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Building a Database of Developmental Neurotoxitants: Evidence from Human and Animal Studies
PADILLA, S. J., W. R. MUNDY, T. J. SHAFER, M. E. GILBERT, J. BREIER, J. COWDEN, K. M. CROFTON, D. W. HERR, K. F. JENSEN, K. RAFFAELE, N. RADIO, AND K. SCHUMACHER. Building a Database of Developmental Neurotoxitants: Evidence from Human and Animal Studies. Presented at Society of Toxicology Annual Meeting, Baltimore, MD, March 15 - 19, 2009.
EPA’s program for the screening and prioritization of chemicals for developmental neurotoxicity (DNT) necessitates the generation of a list of chemicals that are known mammalian developmental neurotoxicants. This chemical list will be used to evaluate the sensitivity, reliability, and predictive power of alternative DNT assays. A literature review was conducted for > 400 compounds that have been suggested as developmental neurotoxicants. Compounds were assigned to one of three groups based on the strength of the evidence for DNT: (1) no evidence: no reports meeting our criteria for evidence or reports showing no DNT; (2) minimal evidence: one report or multiple reports from a single laboratory; or (3) substantial evidence: reports from more than one laboratory. Evidence was defined as (a) mammalian (laboratory animal or human) studies published in the peer-reviewed literature and/or (b) studies submitted to the EPA. Studies on chemical mixtures, in vitro studies, reports where > 5 g/kg of the chemical was administered, and reports with inappropriate statistical analyses were excluded. The definition of neurotoxicity was broad, encompassing gross structural changes (e.g., reduced brain weight, spina bifida, exencephaly) to more subtle indices of DNT (e.g., changes in brain morphometry, neurochemical imbalances, and behavioral impairments). Of the chemicals examined, ~ 50% were assigned to the 'no evidence' of developmental neurotoxicity group; ~25% had minimal evidence; and the remaining 25% had substantial evidence of toxicity to the developing nervous system. The chemicals in the latter group will be especially useful for vetting protocols that have been proposed as screens for DNT. (This abstract does not necessarily reflect Agenc