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Toxicokinetics of the Sterioisomer Specific Flame Retardant Hexabromocyclododecane (HBCD) Gamma: Effect of Dose, Time, and Repeated Exposure
Citation:
SZABO, D., J. J. DILIBERTO, J. HUWE, AND L. S. BIRNBAUM. Toxicokinetics of the Sterioisomer Specific Flame Retardant Hexabromocyclododecane (HBCD) Gamma: Effect of Dose, Time, and Repeated Exposure. Presented at 2009 Annual Society of Toxicology Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
This study examines the toxicokinetics of HBCD gamma in mice on the effects of dose, time, and repeated exposure.
Description:
Hexabromocyclododecanes (HBCDs) are high production volume brominated aliphatic cyclic hydrocarbons used as flame-retardants in foams, plastics and textiles. Commercial HBCD is a mixture of three main stereoisomers, alpha (α), beta (β) and gamma (γ). A shift from the high percentage of γ in the mixture and environment to a dominance of α in biota is observed. In predicting human health risk posed by HBCD, there’s a need to understand the disposition and elimination kinetics of the major commercial stereoisomer γ. Methods: Adult female C57BL/6 mice were gavaged with [C14] HBCD-γ (0.2uCi/mouse) at 10ml/kg and held in metabolism cages. Radioactivity in tissues and excreta were determined by combustion followed by liquid scintillation spectrometry. Metabolite profiles were examined using an Ultra Performance LC (UPLC) with a radiodetector. For the dose/response study, a single dose (3, 10, 30, or 100 mg/kg) was administered and mice held for 4 days. For the effect of time, mice were treated with a single 3mg/kg dose and held up to 14 days. For the repeated study, mice were dosed daily at 3mg/kg with non-radiolabed γ for 9 days followed by [C14] HBCD-γ on the 10th day and held for 4 days thereafter. Results: Tissue disposition is dose-independent and HBCD’s behavior appears to be linear across all doses measured including the repeated exposure. Tissue concentrations were highest in liver followed by blood and then fat. A large percentage of the administered dose is excreted in urine (23%) and feces (50%) by day 1. Preliminary results suggest none of the HBCD-derived radioactivity in the urine is parent chemical. Conclusions: HBCD-γ demonstrates a lack of tissue-specific sequestration. Considering measured levels in fat are lower than blood and liver, as well as the rapid elimination in both urine and feces, the biological persistence of HBCD-γ in mice appears limited. This finding may help explain the low levels of γ in biota. (This abstract does not reflect USEPA policy).