TY  - JOUR
PY  - 2016//
TI  - Serum Metabolomic Profiles in Neonatal Mice following Oral Brominated Flame Retardant Exposures to Hexabromocyclododecane (HBCD) Alpha, Gamma, and Commercial Mixture
JO  - Environmental health perspectives
A1  - Szabo, David T.
A1  - Pathmasiri, Wimal
A1  - Sumner, Susan
A1  - Birnbaum, Linda S.
SP  - 651
EP  - 659
VL  - 125
IS  - 4
N2  - 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. <br><br>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. <br><br>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. <br><br>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. <br><br>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.<p />  <p>Language: en</p>
LA  - en
SN  - 0091-6765
UR  - http://dx.doi.org/10.1289/EHP242
ID  - ref1
ER  -