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

Abstract

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 ($\text{PPAR}\gamma 2$) (100%; 46 of 46 samples), thyroid hormone receptor ($\text{TR}\beta$) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor ($\text{ER}\alpha$) (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 $4\mu g$ 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: $\Sigma \text{PFAS}-\text{TR}\beta$, $\uparrow 28\%$, $p<0.05$; $\Sigma \text{OPEs}-\text{TR}\beta$, $\uparrow 27\%$, $p=0.08$; $\Sigma \text{PBDEs}-\text{TR}\beta$, $\uparrow 20\%$, $p<0.05$; $\Sigma \text{PBDEs}-\text{ER}\alpha$, $\uparrow 7.7\%$, $p=0.08$; unknown-potency: $\Sigma \text{OPEs}-\text{TTR}$, $\uparrow 34\%$, $p<0.05$; $\Sigma \text{OPEs}-\text{AR}$, $\uparrow 13\%$, $p=0.06$), 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. https://doi.org/10.1289/EHP8054.