Clearance of polychlorinated biphenyl atropisomers is enantioselective in female C57Bl/6 mice.
Changes in the enantiomeric composition of polychlorinated biphenyls (PCBs) can not only be used to investigate environmental and biological transport processes, but also have human health implications because of enantiospecific adverse health effects. To further understand differences in the disposition of PCB atropisomers in vivo, the present study investigates the toxicokinetics of PCB atropisomers in female C57Bl/6 mice after oral administration of a mixture of several PCBs, including racemic PCBs 91, 95, 132, 136, 149, 174, and 176. On the Chirasil-Dex column, an enrichment of the second eluting atropisomers was generally observed, whereas only the first eluting atropisomers E1-PCB 95, (-)-PCB 132, and (-)-PCB 149 had half-lives that were distinctively longer compared to the second eluting atropisomers. The bioavailability normalized clearance of first eluting atropisomers in blood was faster compared to that of second eluting atropisomers. The opposite trend was observed for the accumulation factors in adipose tissue, which is consistent with the slower clearance of the first eluting atropisomer. The only exception was PCB 174, which showed no differences in the toxicokinetic parameters of both atropisomers. Together, the differences in the toxicokinetics of PCB atropisomers point toward enantioselective biotransformation processes as the origin of PCB's enantiomeric enrichment in mammals and, possibly, humans.
Kania-Korwel
Izabela
I
Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, Iowa 52242, USA.
El-Komy
Mohammed H M E
MH
Veng-Pedersen
Peter
P
Lehmler
Hans-Joachim
HJ
D000818:Animals; D001682:Biological Availability; D002849:Chromatography, Gas; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics* / Q000633:toxicity; D011786:Quality Control; D013237:Stereoisomerism
D011078:Polychlorinated Biphenyls
Environ Sci Technol. 2006 Jun 15;40(12):3696-703
16830529
J Chromatogr A. 2008 Oct 17;1207(1-2):146-54
18760792
Drug Metab Dispos. 1975 Sep-Oct;3(5):371-80
241618
Neurotoxicology. 1997;18(2):443-56
9291493
Biochem Pharmacol. 1983 Nov 1;32(21):3233-9
6416258
Biochem Pharmacol. 1989 Apr 15;38(8):1345-52
2495802
Chirality. 2007 Jan;19(1):56-66
17089340
Environ Res. 2003 Oct;93(2):167-76
12963401
Aquat Toxicol. 2006 Jun 15;78(2):176-85
16621064
Environ Sci Technol. 2006 Jun 15;40(12):3704-10
16830530
Drug Metab Dispos. 1982 Nov-Dec;10(6):657-61
6130918
Arch Environ Contam Toxicol. 1991 May;20(4):449-53
1906267
Environ Toxicol Chem. 2008 Feb;27(2):299-305
18348647
Chem Res Toxicol. 2009 Jan;22(1):201-7
18954145
Environ Sci Technol. 2002 Mar 15;36(6):1257-62
11944677
Environ Sci Technol. 2009 Jan 1;43(1):114-21
19209593
Toxicol Appl Pharmacol. 1997 Jun;144(2):340-7
9194418
Environ Res. 1992 Oct;59(1):202-16
1425510
J Clin Pharmacol. 1988 Jan;28(1):1-5
3280613
J Biol Chem. 1997 Jun 13;272(24):15145-53
9182535
Environ Res. 2005 Jul;98(3):284-302
15910784
Toxicol Appl Pharmacol. 1982 Sep 15;65(2):264-72
6817469
Toxicol Appl Pharmacol. 1982 Feb;62(2):294-306
6800066
Bull Environ Contam Toxicol. 1980 Aug;25(2):181-7
6775714
Toxicol Appl Pharmacol. 1983 Sep 15;70(2):262-72
6414105
Chemosphere. 2008 Jan;70(4):567-75
17727913
Arch Environ Contam Toxicol. 1977;5(3):257-78
405931
Chem Res Toxicol. 2008 Jun;21(6):1295-303
18494506
Toxicol Sci. 2005 Dec;88(2):400-11
16177234
Food Chem Toxicol. 2008 Feb;46(2):637-44
17950514
Toxicol Appl Pharmacol. 1980 May;53(3):377-88
6770494
Clin Pharmacol Ther. 1977 Nov;22(5 Pt 2):765-73
410580
Arch Environ Contam Toxicol. 2008 Oct;55(3):510-7
18437444
Environ Sci Technol. 2007 Apr 1;41(7):2153-8
17438756
Environ Sci Technol. 2010 Apr 15;44(8):2757-66
20384371
J Pharmacokinet Biopharm. 1977 Oct;5(5):513-31
925885
Chemosphere. 2006 Aug;64(8):1383-92
16442586
Environ Health Perspect. 1985 Sep;61:11-20
2998745