Journal article
Identification of Sulfated Metabolites of 4-Chlorobiphenyl (PCB3) in the Serum and Urine of Male Rats
Chemical research in toxicology, Vol.25(12), pp.2796-2804
12/17/2012
DOI: 10.1021/tx300416v
PMCID: PMC3524396
PMID: 23137097
Abstract
Polychlorinated biphenyls (PCBs) are legacy pollutants that exert toxicities through various mechanisms. In the recent years exposure to PCBs via inhalation has been recognized as a hazard. Those PCBs with lower numbers of chlorine atoms (LC-PCBs) are semi-volatile, and have been reported in the urban air, as well as in the indoor air of older buildings. LC-PCBs are bioactivated to phenols and further to quinone electrophiles with genotoxic/carcinogenic potential. We hypothesized that phenolic LC-PCBs are subject to conjugation and excretion in the urine. PCB3, often present in high concentrations in air, is a prototypical congener for the study of the metabolism and toxicity of LC-PCBs. Our objective was to identify metabolites of PCB3 in urine that could be potentially employed in the estimation of exposure to LC-PCBs. Male Sprague Dawley rats (150–175 g) were housed in metabolism cages and received a single intraperitoneal injection of 600 µmol/kg body weight of PCB3. Urine was collected every four hours; rats were euthanized at 36 h and serum was collected. LC-MS analysis of urine before and after incubation with β-glucuronidase and sulfatase showed that sulfate conjugates were in higher concentrations than glucuronide conjugates and free phenolic forms. At least two major metabolites, and two minor metabolites were identified in urine that could be attributed to mercapturic acid metabolites of PCB3. Quantitation by authentic standards confirmed that approximately 3% of the dose was excreted in the urine as sulfates over 36 hours; with peak excretion occurring at 10–20 h after exposure. The major metabolites were 4’PCB3 sulfate, 3’PCB3 sulfate, 2’PCB3 sulfate, and presumably a catechol sulfate. The serum concentration of 4’PCB3 sulfate was 6.18±2.16 µg/mL. This is the first report that sulfated metabolites of PCBs are formed
in vivo
. These findings suggest a prospective approach for exposure assessment of LC- PCBs by analysis of phase II metabolites in urine.
Details
- Title: Subtitle
- Identification of Sulfated Metabolites of 4-Chlorobiphenyl (PCB3) in the Serum and Urine of Male Rats
- Creators
- Kiran Dhakal - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of IowaXianran He - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of IowaHans-Joachim Lehmler - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of IowaLynn M Teesch - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of IowaMichael W Duffel - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of IowaLarry W Robertson - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa
- Resource Type
- Journal article
- Publication Details
- Chemical research in toxicology, Vol.25(12), pp.2796-2804
- DOI
- 10.1021/tx300416v
- PMID
- 23137097
- PMCID
- PMC3524396
- NLM abbreviation
- Chem Res Toxicol
- ISSN
- 0893-228X
- eISSN
- 1520-5010
- Grant note
- P42 ES013661 || ES / National Institute of Environmental Health Sciences : NIEHS
- Language
- English
- Date published
- 12/17/2012
- Academic Unit
- Occupational and Environmental Health; Core Research Facilities; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Iowa Superfund Research Program; Medicine Administration; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984001083302771
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