative diseases, including the concept of astroglia as depots for lead and other metals in the central nervous system, the elucidation of factors involved in the onset of puberty in females, and the exploration of endogenous proteins as neurotoxicants. §Authoritative and forward-looking, In Vitro Neurotoxicology: Principles and Challenges sets out new concepts and research directions that will facilitate significant improvement in today's methods and systems for in vitro neurotoxicity testing.