Expanding the test set: Chemicals with potential to disrupt XXXX brain development.

@entity1 @entity137 @entity2359
UNASSIGNED: High-throughput test methods including molecular, cellular, and alternative species-based assays that examine critical events of normal brain development are being developed for detection of developmental neurotoxicants. As new assays are developed, a "training set" of chemicals is used to evaluate the relevance of individual assays for specific endpoints. Different training sets are necessary for each assay that would comprise a developmental @entity2359 test battery. In contrast, evaluation of the predictive ability of a comprehensive test battery requires a set of chemicals that have been shown to alter brain development after in vivo exposure ("test set"). Because only a small number of substances have been well documented to alter @entity1 neurodevelopment, we have proposed an expanded test set that includes chemicals demonstrated to adversely affect neurodevelopment in animals. To compile a list of potential developmental neurotoxicants, a literature review of compounds that have been examined for effects on the developing nervous system was conducted. The search was limited to @entity1 studies published in the peer-reviewed literature and regulatory studies submitted to the U.S. EPA. The definition of developmental @entity2359 encompassed changes in behavior, brain morphology, and neurochemistry after gestational or lactational exposure. Reports that indicated developmental @entity2359 was observed only at doses that resulted in significant maternal @entity137 or were lethal to the fetus or offspring were not considered. As a basic indication of reproducibility, we only included a chemical if data on its developmental @entity2359 were available from more than one laboratory (defined as studies originating from laboratories with a different senior investigator). Evidence from @entity1 studies was included when available. Approximately 100 developmental @entity2359 test set chemicals were identified, with 22% having evidence in @entity1 .
