Neurotoxicity testing: a discussion of in vitro alternatives

A large number of chemicals may exert adverse effects on the central and/or peripheral nervous system. A commonly recommended strategy for neurotoxicity testing is that of a tiered approach aimed at identifying and characterizing the neurotoxicity of a compound. Guidelines exist in the United States and other countries that define the tests to be utilized in tier 1 testing. To address problems related to the increasing cost and time required for toxicity testing, the increasing number of chemicals being developed, and the concern of animal welfare activists, attention is currently being devoted to in vitro alternatives. This paper addresses the use of in vitro systems in neurotoxicology, and their potential role in a general strategy for neurotoxicity testing. The advantages and disadvantages of in vitro approaches for mechanistic studies and for screening of neurotoxicants are discussed. Suggestions for further validation studies are proposed.