The fate of β-hexabromocyclododecane in female C57BL/6 mice

Abstract

1,2,5,6,9,10-Hexabromocyclododecane (HBCD) is a high production volume cycloaliphatic used as an additive flame retardant primarily in polystyrene foam building materials. HBCD mixtures contain three major stereoisomers, alpha (α), beta (β), and gamma (γ), at a typical ratio of 1.2:0.6:8.2. The toxicokinetic properties of the α and γ isomers differ. For instance, α-HBCD has greater bioavailability and potential for accumulation in mice than γ-HBCD. The present study reports comparative kinetics data for β-HBCD needed to support toxicological evaluations of HBCD mixtures. Results indicated that a single oral dose of 3mg/kg of [(14)C]-labeled β-HBCD was absorbed rapidly (≥ 85% total dose) in the female C57BL/6 mouse. The C max for β-HBCD-derived radioactivity in tissues, except adipose, was observed 3h following gavage. Approximately 90% of the administered dose was excreted in urine and feces within 24h, primarily as β-HBCD-derived metabolites. A portion of the dose (circa 9%) was excreted in feces as γ-HBCD. Oral administration of 30 or 100mg/kg of β-HBCD resulted initially in slower rates of [(14)C] elimination; however, cumulative excretion data were similar across the dosing range 4 days postdosing. Residual concentrations of [(14)C] in tissues were highest in adipose and liver. β-HBCD-derived radioactivity accumulated in most tissues following four consecutive daily oral doses of 3mg/kg. The extent of metabolism and excretion of β-HBCD in female C57BL/6 mice was similar to that for γ-HBCD. The potential for accumulation of β-HBCD-derived material in most tissues appeared to be less than for α-HBCD.