Study design considerations in developmental neurotoxicology.

It is widely accepted that exposure to environmental factors during development can result in effects other than death, gross structural abnormality, or altered growth. One area of concern is the developing nervous system, which may be especially vulnerable to environmental perturbation. Testing chemicals for potential developmental neurotoxicity has received a high priority and testing guidelines have been published and recently revised by the U.S. Environmental Protection Agency. These guidelines are based on several principles of developmental neurotoxicity that have been developed during several years of research. In general, manifestation of neurotoxicity following developmental exposure can depend on the time at which exposure occurs and for the purposes of hazard detection, experiments should be designed to optimize the detection of neurotoxicity. In addition, maternal health and interaction with the offspring, as well as postnatal development are important design issues in developmental neurotoxicology. It is also widely accepted that several doses be used and multiple measures of neurotoxicity assessed in both genders at several points during the life span of the animal. Finally, the litter is usually regarded as the most appropriate statistical unit to control for genetic and maternal factors.