Global occurrence of synthetic glucocorticoids and glucocorticoid receptor agonistic activity, and aquatic hazards in effluent discharges and freshwater systems

With a growing global population comes an increase in pharmaceutical usage and a concentration of pharmaceutical consumption in urban areas, which release diverse chemicals and waste to the environment. Because synthetic glucocorticoids have been identified as endocrine disruptors and environmental contaminants of emerging concern, we conducted a global scanning assessment of these pharmaceuticals in wastewater effluents and freshwater systems. Thirty-seven synthetic glucocorticoids were identified, and available information on environmental occurrence of specific substances was critically reviewed from the peer-reviewed literature. We developed probabilistic environmental exposure distributions for synthetic glucocorticoids, and further considered glucocorticoid receptor agonistic activity from biomonitoring efforts using in vitro methods. When sufficient data was available, we then performed probabilistic environmental hazard assessments using predicted no effect concentrations, therapeutic hazard values and in vitro bioactivity information (AC50 values) for specific glucocorticoids. We observed pronounced differences for aquatic monitoring data among geographic regions; information is not available from many regions where most of the global population resides. We identified differences between analytical chemistry derived occurrence values for specific chemicals and biomonitoring results from seven different in vitro assays, which suggests that compounds not previously preselected for targeted analyses contribute to glucocorticoid receptor agonism in effluent discharges and aquatic systems. Our observations further identify the importance of advancing nontargeted analyses and research on in vitro to in vivo extrapolation of aquatic hazards. Though aquatic toxicology information is lacking for most of these substances, we observed diverse aquatic hazards for several synthetic glucocorticoids, and these observations varied by aquatic matrix and among geographic regions. This study identifies timely data gaps and can inform future environmentally relevant chemistry and toxicology efforts examining synthetic glucocorticoids in aquatic systems.