Tissue disposition, excretion and metabolism of 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) in the male Sprague-Dawley rat.
1. A disposition, metabolism and excretion study of orally administered 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) was conducted in the conventional and bile duct-cannulated male rat. 2. In the conventional rat, >50% of the radiolabelled dose was retained at 72 h, and lipophilic tissues were the preferred sites for disposition, i.e. adipose tissue, adrenals, gastrointestinal tract and skin. 3. Urinary excretion of BDE-99 was very low (<1% of dose), and glucuronidation of phenolic metabolites was suggested. 4. Biliary excretion of BDE-99 was slightly greater than observed in urine, i.e. 3.6% at 72 h. 5. Over 43% of the dose in the conventional male rat and 86% in the bile duct-cannulated rat was excreted in the faeces, mainly as the unmetabolized parent compound. 6. Metabolites in bile and faeces were not conjugated. Mono- and di-hydroxylated pentabromodiphenyl ether metabolites were characterized by mass spectrometry. Two thiol metabolites were characterized in the bile. Oxidative debromination was also observed in the faecal metabolites. 7. Tissue BDE-99 was readily extractable, except for in the liver. The tissue (14)C was not associated with lipids and was mainly the unmetabolized parent compound. 8. Total thyroxine (T4) plasma levels were elevated at 3 and 6 days, and returned to control levels by day 12.
Hakk
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USDA, ARS, Biosciences Research Laboratory, PO Box 5674, Fargo, ND 58105-5647, USA. hakkh@fargo.ars.usda.gov
Larsen
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G
Klasson-Wehler
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D000273:Adipose Tissue / Q000378:metabolism; D000284:Administration, Oral; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D002250:Carbon Radioisotopes; D004064:Digestive System / Q000378:metabolism; D005411:Flame Retardants / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D015394:Molecular Structure; D010647:Phenyl Ethers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D011075:Polybrominated Biphenyls; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism; D013974:Thyroxine / Q000097:blood; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; C086401:pentabromodiphenyl ether; D013974:Thyroxine