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.