title: Hexabromonaphthalene contaminants of polybrominated biphenyls: chemical composition and disposition in the rat.
abstract: Hexabromonaphthalene (HBN) has been identified as a toxic contaminant of Firemaster BP-6, a mixture of polybrominated biphenyls (PBBs) that is used commercially as a fire retardant and that was responsible for a major public health emergency in Michigan in 1974. Previously reported to be a single compound, the hexabrominated naphthalene derived from direct bromination of naphthalene was here shown by high-field nuclear magnetic resonance (NMR) to be a mixture of two closely related isomers, 1,2,3,4,6,7-HBN and 2,3,4,5,6,7-HBN, in a ratio of 60:40. The absorption, distribution, metabolism, and excretion of the HBN mixture was studied in the male Fischer-344 rat. [14C] HBN was incompletely absorbed after oral doses of 0.4 and 4.0 mumol/kg body weight. After iv treatment, fecal excretion accounted for 24% of the total dose by the end of d 1, 44% by d 3, and 62% by d 35. Urinary excretion was negligible. The excreted radioactivity was in the form of metabolite(s). Biliary excretion studies confirmed the nature of the excreted dose. The tissue distribution pattern showed accumulation and redistribution during early time points (0.5-3 h). By the end of the first day, 30.7% and 12.3% of the total dose remained in the liver and fat, respectively. All other tissues accounted for less than 5% of the total dose by d 1. The major tissue depots remained liver and adipose tissue, which contained 26% and 4.6% of the total dose, respectively, by d 35. This residual radioactivity was found to be unmetabolized HBN. Thus, over 60% of the dose of HBN is readily metabolized and excreted and was tentatively identified with the toxic isomer 1,2,3,4,6,7-HBN. The remainder, probably 2,3,4,5,6,7-HBN, was relatively nontoxic and extremely persistent, with the liver being the primary site of long-term accumulation.
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D002250:Carbon Radioisotopes; D004340:Drug Contamination; D005243:Feces / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D006842:Hydrocarbons, Brominated; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009281:Naphthalenes; D011075:Polybrominated Biphenyls / Q000032:analysis* / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
chemical_list: C039699:2,3,4,5,6,7-hexabromonaphthalene; D002250:Carbon Radioisotopes; D006842:Hydrocarbons, Brominated; D009281:Naphthalenes; D011075:Polybrominated Biphenyls; C039698:1,2,3,4,6,7-hexabromonaphthalene