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Environ Health Perspect; DOI:10.1289/EHP242

Serum Metabolomic Profiles in Neonatal Mice following Oral Brominated Flame Retardant Exposures to Hexabromocyclododecane (HBCD) Alpha, Gamma, and Commercial Mixture

David T. Szabo,1,2 Wimal Pathmasiri,3 Susan Sumner,3 and Linda S. Birnbaum4
Author Affiliations open
1US Environmental Protection Agency, National Human Environmental Exposure Research Laboratory, Research Triangle Park, North Carolina, USA; 2Curriculum in Toxicology, University of North Carolina – Chapel Hill, Chapel Hill, North Carolina, USA; 3Discovery Sciences, Research Triangle Institute International, Research Triangle Park, North Carolina, USA; 4National Institute of Environmental Health Sciences and National Toxicology Program, Research Triangle Park, North Carolina, USA

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  • Background: Hexabromocyclododecane (HBCD) is a high production volume brominated flame retardant added to building insulation foams, electronics, and textiles. HBCD is a commercial-mixture (CM-HBCD) composed of 3 main stereoisomers: α-HBCD (10%); β-HBCD (10%); γ-HBCD (80%). A shift from the dominant stereoisomer γ-HBCD to α-HBCD is detected in humans and wildlife.

    Objectives: Considering CM-HBCD has been implicated in neurodevelopment and endocrine disruption, with expected metabolism perturbations, metabolomics was performed on mice serum obtained during a window-of-developmental neurotoxicity to draw correlations between early-life exposures, developmental outcomes, and predict health risks.

    Methods: Ten postnatal day (PND) female C57BL/6 mice were administered a single gavage dose of α-, γ-, or CM-HBCD at 3, 10, and 30 mg/kg. NMR metabolomics was used to analyze 60 µL serum aliquots of blood collected 4 days post-oral exposure.

    Results: Infantile mice exposed to α-, γ-, or CM-HBCD demonstrated differences in endogenous metabolites by treatment- and dose-groups, including metabolites involved in glycolysis, gluconeogenesis, lipid metabolism, citric acid cycle, and neurodevelopment. Ketone bodies, 3-hydroxybutyrate and acetoacetate, were non-statistically elevated, compared to mean control levels, in all treatment- and dose-groups while glucose, pyruvate, and alanine varied. Acetoacetate was significantly increased in the 10 mg/kg α-HBCD, and was non-significantly decreased with CM-HBCD. A third ketone body, acetone, was significantly lower in the 30 mg/kg α-HBCD group with significant increases in pyruvate at the same treatment- and dose group. Metabolites significant in differentiating treatment- and dose-groups were also identified, including decreases in amino acids glutamate (excitatory neurotransmitter in learning and memory) and phenylalanine (neurotransmitter precursor) after α-HBCD and γ-HBCD exposure, respectively.

    Conclusions: We demonstrate that four days following a single neonatal oral exposure to α-, γ-, and CM-HBCD results in different serum metabolomic profiles, indicating stereoisomer- and mixture-specific effects and possible mechanisms of action.

  • This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process.

    Citation: Szabo DT, Pathmasiri W, Sumner S, Birnbaum LS. Serum Metabolomic Profiles in Neonatal Mice following Oral Brominated Flame Retardant Exposures to Hexabromocyclododecane (HBCD) Alpha, Gamma, and Commercial Mixture. Environ Health Perspect; http://dx.doi.org/10.1289/EHP242

    Received: 1 October 2015
    Revised: 30 December 2015
    Accepted: 19 September 2016
    Published: 4 November 2016

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