title: Chiral polychlorinated biphenyls: absorption, metabolism and excretion--a review.
abstract: Seventy eight out of the 209 possible polychlorinated biphenyl (PCB) congeners are chiral, 19 of which exist under ambient conditions as stable rotational isomers that are non-superimposable mirror images of each other. These congeners (C-PCBs) represent up to 6 % by weight of technical PCB mixtures and undergo considerable atropisomeric enrichment in wildlife, laboratory animals, and humans. The objective of this review is to summarize our current knowledge of the processes involved in the absorption, metabolism, and excretion of C-PCBs and their metabolites in laboratory animals and humans. C-PCBs are absorbed and excreted by passive diffusion, a process that, like other physicochemical processes, is inherently not atropselective. In mammals, metabolism by cytochrome P450 (P450) enzymes represents a major route of elimination for many C-PCBs. In vitro studies demonstrate that C-PCBs with a 2,3,6-trichlorosubstitution pattern in one phenyl ring are readily oxidized to hydroxylated PCB metabolites (HO-PCBs) by P450 enzymes, such as rat CYP2B1, human CYP2B6, and dog CYP2B11. The oxidation of C-PCBs is atropselective, thus resulting in a species- and congener-dependent atropisomeric enrichment of C-PCBs and their metabolites. This atropisomeric enrichment of C-PCBs and their metabolites likely plays a poorly understood role in the atropselective toxicity of C-PCBs and, therefore, warrants further investigation.
authors: Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA.
authors: Izabela
authors: I
authors: Kania-Korwel
authors: Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, UI Research Park, Iowa City, IA, 52242, USA. hans-joachim-lehmler@uiowa.edu.
authors: Hans-Joachim
authors: HJ
authors: Lehmler
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004785:Environmental Pollutants / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D011078:Polychlorinated Biphenyls / Q000737:chemistry* / Q000493:pharmacokinetics*; D013237:Stereoisomerism
chemical_list: D004785:Environmental Pollutants; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls
keywords: Biotransformation; Chirality; Cytochrome P450 enzyme; Enantioselective; Oxidation
references: Toxicol Appl Pharmacol. 1983 Sep 15;70(2):262-72
references: 6414105
references: Arch Environ Contam Toxicol. 2003 Jan;44(1):97-106
references: 12434224
references: Toxicol Appl Pharmacol. 2003 Mar 15;187(3):168-77
references: 12662900
references: Environ Int. 2014 Feb;63:92-100
references: 24275706
references: Rocz Panstw Zakl Hig. 2004;55(4):313-24
references: 19097581
references: Environ Pollut. 2003;126(2):169-78
references: 12927488
references: Environ Sci Technol. 2012 Sep 4;46(17):9653-62
references: 22846166
references: Biochem Pharmacol. 1989 Apr 15;38(8):1345-52
references: 2495802
references: Environ Sci Technol. 2006 Dec 15;40(24):7649-55
references: 17256508
references: Environ Sci Technol. 2014 Feb 18;48(4):2436-44
references: 24467194
references: Bull Environ Contam Toxicol. 1979 Jan;21(1-2):273-8
references: 109143
references: J Chromatogr A. 2008 Oct 17;1207(1-2):146-54
references: 18760792
references: Chem Res Toxicol. 2006 Jan;19(1):92-101
references: 16411661
references: Toxicol Sci. 2005 Dec;88(2):400-11
references: 16177234
references: Chem Res Toxicol. 1999 Aug;12(8):690-9
