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

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.

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.

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.

All dust samples were hormonally active, showing antagonistic activity toward peroxisome proliferator-activated receptor (PPARγ2PPARγ2<math><mrow><mtext>PPAR</mtext><mi>γ</mi><mn>2</mn></mrow></math>) (100%; 46 of 46 samples), thyroid hormone receptor (TRβTRβ<math><mrow><mtext>TR</mtext><mi>β</mi></mrow></math>) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor (ERαERα<math><mrow><mtext>ER</mtext><mi>α</mi></mrow></math>) (96%; 44 samples); and binding competition with thyroxine (T4T4<math><mrow><msub><mrow><mi>T</mi></mrow><mrow><mn>4</mn></mrow></msub></mrow></math>) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as 4μg4μg<math><mrow><mn>4</mn><mspace></mspace><mi>μ</mi><mi>g</mi></mrow></math> 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<math><mrow><mi>Σ</mi><mtext>PFAS</mtext><mo>-</mo><mtext>TR</mtext><mi>β</mi></mrow></math>, ↑28%↑28%<math><mrow><mo>↑</mo><mn>28</mn><mo>%</mo></mrow></math>, p<0.05p<0.05<math><mrow><mi>p</mi><mo><</mo><mn>0.05</mn></mrow></math>; ΣOPEs−TRβΣOPEs-TRβ<math><mrow><mi>Σ</mi><mtext>OPEs</mtext><mo>-</mo><mtext>TR</mtext><mi>β</mi></mrow></math>, ↑27%↑27%<math><mrow><mo>↑</mo><mn>27</mn><mo>%</mo></mrow></math>, p=0.08p=0.08<math><mrow><mi>p</mi><mo>=</mo><mn>0.08</mn></mrow></math>; ΣPBDEs−TRβΣPBDEs-TRβ<math><mrow><mi>Σ</mi><mtext>PBDEs</mtext><mo>-</mo><mtext>TR</mtext><mi>β</mi></mrow></math>, ↑20%↑20%<math><mrow><mo>↑</mo><mn>20</mn><mo>%</mo></mrow></math>, p<0.05p<0.05<math><mrow><mi>p</mi><mo><</mo><mn>0.05</mn></mrow></math>; ΣPBDEs−ERαΣPBDEs-ERα<math><mrow><mi>Σ</mi><mtext>PBDEs</mtext><mo>-</mo><mtext>ER</mtext><mi>α</mi></mrow></math>, ↑7.7%↑7.7%<math><mrow><mo>↑</mo><mn>7.7</mn><mo>%</mo></mrow></math>, p=0.08p=0.08<math><mrow><mi>p</mi><mo>=</mo><mn>0.08</mn></mrow></math>; unknown-potency: ΣOPEs−TTRΣOPEs-TTR<math><mrow><mi>Σ</mi><mtext>OPEs</mtext><mo>-</mo><mtext>TTR</mtext></mrow></math>, ↑34%↑34%<math><mrow><mo>↑</mo><mn>34</mn><mo>%</mo></mrow></math>, p<0.05p<0.05<math><mrow><mi>p</mi><mo><</mo><mn>0.05</mn></mrow></math>; ΣOPEs−ARΣOPEs-AR<math><mrow><mi>Σ</mi><mtext>OPEs</mtext><mo>-</mo><mtext>AR</mtext></mrow></math>, ↑13%↑13%<math><mrow><mo>↑</mo><mn>13</mn><mo>%</mo></mrow></math>, p=0.06p=0.06<math><mrow><mi>p</mi><mo>=</mo><mn>0.06</mn></mrow></math>), adjusted for chemicals with active, inactive, and unknown Tox21 designations.