Sulfate Conjugates Are Urinary Markers of Inhalation Exposure to 4-Chlorobiphenyl (PCB3)

Dhakal, Kiran; Adamcakova‐Dodd, Andrea; Lehmler, Hans‐Joachim; Thorne, Peter S.; Robertson, Larry W.

doi:10.1021/tx4001539

Cited by 31 publications

(61 citation statements)

References 22 publications

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“…Samples of human serum (1.0 ml each) were spiked with 40 ng of internal standard, 3-F,4′-PCB 3 sulfate, before they were acidified by the addition of one volume of 1% (v/v) formic acid and extracted with three additional volumes of acetonitrile (Dhakal et al 2013; Grimm et al 2015a). The samples were thoroughly mixed and incubated for 2 hours at 4°C, followed by 30 min centrifugation at 3000×g.…”

Section: Methodsmentioning

confidence: 99%

“…In vivo concentrations of sulfate conjugates were significantly higher than those of glutathione conjugate derivatives and glucuronide metabolites in serum of rats exposed to PCB 3 (Dhakal et al 2012). Considering the recent evidence for the metabolic conversion of OH-PCBs to PCB sulfates and potentially other conjugates in vivo , these metabolites have gained increasing scientific attention (Dhakal et al 2012; Dhakal et al 2013; Grimm et al 2015b). Moreover, the finding that PCB sulfates are competitive ligands for T 4 binding sites on the thyroid hormone binding protein transthyretin (TTR) in vitro indicates their bioactivity and potential toxicological relevance (Grimm et al 2013, 2015c).…”

Section: Introductionmentioning

confidence: 99%

“…Quantitative analytical procedures have not previously been developed for the detection of PCB sulfates in human serum, and concentrations of PCB sulfates in human populations have not been evaluated, despite their reported thyroid disrupting potential as well as their utility as biomarkers of PCB exposure in rats (Dhakal et al 2013; Dhakal et al 2014). …”

Section: Introductionmentioning

confidence: 99%

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Identification of a sulfate metabolite of PCB 11 in human serum

Grimm

Lehmler

Koh

et al. 2017

Environment International

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of a sulfate metabolite of PCB 11 in human serum

Grimm

Lehmler

Koh

et al. 2017

Environment International

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“…29 A flow diagram of all steps of the extraction is presented in Figure 2. Urine, serum, or bile (1 mL) was acidified by adding glacial acetic acid (20 μL) and extracted in acetonitrile (2 mL).…”

Section: Materials and Methodsmentioning

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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“…However, evidence for the formation of PCB sulfates in vivo was lacking until sulfate ester metabolites derived from PCB 3 were recently detected in serum and urine samples collected from male Sprague-Dawley rats exposed to PCB 3 by intraperitoneal injection or inhalation (Dhakal et al, 2013, Dhakal et al, 2012, Dhakal et al, 2014). Interestingly, PCB sulfates appeared to be major metabolites in these studies, far outweighing glucuronidation.…”

Section: Pcb Metabolism and Relevant Classes Of Pcb Metabolitesmentioning

confidence: 99%

Metabolism and metabolites of polychlorinated biphenyls

Grimm

Kania-Korwel

et al. 2015

Critical Reviews in Toxicology

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414

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The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity and thereby assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general and in humans in particular. The aim of this document is to provide an overview of PCB metabolism and to identify metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and sulfated metabolites, especially those that persist in human blood. Potential intracellular targets and health risks are also discussed.

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Sulfate Conjugates Are Urinary Markers of Inhalation Exposure to 4-Chlorobiphenyl (PCB3)

Cited by 31 publications

References 22 publications

Identification of a sulfate metabolite of PCB 11 in human serum

Identification of a sulfate metabolite of PCB 11 in human serum

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

Metabolism and metabolites of polychlorinated biphenyls

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