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. We aimed to quantify the hormonal activities of 46 dust samples and identify chemicals drivin...
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Veröffentlicht in: | Environmental health perspectives 2021-04, Vol.129 (4), p.47010 |
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creator | Young, Anna S Zoeller, Thomas Hauser, Russ James-Todd, Tamarra Coull, Brent A Behnisch, Peter A Brouwer, Abraham Zhu, Hongkai Kannan, Kurunthachalam Allen, Joseph G |
description | 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 (
) (100%; 46 of 46 samples), thyroid hormone receptor (
) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor (
) (96%; 44 samples); and binding competition with thyroxine (
) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as
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:
,
,
;
,
,
;
,
,
;
,
,
; unknown-potency:
,
,
;
,
,
), 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. |
doi_str_mv | 10.1289/EHP8054 |
format | Article |
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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 (
) (100%; 46 of 46 samples), thyroid hormone receptor (
) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor (
) (96%; 44 samples); and binding competition with thyroxine (
) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as
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:
,
,
;
,
,
;
,
,
;
,
,
; unknown-potency:
,
,
;
,
,
), 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.</description><identifier>ISSN: 0091-6765</identifier><identifier>EISSN: 1552-9924</identifier><identifier>DOI: 10.1289/EHP8054</identifier><identifier>PMID: 33851871</identifier><language>eng</language><publisher>United States: National Institute of Environmental Health Sciences</publisher><subject>Air Pollution, Indoor - analysis ; Androgen receptors ; Assaying ; Building materials ; Chemicals ; Construction materials ; Diabetes ; Dust ; Environmental aspects ; Esters ; Estrogen receptors ; Estrogens ; Ethers ; Evaluation ; Flame Retardants - analysis ; Furniture ; Gene expression ; Halogenated Diphenyl Ethers - analysis ; Health aspects ; High-throughput screening ; Humans ; Indoor air quality ; Infertility ; Laboratories ; Luciferases ; Metabolism ; Nuclear receptors ; Organophosphates ; Perfluoroalkyl & polyfluoroalkyl substances ; Polybrominated diphenyl ethers ; Receptors ; Receptors, Cytoplasmic and Nuclear ; Regression analysis ; Regression models ; Renovation & restoration ; Reporter gene ; Thyroid ; Thyroid gland ; Thyroxine ; Transthyretin</subject><ispartof>Environmental health perspectives, 2021-04, Vol.129 (4), p.47010</ispartof><rights>COPYRIGHT 2021 National Institute of Environmental Health Sciences</rights><rights>Reproduced from Environmental Health Perspectives. This article is published under https://ehp.niehs.nih.gov/about-ehp/copyright-permissions (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c601t-f11a3a2da91a4e2c45ffe4d14c87eb16d600871d2e1e8422bbfa16cef1b175aa3</citedby><cites>FETCH-LOGICAL-c601t-f11a3a2da91a4e2c45ffe4d14c87eb16d600871d2e1e8422bbfa16cef1b175aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045486/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045486/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33851871$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Young, Anna S</creatorcontrib><creatorcontrib>Zoeller, Thomas</creatorcontrib><creatorcontrib>Hauser, Russ</creatorcontrib><creatorcontrib>James-Todd, Tamarra</creatorcontrib><creatorcontrib>Coull, Brent A</creatorcontrib><creatorcontrib>Behnisch, Peter A</creatorcontrib><creatorcontrib>Brouwer, Abraham</creatorcontrib><creatorcontrib>Zhu, Hongkai</creatorcontrib><creatorcontrib>Kannan, Kurunthachalam</creatorcontrib><creatorcontrib>Allen, Joseph G</creatorcontrib><title>Assessing Indoor Dust Interference with Human Nuclear Hormone Receptors in Cell-Based Luciferase Reporter Assays</title><title>Environmental health perspectives</title><addtitle>Environ Health Perspect</addtitle><description>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 (
) (100%; 46 of 46 samples), thyroid hormone receptor (
) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor (
) (96%; 44 samples); and binding competition with thyroxine (
) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as
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:
,
,
;
,
,
;
,
,
;
,
,
; unknown-potency:
,
,
;
,
,
), 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.</description><subject>Air Pollution, Indoor - analysis</subject><subject>Androgen receptors</subject><subject>Assaying</subject><subject>Building materials</subject><subject>Chemicals</subject><subject>Construction materials</subject><subject>Diabetes</subject><subject>Dust</subject><subject>Environmental aspects</subject><subject>Esters</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Ethers</subject><subject>Evaluation</subject><subject>Flame Retardants - analysis</subject><subject>Furniture</subject><subject>Gene expression</subject><subject>Halogenated Diphenyl Ethers - analysis</subject><subject>Health aspects</subject><subject>High-throughput screening</subject><subject>Humans</subject><subject>Indoor air quality</subject><subject>Infertility</subject><subject>Laboratories</subject><subject>Luciferases</subject><subject>Metabolism</subject><subject>Nuclear receptors</subject><subject>Organophosphates</subject><subject>Perfluoroalkyl & polyfluoroalkyl substances</subject><subject>Polybrominated