Research Articles Advance Publication
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
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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.
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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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