Identification of compounds contributing to glucocorticoid activity in indoor dust supported by orthogonal...

Indoor dust contains various endocrine-disrupting contaminants, yet the effect drivers of observed glucocorticoid activity are completely unknown. This study conducted an effect-directed analysis using orthogonal fractionation to identify effect drivers of glucocorticoid activity in indoor dust. After the detection of bioactivity using a human cell line stably transfected with a reporter gene, the sample underwent parallel HPLC fractionations with octadecyl, pentafluorophenyl, and aminopropyl columns to obtain orthogonal fractions. The bioassays were utilized to screen the fractions and guide efforts towards prioritization of the bioactive chemicals using targeted and non-targeted analysis with LC-HRMS. The glucocorticoid activity of the identified potential candidates was confirmed by their testing in the same bioassay. To assess their contribution to the detected mixture effects, we calculated their relative potencies. This approach led to the identification of two pharmaceuticals, clobetasol propionate and mometasone furoate, at concentrations ranging from ng to μg per gram of dust, which together accounted for up to 77% of the observed glucocorticoid activity. This is the first report documenting the effect drivers of glucocorticoid receptor agonism in indoor dust; however, together with previous studies of various environmental samples, it documents that in cases when glucocorticoid receptor-agonistic activity is detected, drugs should be considered as likely relevant contaminants. The discovery of potent drugs in household dust highlights concerns for individuals exposed within domestic environments and emphasizes the need to consider pharmaceuticals as relevant contributors to indoor contamination.