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


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          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.


          We aimed to quantify the hormonal activities of 46 dust samples and identify chemicals driving the observed activities.


          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 ( PPAR γ 2 ) (100%; 46 of 46 samples), thyroid hormone receptor ( TR β ) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor ( ER α ) (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 μ 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: Σ PFAS TR β , 28 % , p < 0.05 ; Σ OPEs TR β , 27 % , p = 0.08 ; Σ PBDEs TR β , 20 % , p < 0.05 ; Σ PBDEs ER α , 7.7 % , p = 0.08 ; unknown-potency: Σ OPEs TTR , 34 % , p < 0.05 ; Σ OPEs AR , 13 % , p = 0.06 ), adjusted for chemicals with active, inactive, and unknown Tox21 designations.


          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

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          Most cited references91

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          Estimation of Average Concentration in the Presence of Nondetectable Values

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            A Review of the Pathways of Human Exposure to Poly- and Perfluoroalkyl Substances (PFASs) and Present Understanding of Health Effects

            Here we review present understanding of sources and trends in human exposure to poly- and perfluoroalkyl substances (PFASs) and epidemiologic evidence for impacts on cancer, immune function, metabolic outcomes, and neurodevelopment. More than 4000 PFASs have been manufactured by humans and hundreds have been detected in environmental samples. Direct exposures due to use in products can be quickly phased out by shifts in chemical production but exposures driven by PFAS accumulation in the ocean and marine food chains and contamination of groundwater persist over long timescales. Serum concentrations of legacy PFASs in humans are declining globally but total exposures to newer PFASs and precursor compounds have not been well characterized. Human exposures to legacy PFASs from seafood and drinking water are stable or increasing in many regions, suggesting observed declines reflect phase-outs in legacy PFAS use in consumer products. Many regions globally are continuing to discover PFAS contaminated sites from aqueous film forming foam (AFFF) use, particularly next to airports and military bases. Exposures from food packaging and indoor environments are uncertain due to a rapidly changing chemical landscape where legacy PFASs have been replaced by diverse precursors and custom molecules that are difficult to detect. Multiple studies find significant associations between PFAS exposure and adverse immune outcomes in children. Dyslipidemia is the strongest metabolic outcome associated with PFAS exposure. Evidence for cancer is limited to manufacturing locations with extremely high exposures and insufficient data are available to characterize impacts of PFAS exposures on neurodevelopment. Preliminary evidence suggests significant health effects associated with exposures to emerging PFASs. Lessons learned from legacy PFASs indicate that limited data should not be used as a justification to delay risk mitigation actions for replacement PFASs.
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              A Never-Ending Story of Per- and Polyfluoroalkyl Substances (PFASs)?

              More than 3000 per- and polyfluoroalkyl substances (PFASs) are, or have been, on the global market, yet most research and regulation continues to focus on a limited selection of rather well-known long-chain PFASs, particularly perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA) and their precursors. Continuing to overlook the vast majority of other PFASs is a major concern for society. We provide recommendations for how to proceed with research and cooperation to tackle the vast number of PFASs on the market and in the environment.

                Author and article information

                Environ Health Perspect
                Environ Health Perspect
                Environmental Health Perspectives
                Environmental Health Perspectives
                14 April 2021
                April 2021
                : 129
                : 4
                [ 1 ]Department of Environmental Health, Harvard T.H. Chan School of Public Health , Boston, Massachusetts, USA
                [ 2 ]Department of Population Health Sciences, Harvard Graduate School of Arts and Sciences , Cambridge, Massachusetts, USA
                [ 3 ]Department of Biology, University of Massachusetts Amherst , Amherst, Massachusetts, USA
                [ 4 ]BioDetection Systems , Amsterdam, Netherlands
                [ 5 ]Department of Pediatrics and Department of Environmental Medicine, New York University School of Medicine , New York, New York, USA
                Author notes
                Address correspondence to Anna S. Young, 401 Park Dr., 4W Suite 405, Boston, MA 02215 USA. Email: ayoung@ 123456mail.harvard.edu

                EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.


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