In vitro approaches to developmental neurotoxicity

This chapter discusses the in vitro approaches to developmental neurotoxicity. Neurotoxicity can be defined as any adverse effect on the chemistry, structure or function of the nervous system, induced by chemical or physical influences. A substance is defined as neurotoxic when it or its metabolites produce adverse effects as a result of direct interactions with the nervous system. The specific effects of the chemical on the nervous system can be detected in the course of standard toxicity testing such as developmental neurotoxicity (DNT) testing. The development of alternative in vitro models such as mammalian cells in culture or non-mammalian model systems could serve as tools for neurotoxicity and developmental neurotoxicity testing. Several issues need to be considered while choosing the mammalian cells in culture model for neurotoxicity testing such as limited lifespan, variability among different cultures, problems of purity and the need of particular attention during preparation and culturing etc. However, the in vitro systems are amenable and very useful for mechanistic studies at the cellular and molecular level and also provide a rapid, relatively inexpensive, and reliable way for screening chemicals for potential neurotoxicity and/or developmental neurotoxicity. A number of alternative non-mammalian models such as Zebrafish and C. elegans have been used to assess environmental toxicity. Finally, a battery of alternative testing models for neurotoxicity is not expected to fully replace current in vivo animal testing without efforts by regulatory agencies, institutions, foundations and private entities worldwide.