title: Comparative Metabolism Studies of Hexabromocyclododecane (HBCD) Diastereomers in Male Rats Following a Single Oral Dose.
abstract: Male Sprague-Dawley rats were dosed orally with 3 mg/kg of one of three hexabromocyclododecane (HBCD) diastereomers. Each diastereomer was well absorbed (73-83%), and distributed preferentially to lipophilic tissues. Feces were the major route of excretion; cumulatively accounting for 42% of dose for α-HBCD, 59% for ß-HBCD, and 53% for γ-HBCD. Urine was also an important route of HBCD excretion, accounting for 13% of dose for α-HBCD, 30% for ß-HBCD, and 21% for γ-HBCD. Total metabolism of HBCD diastereomers followed the rank order ß > γ > α, and was >65% of that administered. The metabolites formed were distinct in male rats: α-HBCD did not debrominate or stereoisomerize, but formed two hydroxylated metabolites; ß- and γ-HBCD were both extensively metabolized via pathways of stereoisomerization, oxidation, dehydrogenation, reductive debromination, and ring opening. ß-HBCD was biotransformed to two mercapturic acid pathway metabolites. The metabolites of ß- and γ-HBCD were largely distinct, and could possibly be used as markers of exposure. These isomer-specific data suggest that α-HBCD would be the most dominant HBCD diastereomer in biological tissues because it was metabolized to the lowest degree and also accumulated from the stereoisomerization of the β- and γ- diastereomers.
authors.affiliation: USDA Agriculture Research Service, 1605 Albrecht Blvd Biosciences Research Laboratory, Fargo, North Dakota 58102-2765, United States.
authors.forename: Heldur
authors.initials: H
authors.lastname: Hakk
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: D006842:Hydrocarbons, Brominated; C089796:hexabromocyclododecane