Disposition and Toxicity of 2,2’,5,5’-Tetrachlorobiphenyl in Female Rats Following Intraperitoneal Exposure
biorxiv(2023)
摘要
The disposition and toxicity of lower chlorinated PCBs (LC-PCBs) with less than five chlorine substituents have received little attention to date. This study characterizes the distribution 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 PCB 52/kg BW. PCB 52 exposure did not affect body or organ weights. PCB 52, measured using gas chromatography-tandem mass spectrometry (GC-MS/MS), was detected in all tissue. Hydroxylated, sulfated, and methylated PCB metabolites, identified using GC-MS/MS and nontarget liquid chromatography-high resolution mass spectrometry, 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. Based on these results, PCB 52 toxicity studies need to account for its complex metabolism in vivo .
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Highlights
### Competing Interest Statement
The authors have declared no competing interest.
* IP
: intraperitoneal
PCB
: polychlorinated biphenyl
BW
: body weight
Nt-LCMS
: Nontarget; liquid chromatography-high resolution mass spectrometric
GC-MS/MS
: Gas chromatograph mass spectrometric
UPLC-QTof-MS
: Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometric
QC
: quality control
PCA
: principle component analysis
ANOVA
: analysis of variance
DA
: dopamine
DOPAC
: 3,4-Dihydroxyphenylacetic acid
DOPAL
: 3,4-dihydroxyphenylacetaldehyde
PLS-DA
: partial least squares-discriminant analysis (PLS-DA)
VIP
: variable importance in projection
CYP
: cytochrome P450 enzyme
SD
: Sprague-Dawley
MOC
: methyoxyamine hydrochloride
TMS
: N,O-Bis(trimethylsilyl)trifluoroacetamide
SPE
: solid phase extraction
SULT
: sulfotransferase
COMT
: catechol-O-methyltransferase
ND
: non-detect
[1]: pending:yes
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