Use of high-throughput screening results to prioritize chemicals for potential adverse biological effects within a West Virginia watershed

Utilizing High-Throughput Screening Data, Integrative Toxicological Prioritization Index Score, and Exposure–Activity Ratios for Chemical Prioritization: A Case Study of Endocrine-Active Pesticides in Food Crops

“…The 3R principle in animal research (i.e., replacement, reduction, and refinement) has driven the development of new approach methodologies (NAMs), such as in vitro cell-based models, − HTS assays, , and in silico modeling, which can eventually be incorporated into the health risk assessment and chemical prioritization. Indeed, the publicly available HTS data from ToxCast and Tox21 programs have been used to prioritize chemicals in the environment and ecosystem. ,− A risk-based prioritization allows for the regulatory agencies to distribute resources on the concerning chemicals for more in-depth risk assessments and cost-effective management. For the first time, this study used state-of-the-art computational tools in exposure science and toxicology and applied the EAR profiling to prioritize the endocrine-active pesticides in food crops for the Taiwanese and U.S. populations.…”

A Comprehensive Statewide Spatiotemporal Stream Assessment of Per- and Polyfluoroalkyl Substances (PFAS) in an Agricultural Region of the United States

“…49,50 An EAR of ≥0.001 has been previously used to identify samples of potential environmental concern. 51,52 ■ RESULTS AND DISCUSSION At least one PFAS was detected in 26 of the 119 stream samples (22%) and in all four (100%) of the effluent samples collected, with 10 PFAS detected overall (Table S3). All detected PFAS were PFAAs that are known to be environmentally stable.…”

“…While no individual PFAS had an EAR of >1.0 (Figure S4), a level shown to trigger observed adverse biological activity, five stream sites did have at least one EAR of >0.001, the precautionary effect screening threshold. 51,52 These five stream locations had a wide range of basin sizes (3.87−35500 km 2 ) with three locations derived from WWTP effluent-affected streams. Both wastewater effluents sampled had at least one EAR of >0.01 (Figure S4), indicating that wastewater discharge is likely an influential source of PFAS at levels of potential environmental concern to the sampled streams during this spatiotemporal study.…”

Coupling Suspect and Nontarget Screening with Mass Balance Modeling to Characterize Organic Micropollutants in the Onondaga LakeThree Rivers System

“…(B) Percent contributions of the site-specific cumulative EARs for seven OMPs (ΣEARs_ 7 OMPs ) to the site-specific cumulative EARs for 55 OMPs (ΣEARs) included in the ToxCast and Tox21 high-throughput screening database. [58][59][60][61][62][63] Error bars represent the propagated errors associated with EAR calculations. The green dashed line represents the mean percent contribution of 95±10%.…”

“…59 Chemical-assay combinations with the following data quality flags were excluded: "only highest concentration above baseline, active", "only one concentration above baseline, active", "noisy data", "borderline active", "gain AC50 < lowest concentration & loss AC50 < mean concentration", and "biochemical assay with < 50% efficacy". [58][59][60] Endpoints categorized as "background measurement", "cell morphology", "cell cycle", and "undefined" were also excluded from the calculation. 59 (C) ∑EARs for four clusters of OMPs (i.e., Cluster A, B, C, and D).…”