Identification of a sulfate metabolite of PCB 11 in human serum.
Despite increasing evidence for a major role for sulfation in the metabolism of lower-chlorinated polychlorinated biphenyls in vitro and in vivo, and initial evidence for potential bioactivities of the resulting sulfate ester metabolites, the formation of PCB sulfates in PCB exposed human populations had not been explored. The primary goal of this study was to determine if PCB sulfates, and potentially other conjugated PCB derivatives, are relevant classes of PCB metabolites in the serum of humans with known exposures to PCBs. In order to detect and quantify dichlorinated PCB sulfates in serum samples of 46 PCB-exposed individuals from either rural or urban communities, we developed a high-resolution mass spectrometry-based protocol using 4-PCB 11 sulfate as a model compound. The method also allowed the preliminary analysis of these 46 human serum extracts for the presence of other metabolites, such as glucuronic acid conjugates and hydroxylated PCBs. Sulfate ester metabolites derived from dichlorinated PCBs were detectable and quantifiable in more than 20% of analyzed serum samples. Moreover, we were able to utilize this method to detect PCB glucuronides and hydroxylated PCBs, albeit at lower frequencies than PCB sulfates. Altogether, our results provide initial evidence for the presence of PCB sulfates in human serum. Considering the inability of previously employed analytical protocols for PCBs to extract these sulfate ester metabolites and the concentrations of these metabolites observed in our current study, our data support the hypothesis that total serum levels of PCB metabolites in exposed individuals may have been underestimated in the past.
Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA, USA.
Fabian A
FA
Grimm
Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA; Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, USA.
Hans-Joachim
HJ
Lehmler
Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA; Department of Civil and Environmental Engineering, College of Engineering, The University of Iowa, Iowa City, USA.
Wen Xin
WX
Koh
Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, USA.
Jeanne
J
DeWall
High Resolution Mass Spectrometry Facility, The University of Iowa, Iowa City, USA.
Lynn M
LM
Teesch
Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA; Department of Civil and Environmental Engineering, College of Engineering, The University of Iowa, Iowa City, USA.
Keri C
KC
Hornbuckle
Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA; Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, USA.
Peter S
PS
Thorne
Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA; Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, USA.
Larry W
LW
Robertson
Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA, USA. Electronic address: michael-duffel@uiowa.edu.
Michael W
MW
Duffel
D005260:Female; D020723:Glucuronic Acid / Q000378:metabolism*; D054879:Halogenation; D006801:Humans; D006900:Hydroxylation; D013058:Mass Spectrometry; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000378:metabolism*; D044967:Serum; D013431:Sulfates / Q000378:metabolism*
D013431:Sulfates; C029906:3,3'-dichlorobiphenyl; D020723:Glucuronic Acid; D011078:Polychlorinated Biphenyls
Exposure assessment; Metabolism; PCB; Polychlorinated biphenyls; Sulfation