The Metabolism of 4-Chlorobiphenyl in the Pig

Safe, S.; Ruzo, Luis O.; Jones, D. Gareth; Platonow, N; Hutzinger, O.

doi:10.1139/y75-056

Cited by 18 publications

(9 citation statements)

References 9 publications

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“…40,42,43 These studies have reported that 4′OH-PCB3 > 3′4′-diOH-PCB3 > 3′OH-PCB3 are three major phenolic metabolites in naïve animals. Rats induced with phenobarbital (PB) and 3-methylcholanthrene (3-MC) exhibited enhanced metabolism of PCBs, suggesting a role for hepatic CYP1A and 2B isoforms in the formation of phenolic metabolites.…”

Section: Discussionmentioning

confidence: 99%

Disposition of Phenolic and Sulfated Metabolites after Inhalation Exposure to 4-Chlorobiphenyl (PCB3) in Female Rats

Dhakal

Uwimana

Adamcakova‐Dodd

et al. 2014

Chem. Res. Toxicol.

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PCBs, such as PCB3, are air contaminants in buildings and outdoors. Metabolites of PCB3 are potential endocrine disrupting chemicals and genotoxic agents. We studied the disposition of phenolic and sulfated metabolites after acute nose-only inhalation exposure to airborne PCB3 for 2 h in female rats. Inhalation exposure was carried out in three groups. In the first group, rats exposed to an estimated dose of 26 μg/rat were euthanized at 0, 1, 2, and 4 h after exposure. Highest concentrations of phenols and sulfates were observed at 0 h, and the values were 7 ± 1 and 560 ± 60 ng/mL in serum, 213 ± 120 and 842 ± 80 ng/g in liver, 31 ± 27 and 22 ± 7 ng/g in lung, and 27 ± 6 and 3 ± 0 ng/g in brain, respectively. First-order serum clearance half-lives of 0.5 h for phenols and 1 h for sulfates were estimated. In the second group, rats exposed to an estimated dose of 35 μg/rat were transferred to metabolism cages immediately after exposure for the collection of urine and feces over 24 h. Approximately 45 ± 5% of the dose was recovered from urine and consisted mostly of sulfates; the 18 ± 5% of the dose recovered from feces was exclusively phenols. Unchanged PCB3 was detected in both urine and feces but accounted for only 5 ± 3% of the dose. Peak excretion of metabolites in both urine and feces occurred within 18 h postexposure. In the third group, three bile-cannulated rats exposed to an estimated dose of 277 μg/rat were used for bile collection. Bile was collected for 4 h immediately after 2 h exposure. Biliary metabolites consisted mostly of sulfates, some glucuronides, and lower amounts of the free phenols. Control rats in each group were exposed to clean air. Clinical serum chemistry values, serum T4 level, and urinary 8-hydroxy-2′-deoxyguanosine were similar in treated and control rats. These data show that PCB3 is rapidly metabolized to phenols and conjugated to sulfates after inhalation and that both of these metabolites are distributed to liver, lungs, and brain. The sulfates elaborated into bile are either reabsorbed or hydrolyzed in the intestine and excreted in the feces as phenols.

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Section: Discussionmentioning

confidence: 99%

Disposition of Phenolic and Sulfated Metabolites after Inhalation Exposure to 4-Chlorobiphenyl (PCB3) in Female Rats

Dhakal

Uwimana

Adamcakova‐Dodd

et al. 2014

Chem. Res. Toxicol.

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“…Evidence for the formation of arene oxide intermediates in PCB metabolism was first provided by Gardner et al (103) in their study of the metabolism of 2,5,2',5'-tetrachlorobiphenyl and in a later study of 4-chlorobiphenyl metabolism by Safe et al (96), which was specifically designed to provide evidence of an arene oxide intermediate. Metabolism of PCBs which do not have two adjacent unsubstituted carbon atoms by hepatic mixed-function oxidases, via direct hydroxylation of the biphenyl molecule and/or the formation of an arene oxide between a chlorinated and an unsubstituted carbon atom could occur, but each of these mechanisms would be expected to be slower than arene oxide formation between two unsubstituted carbon atoms (104,105).…”

Section: Metabolism Of Individual Pcbsmentioning

confidence: 99%

Metabolism and biochemical toxicity of PCBs and PBBs

Matthews¹,

Fries²,

Gardner³

et al. 1978

Environ Health Perspect

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“…Environmental Health Perspectives (43), especially in cases where vicinal (1,2 or adjacent) unsubstituted carbons are found in the molecule (44). The corresponding dihydrodiol and/or catechol generally occur along with the phenolic metabolites.…”

Section: Nonmetabolic Alteration Of Chlorinated Biphenylsmentioning

confidence: 99%