diphenyl ethers</subject><subject>Receptors</subject><subject>Receptors, Cytoplasmic and Nuclear</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Renovation & restoration</subject><subject>Reporter gene</subject><subject>Thyroid</subject><subject>Thyroid gland</subject><subject>Thyroxine</subject><subject>Transthyretin</subject><issn>0091-6765</issn><issn>1552-9924</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkl-P1CAUxYnRuONq_AaGxETjQ1eglGlfTMZxdSaZuGb980oove2waaECVffbi9lx3SbzYHjgBn73AIeD0FNKzigrq9fnm08lKfg9tKBFwbKqYvw-WhBS0UwsRXGCHoVwRQihpRAP0UmelwUtl3SBxlUIEIKxHd7axjmP300hpjqCb8GD1YB_mrjHm2lQFn-cdA_K443zg7OAL0HDGJ0P2Fi8hr7P3qoADd5N2qT2VCdkdD6p4XSSug6P0YNW9QGeHOZT9PX9-Zf1JttdfNiuV7tMC0Jj1lKqcsUaVVHFgWletC3whnJdLqGmohGEpAc0DCiUnLG6bhUVGlpa02WhVH6K3tzojlM9QKPBRq96OXozKH8tnTJyvmPNXnbuhywJL3gpksDzg4B33ycIUV65ydt0Z8kE49WS0Ir_ozrVgzS2dUlMDyZouRKCClKJnCQqO0J1YJNFffKxNWl5xp8d4dNoYDD6aMOrWUNiIvyKnZpCkNvPl__PXnybsy_usHtQfdwH10_ROBvm4MsbUHsXgof21mlK5J-IykNEE_ns7sfccn8zmf8GOSjefQ</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Young, 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Indoor Dust Interference with Human Nuclear Hormone Receptors in Cell-Based Luciferase Reporter Assays</title><author>Young, Anna S ; Zoeller, Thomas ; Hauser, Russ ; James-Todd, Tamarra ; Coull, Brent A ; Behnisch, Peter A ; Brouwer, Abraham ; Zhu, Hongkai ; Kannan, Kurunthachalam ; Allen, Joseph G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c601t-f11a3a2da91a4e2c45ffe4d14c87eb16d600871d2e1e8422bbfa16cef1b175aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Air Pollution, Indoor - analysis</topic><topic>Androgen receptors</topic><topic>Assaying</topic><topic>Building materials</topic><topic>Chemicals</topic><topic>Construction materials</topic><topic>Diabetes</topic><topic>Dust</topic><topic>Environmental aspects</topic><topic>Esters</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Ethers</topic><topic>Evaluation</topic><topic>Flame Retardants - analysis</topic><topic>Furniture</topic><topic>Gene expression</topic><topic>Halogenated Diphenyl Ethers - analysis</topic><topic>Health aspects</topic><topic>High-throughput screening</topic><topic>Humans</topic><topic>Indoor air quality</topic><topic>Infertility</topic><topic>Laboratories</topic><topic>Luciferases</topic><topic>Metabolism</topic><topic>Nuclear receptors</topic><topic>Organophosphates</topic><topic>Perfluoroalkyl & polyfluoroalkyl substances</topic><topic>Polybrominated diphenyl ethers</topic><topic>Receptors</topic><topic>Receptors, Cytoplasmic and Nuclear</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>Renovation & restoration</topic><topic>Reporter gene</topic><topic>Thyroid</topic><topic>Thyroid gland</topic><topic>Thyroxine</topic><topic>Transthyretin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Young, Anna S</creatorcontrib><creatorcontrib>Zoeller, 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Young, Anna S</au><au>Zoeller, Thomas</au><au>Hauser, Russ</au><au>James-Todd, Tamarra</au><au>Coull, Brent A</au><au>Behnisch, Peter A</au><au>Brouwer, Abraham</au><au>Zhu, Hongkai</au><au>Kannan, Kurunthachalam</au><au>Allen, Joseph G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessing Indoor Dust Interference with Human Nuclear Hormone Receptors in Cell-Based Luciferase Reporter Assays</atitle><jtitle>Environmental health perspectives</jtitle><addtitle>Environ Health Perspect</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>129</volume><issue>4</issue><spage>47010</spage><pages>47010-</pages><issn>0091-6765</issn><eissn>1552-9924</eissn><abstract>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 (
) (100%; 46 of 46 samples), thyroid hormone receptor (
) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor (
) (96%; 44 samples); and binding competition with thyroxine (
) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as
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:
,
,
;
,
,
;
,
,
;
,
,
; unknown-potency:
,
,
;
,
,
), 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.</abstract><cop>United States</cop><pub>National Institute of Environmental Health Sciences</pub><pmid>33851871</pmid><doi>10.1289/EHP8054</doi><tpages>47010</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
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ispartof | Environmental health perspectives, 2021-04, Vol.129 (4), p.47010 |
issn | 0091-6765 1552-9924 |
language | eng |
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source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; JSTOR Archive Collection A-Z Listing; EZB-FREE-00999 freely available EZB journals; PubMed Central |
subjects | Air Pollution, Indoor - analysis Androgen receptors Assaying Building materials Chemicals Construction materials Diabetes Dust Environmental aspects Esters Estrogen receptors Estrogens Ethers Evaluation Flame Retardants - analysis Furniture Gene expression Halogenated Diphenyl Ethers - analysis Health aspects High-throughput screening Humans Indoor air quality Infertility Laboratories Luciferases Metabolism Nuclear receptors Organophosphates Perfluoroalkyl & polyfluoroalkyl substances Polybrominated diphenyl ethers Receptors Receptors, Cytoplasmic and Nuclear Regression analysis Regression models Renovation & restoration Reporter gene Thyroid Thyroid gland Thyroxine Transthyretin |
title | Assessing Indoor Dust Interference with Human Nuclear Hormone Receptors in Cell-Based Luciferase Reporter Assays |
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