Assessing Indoor Dust Interference With Human Nuclear Hormone Receptors In Cell -Based Luciferase Reporter Assays

BACKGROUND: Per- and polyfluoroalkyl substances (PEAS), organophosphate esters (OPEs), and polybrominated diphenyl ethers (PBDEs) are hormone-disrupting chemicals that migrate from building materials into air and dust.OBJECTIVES: We aimed to quantify the hormonal activities of 46 dust samples and identify chemicals driving the observed activities.METHODS: We evaluated associations between hormonal activities of extracted dust in five cell-based luciferase reporter assays and dust concentrations of 42 measured PEAS, OPEs, and PBDEs, transformed as either raw or potency-weighted concentrations based on Tox21 high-throughput screening data.RESULTS: All dust samples were hormonally active, showing antagonistic activity toward peroxisome proliferator-activated receptor (PPAR72) (100%; 46 of 46 samples), thyroid hormone receptor (TAP) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor (ER alpha) (96%; 44 samples); and binding competition with thyroxine (T-4) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as 4 jig of extracted dust. in regression models for each chemical class, interquartile range increases in potency-weighted or unknown-potency chemical concentrations were associated with higher hormonal activities of dust extracts (potency-weighted: Sigma PFAS-TR beta, up arrow 28%, p < 0.05; Sigma OPEs-TR beta, up arrow 27%, p = 0.08; Sigma PBDEs-TR beta, up arrow 20%, p < 0.05; Sigma PBDEs-ER alpha, up arrow 17.7%, p = 0.08; unknown-potency: Sigma OPEs-TTR, up arrow 34%, p < 0.05; Sigma OPEs-AR, up arrow 13%, p = 0.06), adjusted for chemicals with active, inactive, and unknown Tox21 designations.DISCUSSION: All indoor dust samples exhibited hormonal activities, which were associated with PFAS, PBDE, and OPE levels.Reporter gene cell-based assays are relatively inexpensive, health-relevant evaluations of toxic loads of chemical mixtures that building occupants are exposed to.