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Comparative Endpoint Sensitivity of Bioanalytical Tools for Glucocorticoid Receptor Agonism Surveillance in Aquatic Matrices
Synthetic glucocorticoids, which occur globally in wastewater effluent discharges, surface waters, and reuse projects, are endocrine disruptors and contaminants of emerging concern (CECs) of relevance for water quality surveillance. Because diverse bioanalytical tools are increasingly employed as new approach methodologies for in vitro to in vivo extrapolations and water quality assessments, including for glucocorticoid receptor (GR) agonist activity, we examined endpoint sensitivities of multiple common in vitro methods. We employed probabilistic environmental hazard assessments to initially examine the likelihood of each in vitro assay identifying GR hazards in effluent discharges and surface waters. We then used chemical toxicity distributions to advance an understanding of relative sensitivity among in vitro assays by identifying the likelihood of these CECs to elicit an agonistic response at environmentally relevant concentrations. We observed commercially available and other in vitro assays reported in the refereed literature to generally be more sensitive than any of the assays included in ToxCast efforts. Our observations emphasize the importance of further studies to inform selection, use, and interpretation of endpoint responses within bioanalytical tools during in vitro to in vivo extrapolation studies and for detection of GR receptor agonist activity during water quality assessments.
We used a probabilistic approach to identify the relative endpoint sensitivity of various bioanalytical tools measuring glucocorticoid receptor agonism in water resources.
Comparative Endpoint Sensitivity of Bioanalytical Tools for Glucocorticoid Receptor Agonism Surveillance in Aquatic Matrices
Synthetic glucocorticoids, which occur globally in wastewater effluent discharges, surface waters, and reuse projects, are endocrine disruptors and contaminants of emerging concern (CECs) of relevance for water quality surveillance. Because diverse bioanalytical tools are increasingly employed as new approach methodologies for in vitro to in vivo extrapolations and water quality assessments, including for glucocorticoid receptor (GR) agonist activity, we examined endpoint sensitivities of multiple common in vitro methods. We employed probabilistic environmental hazard assessments to initially examine the likelihood of each in vitro assay identifying GR hazards in effluent discharges and surface waters. We then used chemical toxicity distributions to advance an understanding of relative sensitivity among in vitro assays by identifying the likelihood of these CECs to elicit an agonistic response at environmentally relevant concentrations. We observed commercially available and other in vitro assays reported in the refereed literature to generally be more sensitive than any of the assays included in ToxCast efforts. Our observations emphasize the importance of further studies to inform selection, use, and interpretation of endpoint responses within bioanalytical tools during in vitro to in vivo extrapolation studies and for detection of GR receptor agonist activity during water quality assessments.
We used a probabilistic approach to identify the relative endpoint sensitivity of various bioanalytical tools measuring glucocorticoid receptor agonism in water resources.
Comparative Endpoint Sensitivity of Bioanalytical Tools for Glucocorticoid Receptor Agonism Surveillance in Aquatic Matrices
Cole, Alexander R. (author) / Brooks, Bryan W. (author)
ACS ES&T Water ; 3 ; 3082-3092
2023-09-08
Article (Journal)
Electronic Resource
English
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