Toxic responses of the fish nervous system

Few of the approximately 70,000 chemicals on the Toxic Substances Control Act inventory or the 1000 to 1600 new chemicals introduced each year in the United States have been tested for neurotoxicity to support risk assessments (NRC, 1992), even though it is estimated that 5 to 10% of them are likely to be neurotoxic. Neurotoxicity has been defined as adverse effects of physical, biological, or chemical agents on the structure or function of the nervous system in developing or adult organisms (Philbert et al., 2000). From a human health risk assessment perspective, the potential for neurotoxic effects associated with synthetic chemicals has led to the development of valid, sensitive, and reproducible methods to identify neurotoxic chemicals, to characterize neurological effects, and to determine the mechanisms by which chemicals produce neurotoxicity. Similar efforts to develop methods for assessing neurotoxicity in fish may yield further insights into neurotoxic mechanisms (Carlson et al., 1998; Drummond and Russom, 1990; Featherstone et al., 1991, 1993; Rice et al., 1997; Timme-Laragy et al., 2006; Weber et al., 1997) in addition to addressing ecological risk concerns. This chapter aims to provide a framework from which to approach questions concerning the neurotoxic effects of chemicals in fish. First, a brief summary of structural and functional attributes of the nervous system is provided, followed by an overview of neurotoxic mechanisms of action. The final section of the chapter summarizes mechanisms of action and manifestations of neurotoxic effects for several classes of compounds. In this latter section, an attempt is made to highlight examples where structural and functional alterations to the nervous system at the subcellular to cellular level can be linked to physiological and behavioral effects. The integration of effects across levels of biological organization is essential for establishing the mechanistic basis underlying neurotoxicity, as well as for identifying and quantifying ecologically relevant neurotoxic effects in fish.