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Extraction Analysis House Flame Retardants: Page 1 ofEnvironmental 28 Science & Technology Dust • PBDEs • BFRs • PFRs
T3
TRβ LBD
GAL4Plus Environment ACS Paragon DBD
HEK CELL
GAL4
REPORTER
Environmental Science & Technology
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RESEARCH ARTICLE
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Chemical mixtures isolated from house dust disrupt thyroid receptor β (TRβ) signaling
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Erin M. Kollitz†, Christopher D. Kassotis†, Kate Hoffman†, P. Lee Ferguson†, Julie Ann Sosa‡, Heather M. Stapleton†* †
Nicholas School of the Environment, Duke University, Box 90328, Durham, North Carolina 27708, United States ‡ Department of Surgery, University of California at San Francisco, 513 Parnassus Avenue, San Francisco, California 94117, United States
*Corresponding Author Information: Phone: (919) 613-8717 E-mail:
[email protected] ORCID # Erin M. Kollitz ........................... 0000-0003-1769-1496 Christopher D. Kassotis ............. 0000-0002-0990-2428 Kate Hoffman............................. 0000-0001-8029-7710 P. Lee Ferguson ......................... 0000-0002-8367-7521 Julie Ann Sosa............................ 0000-0002-3356-7316 Heather M. Stapleton ................. 0000-0002-9995-6517
Author Disclosure: JAS is a member of the Data Monitoring Committee of the Medullary Thyroid Cancer Consortium Registry supported by Novo Nordisk, GlaxoSmithKline, Astra Zeneca, and Eli Lilly. EMK, CDK, KH, PLF, and HMS have nothing to disclose.
ACS Paragon Plus Environment
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Environmental Science & Technology
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Abstract:
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House dust is a source of exposure to chemicals that can impact hormone regulation. This study was
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designed to evaluate the potential of house dust mixtures (n=137) to disrupt thyroid hormone nuclear
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receptor signaling in a cell-based reporter assay and examine associations with thyroid hormones (TH)
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measured in residents of the homes. Approximately 41% of the extracts (ranging from 10.5 -4.097 µg of
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dust/mL) significantly antagonized TRβ signaling by 20-67% relative to the hormone control. The
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concentrations of twelve flame retardants (FRs) quantified in the mixtures were significantly correlated
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with TRβ antagonism; however, they were inactive when tested individually. We hypothesize that the
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observed antagonism is due to mixture effects or unidentified compounds that co-occur with FRs. Dust
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extract potency was significantly associated with free thyroxine (FT4, rs = -0.64, p20% relative to the T3 control.
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The remaining 80 extracts (58.4%) did not affect TRβ signaling and were considered inactive (see Figure
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1 for representative examples of active and inactive extracts). The dust concentrations tested in this study
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varied based on the mass of dust collected in all the homes. While the dust concentration ranges in the
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active and inactive extracts were similar, the median dust concentration in active extracts was over 2-fold
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higher than the median concentration in inactive extracts (Table 1). TRβ antagonism was significantly and
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positively associated with the dust mass concentration in the well (Figure 2; rs = 0.54, p 15% viability loss) were included in the
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analysis.
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Flame retardant correlations. To gain a better understanding of the chemicals potentially driving the
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observed response, we assessed the relationship between the final concentration in the wells of the twelve
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flame retardants in the dust mixtures and the degree of TRβ antagonism. Summary statistics of the FR
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concentrations are presented in Table 1, and the Spearman correlation results are presented in Table 2.
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Antagonism was significantly and positively associated with the concentrations of all 12 flame retardants
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in the mixtures (Table 2, rs = 0.25 – 0.44). The strongest correlations were observed with BDE-209 (rs =
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0.44, p
