Pharmacokinetics of two major hydroxylated polychlorinated biphenyl metabolites with specific retention in rat blood.
1. Hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) are, depending on their structure, strongly retained in mammalian, fish and bird blood. This is due to strong, though reversible, binding to the thyroxine binding and transporting protein transthyretin. 2,3,3',4',5-Pentachloro-4-biphenylol (4-OH-CB 107) and 2,2',3,4',5,5',6-heptachloro-4-biphenylol (4-OH-CB 187) are two of five major OH-PCB congeners in human plasma. 2. The relative amounts of OH-PCB congeners vary between species and also between human populations, in spite of similar PCB congener patterns, and may depend on different pharmacokinetic parameters of the OH-PCBs. In the present study, the pharmacokinetic parameters of 4-OH-CB 107 and 4-OH-CB 187 were determined in the rat after a single intravenous dose of 1 micromol kg(-1). Plasma samples were analysed by gas chromatography/mass spectrometry. 3. 4-OH-CB 107 had a half-life of 3.8 days; 4-OH-CB 187 had a half-life of 15 days. Volumes of distribution were 0.07 and 0.11 l kg(-1), respectively; clearances (ml h(-1)) were 0.67 and 0.22, respectively; and the areas under the curve were estimated as approximately 1500 and 4450 nmol h ml(-1). 4. The pharmacokinetic parameters thus determined help to explain the observed differences in the relative amounts of OH-PCBs in humans and other mammals exposed to environmental PCBs.
Department of Environmental Chemistry, Stockholm University, SE-106 91 Stockholm, Sweden. tina.malmberg@mk.su.se
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T
Malmberg
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Hoogstraate
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A
Bergman
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Klasson Wehler
D000818:Animals; D006900:Hydroxylation; D008297:Male; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D011078:Polychlorinated Biphenyls / Q000097:blood* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D011078:Polychlorinated Biphenyls