INTRODUCTION: The U.S. Environmental Protection Agency's (EPA's) @entity137 Forecaster (ToxCast) is a potential tool for chemical prioritization, hazard identification, and risk assessment. We conducted a case study to compare ToxCast data with endpoints from other in vitro and in vivo studies for two data-rich pesticides: @entity1304 and @entity22771 . METHODS: ToxCast assays for endocrine disruption, development ( @entity3392 ), and @entity2359 were qualitatively compared to traditional @entity2359 , developmental and reproductive @entity137 findings. We also used in vitro-in vivo extrapolation to convert half-maximal activity concentrations in active ToxCast assays to @entity35 oral equivalent doses, and quantitatively compared these to the lowest observable effect level (LOEL) from in vivo studies. RESULTS: @entity1304 was inactive for GABAA R, unlike in vivo; but active with @entity935 transporter assays and was @entity2359 in @entity3392 as expected. @entity22771 was not active for these endpoints in vivo or in vitro. @entity14057 inhibition was ToxCast-inactive, although both pesticides are inhibitors in vivo. ToxCast results were generally inactive for @entity1304 @entity172 receptor agonism and @entity342 receptor antagonism unlike in vivo. Calculated oral equivalent doses for @entity172 receptor and @entity342 receptor pathways and for @entity3392 assays for both compounds were generally consistent with in vivo LOELs. @entity1304 showed @entity2359 and both pesticides showed developmental effects in the @entity3392 assays, although @entity22771 is not developmentally toxic in vivo. CONCLUSIONS: ToxCast's predictions showed concordance on some endpoints and nonconcordance, consisting mainly of false inactives, in several critical endpoints, likely due to a lack of metabolic activation and limitations in assay design. @entity3392 assays were good predictors of developmental @entity137 and @entity2359 for @entity1304 .

A Comparison of ToxCast Test Results with In Vivo and Other In Vitro Endpoints for Neuro, Endocrine, and Developmental @entity137 : A Case Study Using XXXX and @entity22771 .

@entity172 :: ('MESH:D004967', 'Chemical') :: ['estrogen'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'Toxicity'] @entity22771 :: ('MESH:C005828', 'Chemical') :: ['methidathion', 'Methidathion'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity1304 :: ('MESH:D004726', 'Chemical') :: ['endosulfan', 'Endosulfan'] @entity14057 :: ('114549(Tax:7955)', 'Gene') :: ['Acetylcholinesterase'] @entity342 :: ('CHEBI:50113', 'Chemical') :: ['androgen'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity3392 :: ('7955', 'Species') :: ['Zebrafish', 'zebrafish'] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity', 'neurotoxic']
@entity1304 :: (MESH:D004726,Chemical) :: ['Endosulfan']
