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Expanding the test set: Chemicals with potential to disrupt mammalian brain development
Citation:
Mundy, W., S. Padilla, J. Breier, K. Crofton, M. Gilbert, D. Herr, K. Jensen, N. Radio, K. Raffaele, K. Schumacher, Tim Shafer, AND J. Cowden. Expanding the test set: Chemicals with potential to disrupt mammalian brain development. NEUROTOXICOLOGY AND TERATOLOGY. Elsevier Science Ltd, New York, NY, 52:25-35, (2015).
Impact/Purpose:
Critical Reviews on Toxicology
Description:
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 neurotoxcants. 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 neurotoxdty test battery. In contrast, evaluation of the predictive ability of a comprehensive test battery requires a set of chemicals that have been shovvn to alter brain development after in vivo exposure ("test set"). Because only a small number of substances have been well documented to alter human neurodevebpment,we have proposed an expanded test set that includes chemicals demonstrated to adversely affect neurodevelopment in animals. To compile a list of potential developmental neurotoxcants, a literature review of compounds that have been examined for effects on the developing nervous system was conducted. The search was limited to mammalian studies published in the peer-reviewed literature and regulatory studies submitted to the U.S. EPA. The definition of developmental neurotoxicity encompassed changes in behavior, brain morphology, and neurochemistry after gestational or lactational exposure. Reports that indicated developmental neurotoxicity was observed only at doses that resulted in significant maternal toxicity 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 neurotoxdty were available from more than one laboratory (defined as studies originating from laboratories with a different senior investigator). Evidence from human studies was included when available. Approximately 100 developmental neurotoxicity test set chemicals were identified, with 22% having evidence in humans.
