Assessing Indoor Dust Interference with Human Nuclear Hormone Receptors in Cell-Based Luciferase Reporter Assays

By Young, Anna S., Thomas Zoeller, Russ Hauser, Tamarra James-Todd, Brent A. Coull, Peter A. Behnisch, Abraham Brouwer, Hongkai Zhu, Kurunthachalam Kannan, and Joseph G. Allen
Environ Health Perspect
April 19, 2021
DOI: 10.1289/EHP8054

Background: Per- and polyfluoroalkyl substances (PFAS), 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 PFAS, 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 (PPARγ2PPARγ2) (100%; 46 of 46 samples), thyroid hormone receptor (TRβTRβ) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor (ERαERα) (96%; 44 samples); and binding competition with thyroxine (T4T4) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as 4μg4μg 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: ΣPFAS−TRβΣPFAS-TRβ, ↑28%↑28%, p<0.05p<0.05; ΣOPEs−TRβΣOPEs-TRβ, ↑27%↑27%, p=0.08p=0.08; ΣPBDEs−TRβΣPBDEs-TRβ, ↑20%↑20%, p<0.05p<0.05; ΣPBDEs−ERαΣPBDEs-ERα, ↑7.7%↑7.7%, p=0.08p=0.08; unknown-potency: ΣOPEs−TTRΣOPEs-TTR, ↑34%↑34%, p<0.05p<0.05; ΣOPEs−ARΣOPEs-AR, ↑13%↑13%, p=0.06p=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.

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