Disposition and metabolomic effects of 2,2′,5,5′-tetrachlorobiphenyl in female rats following intraperitoneal exposure

Bullert, Amanda; Li, Xueshu; Zhang, Chunyun; Lee, Kendra; Pulliam, Casey; Cagle, Brianna S.; Doorn, Jonathan A.; Klingelhutz, Aloysius J.; Robertson, Larry W.; Lehmler, Hans‐Joachim

doi:10.1016/j.etap.2023.104245

Cited by 3 publications

(9 citation statements)

References 110 publications

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“…These metabolites are metabolized to corresponding sulfates and methoxylated PCB metabolites by sulfotransferases (SULT) or COMT. Also, OH-PCB metabolites undergo chlorine displacement to form dechlorinated dihydroxylated PCB metabolites that undergo further biotransformation to sulfate conjugates and methoxylated PCBs, as reported. , This metabolism pathway is consistent with published in vitro and in vivo studies , and comparable to our previous work in rats intraperitoneally exposed to PCB52 . Importantly, the complex PCB52 metabolite profile observed in the lung is suggestive of the first-path metabolism of PCB52 in the lung.…”

Section: Resultssupporting

confidence: 90%

“…After intraperitoneal exposure to a synthetic PCB mixture, OH-PCBs were detected in the brains of dogs . Similarly, X1-OH-PCB52 and 4-OH-PCB52 were detected with a detection frequency of 20% in the rat brain 3 weeks after an intraperitoneal administration of a high PCB52 dose (100 mg/kg bw) . PCBs and OH-PCBs have also been detected in the brain of Macaca fuscata , with levels ranging from 6.7 to 31 pg/g, and in a small number of post-mortem human brain tissue samples .…”

Section: Resultsmentioning

confidence: 96%

“…Our results show that in both exposure groups X1-OH-PCB52 was detected in the adipose tissue of female but not male rats (Figure A; Table S7). After IP exposure to PCB52 in female rats, 4-OH-PCB52 was only detected in the adipose from one high-exposure animal . Furthermore, one study found traces of a meta-hydroxylated PCB metabolite in the adipose tissue in rats following subacute oral exposure to PCB95 .…”

Section: Resultsmentioning

confidence: 99%

“…Representative chromatograms and mass spectra showing the presence of one PCB sulfate, one OH-PCB sulfate, and one MeO-PCB sulfate in the lung are shown in Figure ; for chromatograms and mass spectra of other PCB52 metabolites in other compartments, see Figures S2–S8. It is noteworthy that the metabolite profiles detected in tissues and serum differ between IP administration vs inhalation of PCB52 . For example, 6 of 11 metabolites detected in the livers of rats exposed IP to PCB52 were not observed after inhalation exposure, whereas 2 of 7 metabolites were unique following PCB52 inhalation.…”

Section: Resultsmentioning

confidence: 99%

“…After IP exposure to PCB52 in female rats, 4-OH-PCB52 was only detected in the adipose from one high-exposure animal. 66 Furthermore, one study found traces of a meta-hydroxylated PCB metabolite in the adipose tissue in rats following subacute oral exposure to PCB95. 67 Other disposition studies detected OH-PCBs in the liver and serum but not the adipose tissue of mice exposed orally to repeated doses of PCB91 or PCB95, 48 , 68 , 69 likely because the analytical method used by this earlier study lacked sensitivity.…”

Section: Resultsmentioning

confidence: 99%

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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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