Journal article
Disposition of phenolic and sulfated metabolites after inhalation exposure to 4-chlorobiphenyl (PCB3) in female rats
Chemical research in toxicology, Vol.27(8), pp.1411-1420
08/18/2014
DOI: 10.1021/tx500150h
PMCID: PMC4137987
PMID: 24988477
Abstract
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.
Details
- Title: Subtitle
- Disposition of phenolic and sulfated metabolites after inhalation exposure to 4-chlorobiphenyl (PCB3) in female rats
- Creators
- Kiran Dhakal - Interdisciplinary Graduate Program in Human Toxicology and ‡Department of Occupational and Environmental Health, The University of Iowa , Iowa City, Iowa 52242-5000, United StatesEric UwimanaAndrea Adamcakova-DoddPeter S ThorneHans-Joachim LehmlerLarry W Robertson
- Resource Type
- Journal article
- Publication Details
- Chemical research in toxicology, Vol.27(8), pp.1411-1420
- DOI
- 10.1021/tx500150h
- PMID
- 24988477
- PMCID
- PMC4137987
- NLM abbreviation
- Chem Res Toxicol
- ISSN
- 0893-228X
- eISSN
- 1520-5010
- Publisher
- United States
- Grant note
- F32 DA026265 / NIDA NIH HHS P30 ES005605 / NIEHS NIH HHS P42 ES013661 / NIEHS NIH HHS P30 DK054759 / NIDDK NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 08/18/2014
- Academic Unit
- Civil and Environmental Engineering; Occupational and Environmental Health; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Iowa Superfund Research Program
- Record Identifier
- 9983997317002771
Metrics
29 Record Views