Journal article
Effect of pregnancy on the disposition of 2,2',3,5',6-pentachlorobiphenyl (PCB 95) atropisomers and their hydroxylated metabolites in female mice
Chemical research in toxicology, Vol.28(9), pp.1774-1783
09/21/2015
DOI: 10.1021/acs.chemrestox.5b00241
PMCID: PMC4579038
PMID: 26271003
Abstract
Chiral PCBs, such as PCB 95, are developmental neurotoxicants that undergo atropisomeric enrichment in nonpregnant adult mice. Because pregnancy is associated with changes in hepatic cytochrome P450 enzyme activity as well as lipid disposition and metabolism, this study investigates the effect of pregnancy on the maternal disposition of chiral PCBs. Female C57BL/6 mice (8 weeks old) were dosed daily beginning 2 weeks prior to conception and continuing throughout gestation and lactation (56 days total) with racemic PCB 95 (0, 0.1, 1.0, or 6.0 mg/kg body wt/day) in peanut butter. Levels and chiral signatures of PCB 95 and its hydroxylated metabolites (OH-PCBs) were determined in adipose, blood, brain, and liver. Tissue levels of PCB 95 increased 4- to 12-fold with increasing dose, with considerable enrichment of the second eluting atropisomer in all tissues (EF range 0.11 to 0.26). OH-PCBs displayed atropisomeric enrichment in blood and liver but were not detected in adipose and brain. Levels of PCB 95 and its metabolites were 2- to 11-fold lower in pregnant dams relative to those previously reported in nonpregnant age-matched female mice; however, PCB 95 and OH-PCB profiles and chiral signatures were similar between both studies. In contrast, human brain samples contained racemic PCB 95 residues (EF = 0.50). These results demonstrate that changes in cytochrome P450 enzyme activity and lipid disposition during pregnancy reduce the PCB body burden in dams but do not affect metabolite profiles or chiral signatures. The differences in chiral signatures between mice and humans suggest species-specific differences in atropisomeric disposition, the toxicological significance of which remains to be determined.
Details
- Title: Subtitle
- Effect of pregnancy on the disposition of 2,2',3,5',6-pentachlorobiphenyl (PCB 95) atropisomers and their hydroxylated metabolites in female mice
- Creators
- Izabela Kania-Korwel - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52242-5000, United StatesChristopher D Barnhart - Department of Molecular Biosciences, School of Veterinary Medicine, University of California , Davis, California 95616, United StatesPamela J Lein - Department of Molecular Biosciences, School of Veterinary Medicine, University of California , Davis, California 95616, United StatesHans-Joachim Lehmler - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52242-5000, United States
- Resource Type
- Journal article
- Publication Details
- Chemical research in toxicology, Vol.28(9), pp.1774-1783
- DOI
- 10.1021/acs.chemrestox.5b00241
- PMID
- 26271003
- PMCID
- PMC4579038
- NLM abbreviation
- Chem Res Toxicol
- ISSN
- 0893-228X
- eISSN
- 1520-5010
- Publisher
- United States
- Grant note
- P30 ES005605 / NIEHS NIH HHS R56 ES014901 / NIEHS NIH HHS R01 ES017425 / NIEHS NIH HHS P42 ES013661 / NIEHS NIH HHS P42 ES004699 / NIEHS NIH HHS ES04699 / NIEHS NIH HHS ES013661 / NIEHS NIH HHS ES017425 / NIEHS NIH HHS T32 ES007059 / NIEHS NIH HHS ES007059 / NIEHS NIH HHS ES014901 / NIEHS NIH HHS ES05605 / NIEHS NIH HHS R01 ES014901 / NIEHS NIH HHS
- Language
- English
- Date published
- 09/21/2015
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
- Record Identifier
- 9984000930302771
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