Congener-specific toxicokinetics of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in black-eared kites (Milvus migrans): cytochrome P4501A-dependent hepatic sequestration.
Concentrations of dioxins and related compounds (DRCs), such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs), were determined in black-eared kites (BEKs; Milvus migrans) collected from the Kanto district in Japan. Total 2,3,7,8-tetra-CDD toxic equivalents (TEQs) were in the range of 99 to 3,800 pg/g lipid weight in the liver and 42 to 760 pg/g lipid weight in the pectoral muscle. Three congeners, including PCB 126, 2,3,4,7,8-penta-CDF, and 1,2,3,7,8-penta-CDD, made a greater contribution to total TEQs in both tissues. Levels of ethoxyresorufin-O-deethylase activity and a cross-reactive protein with anti-rat cytochrome P4501A (CYP1A) polyclonal antibodies showed no significant correlation with hepatic TEQs. This may be attributed to low sensitivity and insufficient TEQ levels to cause CYP1A induction, high metabolic potential of a series of congeners, and influence of CYP1A inducers other than DRCs. Most of the PCDD/ Fs and non-ortho Co-PCBs exhibited a total TEQ- and CYP1A-dependent increase in the liver to muscle concentration ratios, implying their concentration-dependent hepatic sequestration in which CYP1A was involved. Comparison of the toxicokinetics in avian species revealed that BEKs possibly have higher potentials than common cormorants for metabolizing and sequestering certain congeners in the liver in terms of hepatic concentration profiles and liver:muscle concentration ratios, respectively. These results clearly indicate that the toxicokinetics of DRCs is congener-, tissue-, and species-specific as well as concentration-dependent. Therefore, CYP1A expression is one of the critical factors that determine the toxicokinetics in wild avian species.
Kubota
Akira
A
Center for Marine Environmental Studies, Ehime University, 2-5 Bunkyo-cho, Matsuyama 790-8577, Japan.
Iwata
Hisato
H
Tanabe
Shinsuke
S
Yoneda
Kumiko
K
Tobata
Sachiko
S
D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072338:Dibenzofurans, Polychlorinated; D046093:Falconiformes / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000201:enzymology; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls