Chemical characterization and disposition studies with 1,2,7,8-tetrabromodibenzofuran in the rat.
Polybrominated dibenzo-p-dioxins and dibenzofurans have been identified as potential environmental contaminants. The present studies were designed to characterize the chemical disposition of a tetrabrominated dibenzofuran. The isomer-specific pattern of 1,2,7,8-tetrabromodibenzofuran (TBDF) was chemically characterized using high-pressure liquid chromatography, gas chromatography/mass spectrometry, infrared absorption, and proton nuclear magnetic resonance techniques. The absorption, distribution, and elimination of 1,2,7,8-[4,6-3H]-TBDF were examined in the rat following a single oral, dermal, or intravenous dose of 1 nmol/kg. The 1,2,7,8-TBDF was rapidly excreted in the bile (approximately 50% of the dose in 8 h). Likewise, over half of the administered dose was found in the feces and intestine contents 24 h after iv administration and in feces 72 h after oral administration. Thus, the half-life of 1,2,7,8-TBDF is approximately 1 d. Major tissue depots included the liver, adipose tissue, and skin. The decline in hepatic concentrations observed in the iv and bile studies occurred in conjunction with metabolic elimination as well as a slight accumulation in adipose tissue. Dermal absorption of 1,2,7,8-TBDF, quantified as the amount contained in tissues (excluding the skin site) and excreta at 72 h, was estimated to be 29% of the administered dose. Thus, the general disposition profile of 1,2,7,8-TBDF in the rat is similar to that of other polyhalogenated aromatic hydrocarbons. Due to its rapid elimination, which is consistent with its predicted susceptibility to metabolic elimination, acute exposure to 1,2,7,8-TBDF would not be expected to result in the degree of toxicity associated with other more persistent congeners.
Kedderis
L B
LB
Curriculum in Toxicology, University of North Carolina at Chapel Hill.
Jackson
J A
JA
Patterson
D G
DG
Grainger
J
J
Diliberto
J J
JJ
Birnbaum
L S
LS
D000042:Absorption; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013723:Teratogens / Q000737:chemistry* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D001572:Benzofurans; D013723:Teratogens; C085094:1,2,7,8-tetrabromodibenzofuran