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 ( $\text{PPAR}\mathrm{\gamma }2$ ) (100%; 46 of 46 samples), thyroid hormone receptor ( $\text{TR}\mathrm{\beta }$ ) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor ( $\text{ER}\mathrm{\alpha }$ ) (96%; 44 samples); and binding competition with thyroxine ( ${\mathrm{T}}_4$ ) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as $4\mathrm{\mu }\mathrm{g}$ 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: $\mathrm{\Sigma }\text{PFAS}–\text{TR}\mathrm{\beta }$ , $\uparrow 28\%$ , $p<0.05$ ; $\mathrm{\Sigma }\text{OPEs}–\text{TR}\mathrm{\beta }$ , $\uparrow 27\%$ , $p=0.08$ ; $\mathrm{\Sigma }\text{PBDEs}–\text{TR}\mathrm{\beta }$ , $\uparrow 20\%$ , $p<0.05$ ; $\mathrm{\Sigma }\text{PBDEs}–\text{ER}\mathrm{\alpha }$ , $\uparrow 7.7\%$ , $p=0.08$ ; unknown-potency: $\mathrm{\Sigma }\text{OPEs}–\text{TTR}$ , $\uparrow 34\%$ , $p<0.05$ ; $\mathrm{\Sigma }\text{OPEs}–\text{AR}$ , $\uparrow 13\%$ , $p=0.06$ ), 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