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Pharmacology & ToxicologybioRxiv

Disposition and Metabolomic Effects of 2,2',5,5'-Tetrachlorobiphenyl in Female Rats Following Intraperitoneal Exposure

A. Bullert, X. Li, C. Zhang, K. Lee, C. F. Pulliam, B. S. Cagle, J. A. Doorn, A. J. Klingelhutz, L. W. Robertson, H.-J. Lehmler

Abstract

The disposition and toxicity of lower chlorinated PCBs (LC-PCBs) with less than five chlorine substituents have received little attention. This study characterizes the distribution and metabolomic effects of PCB 52, an LC-PCB found in indoor and outdoor air, three weeks after intraperitoneal exposure of female Sprague Dawley rats to 0, 1, 10, or 100 mg/kg BW. PCB 52 exposure did not affect overall body weight. Gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis identified PCB 52 in all tissues investigated. Hydroxylated, sulfated, and methylated PCB metabolites, identified using GC-MS/MS and nontarget liquid chromatography-high resolution mass spectrometry (Nt-LCMS), were primarily found in the serum and liver of rats exposed to 100 mg/kg BW. Metabolomic analysis revealed minor effects on L-cysteine, glycine, cytosine, sphingosine, thymine, linoleic acid, orotic acid, L-histidine, and erythrose serum levels. Thus, the metabolism of PCB 52 and its effects on the metabolome must be considered in toxicity studies. HighlightsO_LIPCB 52 was present in adipose, brain, liver, and serum 3 weeks after PCB exposure C_LIO_LILiver and serum contained hydroxylated, sulfated, and methylated PCB 52 metabolites C_LIO_LIMetabolomics analysis revealed minor changes in endogenous serum metabolites C_LIO_LILevels of dopamine and its metabolites in the brain were not affected by PCB 52 C_LI

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02 /Specification & Classification

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