Toxicokinetic mixture interactions between chlorinated aromatic hydrocarbons in the liver of the C57BL/6J mouse: 2. Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs).
Six groups of C57BL/6J mice received single oral doses of 1.5-10.6 nmol/kg 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PnCDD), 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (HxCDD) or 2,3,4,7,8-pentachlorodibenzofuran (PnCDF) as single compounds or in combination with 300 mumol/kg 2,2',4,4',5,5'-hexachlorobiphenyl (HxCB). Two other groups of mice received a mixture of the first three compounds, either with or without HxCB. The hepatic deposition and elimination of the compounds and their CYP1a dependent 7-ethoxyresorufin-O-deethylation (EROD) activity were studied until day 175. Interactive effects on the hepatic deposition of PnCDD were observed in most of the mixed dose groups. For HxCDD and PnCDF interactive effects were either very small or absent. No interactive effects were observed on hepatic elimination rates of PnCDD, HxCDD or PnCDF. No evidence was found for the influence of HxCB cotreatment on the hepatic concentration-response curves of the three compounds or their mixture. Based on the results from the present study it is concluded that PCDDs, PCDFs and PCBs may influence each other's, toxicokinetics when administered in mixtures.
De Jongh
J
J
Research Institute of Toxicology, University of Utrecht, The Netherlands.
Nieboer
R
R
Schröders
I
I
Seinen
W
W
Van den Berg
M
M
D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004347:Drug Interactions; D006843:Hydrocarbons, Chlorinated / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010088:Oxidoreductases / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D011108:Polymers / Q000493:pharmacokinetics / Q000633:toxicity*
D001572:Benzofurans; D006843:Hydrocarbons, Chlorinated; D000072317:Polychlorinated Dibenzodioxins; D011108:Polymers; C016068:polychlorodibenzofuran; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1