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

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

“…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.…”

“…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 .…”

“…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 .…”

“…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.…”

“…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.…”