• Conference Proceeding

Metabolomic analysis of serum after treatment with the emerging pop flame retardant hexabromocyclododecane (HBCD): Commercial mixture, alpha and gamma stereoisomers elicit differential effects in infantile mice

Citation

Szabo, D. T., Pathmasiri, W., Diliberto, J. J., Sumner, S., & Birnbaum, L. S. (2011). Metabolomic analysis of serum after treatment with the emerging pop flame retardant hexabromocyclododecane (HBCD): Commercial mixture, alpha and gamma stereoisomers elicit differential effects in infantile mice. In [120], p. 482. .

Abstract

HBCD is an emerging persistent organic pollutant flame retardant added to foam
used in building insulation, electronics, and textiles. The commercial mixture is
composed of 3 stereoisomers: alpha (10%); beta (10%); gamma (80%). A shift
from the dominant gamma in the commercial mixture to alpha in humans and
biota is observed. To aid in predicting health risks of HBCD, metabolomic analysis
of serum was performed to improve our ability to draw correlations between early
life exposures and developmental outcomes. Metabolomics examines low molecular
weight endogenous compounds, and can give a snapshot of the physiological profile. Ten day old female C57BL/6 mice were exposed to a single gavage dose of corn oil vehicle, 3, or 30 mg/kg of the commercial HBCD mixture, alpha or gamma
HBCD. These concentrations of HBCDs induce effects at the molecular level in
infant pups. Serum was collected 4 days postexposure on postnatal day 14 (pnd
14). Samples were prepared for metabolomic analysis by mixing 60 ?L of pnd 14
trunk serum with saline, D2O, and formate as an internal control. 1H NMR spectra
were acquired using a 950 MHz NMR. Multivariate analysis was conducted for
NMR data processed by the traditional binning approach and via a concentration
library matching approach. Four days after oral exposure to a single dose, metabolic
profiles in serum could differentiate pups that received the vehicle, HBCD commercial mixture, alpha or gamma. Metabolites significant to the separation of dose groups were mapped to biochemical pathways finding significant metabolic perturbations in amino acid and energy metabolism. Metabolomics is a promising approach to determine biomarkers for examining the mechanistic link between low
levels of environmental exposure and disease/dysfunction. Abstract does not reflect
EPA or NCI/NIEHS policy.