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

Details

• Personal Author:
  Allen JG ; Behnisch PA ; Brouwer A ; Coull BA ; Hauser R ; James-Todd T ; Kannan K ; Young AS ; Zhu H ; Zoeller T
• Description:
  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 (PPARgamma2) (100%; 46 of 46 samples), thyroid hormone receptor (TRbeta) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor (ERalpha) (96%; 44 samples); and binding competition with thyroxine (T4) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as 4 microg 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: SigmaPFAS-TRbeta, (up arrow) 28%, p< 0:05; SigmaROPEs-TRbeta, (up arrow) 27%, p= 0:08; SigmaPBDEs-TRbeta, (up arrow) 20%, p< 0:05; SigmaPBDEs-ERalpha (up arrow) 7:7%, p= 0:08; unknown-potency: SigmaOPEs-TTR, (up arrow) 34%, p< 0:05; SigmaOPEs-AR, (up arrow) 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. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Biological Assay Cells, Cultured Dust Endocrine System Esters Genetics Occupational Health Safety
• Keywords:
  Airborne Dusts Bioassays Cell Cultures Genes Hormone Activity Hormones Indoor Environments Per- And Polyfluoroalkyl Substances PFAS Polybrominated Diphenyl Ethers
• ISSN:
  0091-6765
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; New York ; OSHA Region 1 ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  129
• Issue:
  4
• NIOSHTIC Number:
  nn:20062603
• Citation:
  Environ Health Perspect 2021 Apr; 129(4):047010
• Contact Point Address:
  Anna S. Young, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 401 Park Dr., 4 W Suite 405, Boston, MA 02215, USA
• Email:
  ayoung@mail.harvard.edu
• CAS Registry Number:
  Perfluorocarbons (CAS RN 308069-13-8)
• Federal Fiscal Year:
  2021
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Environmental Health Perspectives
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4a2e04ad3b3f8ed066142affc5ee0c5e3575f923e436ab510615d86565445fe26e91b8b8c606e4313caa9c20c17eb26da7c168704fb226808e96f76e73eab377
• Download URL:
  https://stacks.cdc.gov/view/cdc/225811/cdc_225811_DS1.pdf
• File Type:
  [PDF - 226.17 KB ]