references: 10458702
references: J Intern Med. 2014 Sep;276(3):248-59
references: 24428778
references: Environ Health Perspect. 2004 Mar;112(3):291-4
references: 14998742
references: Environ Sci Technol. 2010 Apr 15;44(8):2822-7
references: 19957996
references: Proc Soc Exp Biol Med. 1985 May;179(1):116-22
references: 3921971
references: J Biol Chem. 1983 Jul 10;258(13):8304-11
references: 6408087
references: Chem Res Toxicol. 2009 Jan;22(1):201-7
references: 18954145
references: Chirality. 2005 May 15;17(5):266-80
references: 15844204
references: Environ Health Perspect. 2003 Mar;111(3):357-576
references: 12611666
references: Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9725-30
references: 19497881
references: Am Ind Hyg Assoc J. 1987 Mar;48(3):257-64
references: 3107363
references: Environ Health Perspect. 2001 Jul;109(7):731-7
references: 11485873
references: Biochem Pharmacol. 1991 Mar 15-Apr 1;41(6-7):915-22
references: 1901208
references: Environ Int. 2012 Jul;42:138-43
references: 21764134
references: Biochem Biophys Res Commun. 1979 Nov 28;91(2):475-83
references: 42397
references: Chem Res Toxicol. 2011 Dec 19;24(12):2249-57
references: 22026639
references: Environ Sci Technol. 2009 Jan 1;43(1):114-21
references: 19209593
references: J Neurol Sci. 2011 Sep 15;308(1-2):9-15
references: 21679971
references: Environ Sci Technol. 2006 Jun 15;40(12):3704-10
references: 16830530
references: Annu Rev Pharmacol Toxicol. 2003;43:149-73
references: 12171978
references: Environ Sci Technol. 2011 Nov 15;45(22):9590-6
references: 21966948
references: Drug Metab Dispos. 1978 Sep-Oct;6(5):584-90
references: 30609
references: Environ Int. 2010 Aug;36(6):506-13
references: 20452025
references: Arch Environ Contam Toxicol. 2008 Oct;55(3):510-7
references: 18437444
references: Environ Res. 2003 Oct;93(2):167-76
references: 12963401
references: Chemosphere. 1995 Jun;30(11):2079-85
references: 7620847
references: Environ Sci Technol. 2012 Oct 16;46(20):11393-401
references: 22974126
references: Rev Environ Health. 2006 Jan-Mar;21(1):1-23
references: 16700427
references: Br J Ind Med. 1981 Feb;38(1):55-60
references: 6451237
references: Environ Sci Technol. 2007 Apr 1;41(7):2153-8
references: 17438756
references: Toxicol Appl Pharmacol. 1980 May;53(3):389-98
references: 6770495
references: Xenobiotica. 2013 Nov;43(11):933-47
references: 23581876
references: Environ Health Perspect. 2010 Jun;118(6):796-802
references: 20146964
references: J Chromatogr A. 2001 Jan 12;906(1-2):275-99
references: 11215892
references: Environ Sci Technol. 2011 Oct 1;45(19):8298-305
references: 21863805
references: Xenobiotica. 2005 Apr;35(4):319-30
references: 16019954
references: Environ Sci Technol. 2013;47(21):12184-92
references: 24060104
references: Environ Int. 2014 May;66:38-43
references: 24518434
references: Environ Sci Technol. 2010 Apr 15;44(8):2757-66
references: 20384371
references: Chemosphere. 2008 Jan;70(4):567-75
references: 17727913
references: Regul Toxicol Pharmacol. 2002 Jun;35(3):289-95
references: 12202044
references: Chemosphere. 2006 May;63(8):1368-76
references: 16289232
references: Crit Rev Toxicol. 2006 Mar;36(3):253-89
references: 16686424
references: Chem Res Toxicol. 2013 Nov 18;26(11):1642-51
references: 24107130
references: Biochem Pharmacol. 1983 Nov 1;32(21):3233-9
references: 6416258
references: Pharmacogenomics. 2007 Jul;8(7):743-59
references: 17638512
