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In 2007 the United States National Research Council (NRC) published a vision for toxicity testing in the 21st century that emphasized the use of in vitro high‐throughput screening (HTS) methods and predictive models as an alternative to in vivo animal testing. In the present study we examine the state of the science of HTS and the progress that has been made in implementing and expanding on the NRC vision, as well as challenges to implementation that remain. Overall, significant progress has been made with regard to the availability of HTS data, aggregation of chemical property and toxicity information into online databases, and the development of various models and frameworks to support extrapolation of HTS data. However, HTS data and associated predictive models have not yet been widely applied in risk assessment. Major barriers include the disconnect between the endpoints measured in HTS assays and the assessment endpoints considered in risk assessments as well as the rapid pace at which new tools and models are evolving in contrast with the slow pace at which regulatory structures change. Nonetheless, there are opportunities for environmental scientists and policymakers alike to take an impactful role in the ongoing development and implementation of the NRC vision. Six specific areas for scientific coordination and/or policy engagement are identified. Environ Toxicol Chem 2019;38:12–26. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. [ABSTRACT FROM AUTHOR]

ABSTRACT Coal-fly ash was released in unprecedented amounts (4.1 × 106 m3) into the Emory River from the Tennessee Valley Authority Kingston Fossil Plant on Watts Bar Reservoir in Tennessee. Tree swallows were exposed to ash-related constituents at the ash release via their diet of emergent aquatic insects, whose larval forms can accumulate constituents from submerged river sediments. Reproduction of tree swallow colonies was assessed over a 2-year period by evaluating whether 1) ash constituent concentrations were elevated in egg, eggshell, and nestling tissues at colonies near ash-impacted river reaches compared to reference colonies, 2) production of fledglings per nesting female was significantly lower in ash-impacted colonies versus reference colonies, and 3) ash constituent concentrations or diet concentrations were correlated with nest productivity measures (clutch size, hatching success, and nestling survival, and fledglings produced per nest). Of the 26 ash constituents evaluated, 4 (Se, Sr, Cu, and Hg) were significantly elevated in tissues potentially from the ash, and 3 (Se, Sr, and Cu) in tissues or in swallow diet items were weakly correlated to at least one nest-productivity measure or egg weight. Tree swallow hatching success was significantly reduced by 12%, but fledgling production per nest was unaffected due to larger clutch sizes in the impacted than reference colonies. Bioconcentration from the ash to insects in the diet to tree swallow eggs appears to be low. Overall, adverse impacts of the ash on tree swallow reproduction were not observed, but monitoring is continuing to further ensure Se from the residual ash does not adversely affect tree swallow reproduction over time. Integr Environ Assess Manag 2015;11:56-66. © 2014 SETAC [ABSTRACT FROM AUTHOR]

ABSTRACT Current scientific advances in metal and metalloid risk assessment were applied to evaluate risk to aquatic and riparian wildlife species potentially impacted by residual coal fly ash after cleanup of an unprecedented large ash release into an aquatic environment-the first assessment of its kind. Risk was evaluated using multiple lines of evidence (LOE), including 1) tissue-based risk assessment of inorganic concentrations in piscivorous and insectivorous bird eggs and raccoon organs, 2) deterministic and probabilistic diet-based risk estimates for 10 receptors species, 3) raccoon health metrics, and 4) tree swallow nest productivity measures. Innovative approaches included use of tissue-based toxicity reference values (TRVs), adjustment of bioavailability in the dietary uptake models (using sequential metal extractions in sediment), partitioning chemical species into uptake compartments (e.g., prey gut, nongut, sediment), incorporating uncertainty in both modeled dose and dietary TRVs, matching TRVs to chemical forms of constituents, and pairing these LOEs with reproductive success or health status of sensitive receptor species. The weight of evidence revealed that risk to wildlife from residual ash was low and that risk, though low, was most pronounced for insectivorous birds from exposure to Se and As. This information contributes to the debate surrounding coal combustion residue regulations prompted by this ash release. Because of the responsible party's proactive approach of applying state-of-the-art methods to assess risk using several LOEs that produced consistent results, and because of their inclusion of the regulating agencies in decisions at every step of the process, the risk assessment results were accepted, and an effective approach toward cleanup protective of the environment was quickly implemented. This study highlights the value of using multiple LOEs and the latest scientific advances to assist in timely decision making to obtain an effective remedy for an emergency spill. Integr Environ Assess Manag 2015;11:67-79. © 2014 SETAC [ABSTRACT FROM AUTHOR]