Disposition of PCB 11 in Mice Following Acute Oral Exposure

Zhang, Chun Yun; Klocke, Carolyn; Lein, Pamela J.; Lehmler, Hans‐Joachim

doi:10.1021/acs.chemrestox.1c00067

Cited by 9 publications

(5 citation statements)

References 6 publications

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“…A subset of brain tissue samples N = 18) was selected for Nt-LCMS screening for OH-PCB using a modified protocol based on earlier studies. 58 − 60 Briefly, human brain tissues (∼0.5 g) were homogenized in glass tubes with 2 mL of Milli-Q water using a TissueRuptor (Qiagen). The homogenates were spiked with 4′-chloro-3′-fluoro-4-hydroxy-biphenyl and the corresponding PCB sulfate (100 ng of each) in acetonitrile.…”

Section: Methodsmentioning

confidence: 99%

Assessment of Polychlorinated Biphenyls and Their Hydroxylated Metabolites in Postmortem Human Brain Samples: Age and Brain Region Differences

Hefti

Marek

et al. 2022

Environ. Sci. Technol.

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Exposure to polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) has been implicated in neurodevelopmental disorders. However, the distribution of PCBs and OH-PCBs in the human brain has not been characterized. This study investigated the age-, sex-, and brain region-specific distribution of all 209 PCBs using gaschromatography–tandem mass spectrometry (GC–MS/MS) in neonatal ( N = 7) and adult ( N = 7) postmortem brain samples. OH-PCB analyses were performed by GC–MS/MS (as methylated derivatives) and, in a subset of samples, by nontarget liquid chromatography high-resolution mass spectrometry (Nt-LCMS). Fourteen higher chlorinated PCB congeners were observed with a detection frequency >50%. Six lower chlorinated PCBs were detected with a detection frequency >10%. Higher chlorinated PCBs were observed with higher levels in samples from adult versus younger donors. PCB congener profiles from adult donors showed more similarities across brain regions and donors than younger donors. We also assess the potential neurotoxicity of the PCB residues in the human brain with neurotoxic equivalency (NEQ) approaches. The median ΣNEQs, calculated for the PCB homologues, were 40-fold higher in older versus younger donors. Importantly, lower chlorinated PCBs made considerable contributions to the neurotoxic potential of PCB residues in some donors. OH-PCBs were identified for the first time in a small number of human brain samples by GC–MS/MS and Nt-LCMS analyses, and all contained four or fewer chlorine.

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Section: Methodsmentioning

confidence: 99%

Assessment of Polychlorinated Biphenyls and Their Hydroxylated Metabolites in Postmortem Human Brain Samples: Age and Brain Region Differences

Hefti

Marek

et al. 2022

Environ. Sci. Technol.

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“…One PCB sulfate was found in the liver (DF 8%) and serum (DF > 58%). Similarly, PCB sulfates have been detected in the liver and serum of rodents following acute inhalation exposure to PCB3 , or oral exposure to PCB11, as well as in the serum of human populations. , …”

Section: Resultsmentioning

confidence: 98%

“…These metabolites can also have detrimental effects on the brain . Therefore, we employed a published LC-HRMS technique ,, to comprehensively examine the PCB52 metabolites in selected tissues following acute PCB52 inhalation. The objective was to elucidate the metabolic pathway of PCB52 in rats after the inhalation of PCB52.…”

Section: Resultsmentioning

confidence: 99%

“…Hydroxylated PCB sulfates have been detected in rat urine following inhalation of PCB3 83 and in the liver and serum of mice orally exposed to PCB11. 73 These metabolites can be formed by the sulfation of PCB catechol metabolites, 83 which are formed in a two-step oxidation process by rat cytochrome P450 enzymes. 86 , 87 Alternatively, PCB sulfates can be oxidized to OH-PCB sulfates, as shown after intravenous injection of a PCB11 sulfate in rats.…”

Section: Resultsmentioning

confidence: 99%

“…83 One PCB sulfate was found in the liver (DF 8%) and serum (DF > 58%). Similarly, PCB sulfates have been detected in the liver and serum of rodents following acute inhalation exposure to PCB3 28,84 or oral exposure to PCB11, 74 as well as in the serum of human populations. 85,86 The LC-HRMS analysis also identified sulfated, methoxylated, or dihydroxylated PCB52 metabolites in the liver and serum (Figure S9; Table 1).…”

Section: Environmental Science and Technologymentioning

confidence: 97%

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Distribution of 2,2′,5,5′-Tetrachlorobiphenyl (PCB52) Metabolites in Adolescent Rats after Acute Nose-Only Inhalation Exposure

Bullert,

Li,

Gautam

et al. 2024

Environ. Sci. Technol.

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Inhalation of PCB-contaminated air is increasingly recognized as a route for PCB exposure. Because limited information about the disposition of PCBs following inhalation exposure is available, this study investigated the disposition of 2,2′,5,5′-tetrachlorobiphenyl (PCB52) and its metabolites in rats following acute, nose-only inhalation of PCB52. Male and female Sprague–Dawley rats (50–58 days of age, 210 ± 27 g; n = 6) were exposed for 4 h by inhalation to approximately 14 or 23 μg/kg body weight of PCB52 using a nose-only exposure system. Sham animals (n = 6) were exposed to filtered lab air. Based on gas chromatography-tandem mass spectrometry (GC-MS/MS), PCB52 was present in adipose, brain, intestinal content, lung, liver, and serum. 2,2′,5,5′-Tetrachlorobiphenyl-4-ol (4-OH-PCB52) and one unknown monohydroxylated metabolite were detected in these compartments except for the brain. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis identified several metabolites, including sulfated, methoxylated, and dechlorinated PCB52 metabolites. These metabolites were primarily found in the liver (7 metabolites), lung (9 metabolites), and serum (9 metabolites) due to the short exposure time. These results demonstrate for the first time that complex mixtures of sulfated, methoxylated, and dechlorinated PCB52 metabolites are formed in adolescent rats following PCB52 inhalation, laying the groundwork for future animal studies of the adverse effects of inhaled PCB52.

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A review of PCB-11 and other unintentionally produced PCB congeners in outdoor air

Mastin

Harner

Schuster

et al. 2022

Atmospheric Pollution Research

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Disposition of PCB 11 in Mice Following Acute Oral Exposure

Cited by 9 publications

References 6 publications

Assessment of Polychlorinated Biphenyls and Their Hydroxylated Metabolites in Postmortem Human Brain Samples: Age and Brain Region Differences

Assessment of Polychlorinated Biphenyls and Their Hydroxylated Metabolites in Postmortem Human Brain Samples: Age and Brain Region Differences

Distribution of 2,2′,5,5′-Tetrachlorobiphenyl (PCB52) Metabolites in Adolescent Rats after Acute Nose-Only Inhalation Exposure

A review of PCB-11 and other unintentionally produced PCB congeners in outdoor air

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