references: Biochem Pharmacol. 1986 Jan 15;35(2):297-306
references: 3080006
references: Science. 1974 Aug 16;185(4151):573-82
references: 4841570
references: Environ Sci Technol. 2002 Jul 1;36(13):2833-8
references: 12144255
references: Neurotoxicology. 1998 Aug-Oct;19(4-5):517-25
references: 9745906
references: Crit Rev Toxicol. 1996 Nov;26(6):709-37
references: 8958469
references: Environ Sci Technol. 2010 Sep 1;44(17):6893-900
references: 20698547
references: Drug Metab Dispos. 2005 Mar;33(3):373-80
references: 15608140
references: Chemosphere. 1995 Jan;30(2):293-306
references: 7874475
references: J Phys Chem A. 2012 Sep 20;116(37):9340-6
references: 22917060
references: Chem Res Toxicol. 2008 Jun;21(6):1295-303
references: 18494506
references: Science. 1982 Aug 13;217(4560):645-7
references: 6806905
references: Chem Cent J. 2013 Dec 22;7(1):183
references: 24360245
references: J Chromatogr A. 2013 Feb 22;1278:133-44
references: 23347976
references: Toxicol Appl Pharmacol. 1982 Feb;62(2):317-24
references: 6800067
references: Chemosphere. 2005 Aug;60(6):731-9
references: 15964056
references: Environ Toxicol Chem. 2004 Oct;23(10):2324-36
references: 15511095
references: Front Neuroendocrinol. 2010 Oct;31(4):479-96
references: 20609372
references: Toxicology. 2012 Mar 11;293(1-3):115-22
references: 22281205
references: Chirality. 2007 Jan;19(1):56-66
references: 17089340
references: Atmos Environ (1994). 2010 Apr;44(12):1550-1557
references: 21918637
references: Toxicol Sci. 2013 Dec;136(2):500-13
references: 24014653
references: Environ Health Perspect. 1998 Oct;106(10):633-41
references: 9755138
references: Chemosphere. 2007 Apr;67(9):S22-7
references: 17215020
references: Environ Toxicol Pharmacol. 2008 Mar;25(2):179-82
references: 21783856
references: Environ Sci Pollut Res Int. 2014 Jan;21(2):998-1009
references: 23852585
references: Toxicol Sci. 2011 Dec;124(2):261-77
references: 21920951
references: Food Chem Toxicol. 2008 Feb;46(2):637-44
references: 17950514
references: Chem Biol Interact. 1982 Jun;40(2):233-45
references: 6805966
references: Environ Sci Technol. 2010 Apr 15;44(8):2828-35
references: 20384376
references: J Lipid Res. 1996 May;37(5):950-61
references: 8725148
references: Science. 1967 Sep 29;157(3796):1524-30
references: 6038165
references: Chem Res Toxicol. 2004 Dec;17(12):1684-91
references: 15606145
references: Environ Sci Technol. 2004 Mar 15;38(6):1662-6
references: 15074672
references: Xenobiotica. 2005 Jan;35(1):85-96
references: 15788370
references: Pharmacol Ther. 2010 Feb;125(2):260-85
references: 19931307
references: Toxicol Sci. 2014 Apr;138(2):379-92
references: 24385416
references: Sci Total Environ. 2013 Aug 1;458-460:27-35
references: 23639909
references: Environ Int. 2010 Nov;36(8):884-92
references: 19923000
references: Curr Opin Pediatr. 2008 Apr;20(2):198-204
references: 18332718
references: Environ Sci Technol. 2003 Mar 15;37(6):1100-7
references: 12680661
references: Toxicol Lett. 2005 Apr 28;156(3):391-400
references: 15763638
references: Br J Ind Med. 1981 Feb;38(1):49-54
references: 6781529
references: Chem Res Toxicol. 1996 Apr-May;9(3):623-9
references: 8728508
references: Toxicol Appl Pharmacol. 2006 Oct 1;216(1):157-67
references: 16784763
references: Toxicol Appl Pharmacol. 1980 May;53(3):377-88
references: 6770494
references: Fukuoka Igaku Zasshi. 2013 Apr;104(4):161-9
references: 23858795