In vitro and alternative approaches to developmental neurotoxicity

In recent years, the need to develop acceptable alternatives to conventional animal testing for neurotoxicity and developmental neurotoxicity has been increasingly recognized. Hence efforts are being directed toward the development of alternative models, utilizing either mammalian cells in culture or nonmammalian model systems. Such in vitro testing procedures have the purposes of investigating mode and/or mechanism of action of chemicals, particularly related to early, upstream events in the neurotoxic process and of screening chemicals of unknown toxicity to flag compounds for further in vitro and in vivo neurotoxicity studies. Several cell culture models exist, with different levels of complexity, and a major issue of debate remains that of the end points of toxicity to be measured. Screening for developmental neurotoxicity may require additional specific end points. Promising nonmammalian models include zebrafish and Caenorhabditis elegans. These issues are discussed in this chapter, together with considerations for further developments and validation of alternative models.