The concern for developmental neurotoxicology: is it justified and what is being done about it?

In general, it is believed that the possibility of an adverse developmental outcome following conception is relatively high. In most cases, the cause of the defect is not clear, although exposure to chemical agents at a critical period during development has been proposed to play a significant role. Consequently, regulatory agencies such as the U.S. Environmental Protection Agency (U.S. EPA) have promulgated testing guidelines for assessing developmental neurotoxicity of chemicals in animal testing protocols. Concerns have been expressed about the use of behavioral tests to evaluate chemicals for developmental neurotoxicity, since some investigators believe that they lack predictive validity for human developmental neurotoxicity. Other investigators have indicated that results from such studies are difficult to interpret because of a lack of standardization and sensitivity of the tests. Furthermore, it has been argued that the developing organism is not especially sensitive to chemicals or, if effects are observed, the developing organism is capable of compensating for the deficit. Recent research, however, has adequately demonstrated that developing organisms are especially vulnerable to chemical agents if the exposure occurs at a critical period during development, while other studies have supported the assumption that functional or behavioral effects observed in animal models can be extrapolated to humans. These findings support the routine assessment of chemicals for developmental neurotoxicity using functional end points and suggest that currently available methods could be used to determine more precisely the mechanism of chemical-induced developmental defects.