Uptake, Elimination and Metabolism of Brominated Dibenzofurans in Mice
Polybrominated dibenzofurans (PBDFs) are major brominated dioxins in the environment, but information on their bioaccumulation potential and toxicokinetics is limited. This study conducted oral exposure experiments with C57BL/6J mice to investigate the uptake ratios, distribution in the liver, plasm...
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2024-09-01
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| author | Nguyen Minh Tue Eiki Kimura Fumihiko Maekawa Akitoshi Goto Naoto Uramaru Tatsuya Kunisue Go Suzuki |
| author_facet | Nguyen Minh Tue Eiki Kimura Fumihiko Maekawa Akitoshi Goto Naoto Uramaru Tatsuya Kunisue Go Suzuki |
| author_sort | Nguyen Minh Tue |
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| description | Polybrominated dibenzofurans (PBDFs) are major brominated dioxins in the environment, but information on their bioaccumulation potential and toxicokinetics is limited. This study conducted oral exposure experiments with C57BL/6J mice to investigate the uptake ratios, distribution in the liver, plasma and brain, metabolism, and elimination kinetics of four bromine/chlorine-substituted dibenzofurans (TrBDF: 2,3,8-tribromo, TeBDF: 2,3,7,8-tetrabromo, PeBDF: 1,2,3,7,8-pentabromo, TrBCDF: 2,3,7-tribromo-8-chloro) in comparison with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The hepatic uptake ratios of 2,3,7,8-substituted dibenzofurans were lower than that of TCDD (up to 84% of the administered doses) and decreased with the number of Br substitutions (42%, 33%, and 29% for TrBCDF, TeBDF, and PeBDF, respectively). The brain uptake ratios of these dibenzofurans were less than 0.05%, and the plasma-to-brain transfer ratio also decreased with the Br number. All 2,3,7,8-substituted compounds were eliminated from the liver following first-order kinetics, with half-times in the order of TrBCDF (5.6 days) < TeBDF (8.8 days) ≈ TCDD (8.7 days) < PeBDF (13 days). The non-2,3,7,8-substituted TrBDF was poorly retained in the liver (<0.01% of the dose at 1 day) and rapidly eliminated following two-phase kinetics. All dibenzofurans were metabolised into monohydroxylated products in the liver, but the contribution of this metabolic pathway to hepatic elimination was only significant for TrBDF. As the toxic effects of dioxin-like compounds are influenced by their biological persistence, the slow elimination of TrBCDF, TeBDF, and PeBDF observed in this study suggests that exposure risk of brominated dibenzofurans may be underestimated using the toxic equivalency factors of the less persistent chlorinated analogues. |
| format | Article |
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| spelling | doaj-art-9c464b9b84bc42eb9a4de15e1865d6b22025-08-20T01:55:53ZengMDPI AGToxics2305-63042024-09-0112965610.3390/toxics12090656Uptake, Elimination and Metabolism of Brominated Dibenzofurans in MiceNguyen Minh Tue0Eiki Kimura1Fumihiko Maekawa2Akitoshi Goto3Naoto Uramaru4Tatsuya Kunisue5Go Suzuki6Center for Marine Environmental Studies (CMES), Ehime University, 2-5 Bunkyo-cho, Matsuyama 790-8577, JapanHealth and Environmental Risk Division, National Institute for Environmental Studies (NIES), 16-2 Onogawa, Tsukuba 305-8506, JapanHealth and Environmental Risk Division, National Institute for Environmental Studies (NIES), 16-2 Onogawa, Tsukuba 305-8506, JapanCenter for Marine Environmental Studies (CMES), Ehime University, 2-5 Bunkyo-cho, Matsuyama 790-8577, JapanDivision of Pharmaceutical Health Biosciences, Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kitaadachi, Saitama 362-0806, JapanCenter for Marine Environmental Studies (CMES), Ehime University, 2-5 Bunkyo-cho, Matsuyama 790-8577, JapanMaterial Cycles Division, NIES, 16-2 Onogawa, Tsukuba 305-8506, JapanPolybrominated dibenzofurans (PBDFs) are major brominated dioxins in the environment, but information on their bioaccumulation potential and toxicokinetics is limited. This study conducted oral exposure experiments with C57BL/6J mice to investigate the uptake ratios, distribution in the liver, plasma and brain, metabolism, and elimination kinetics of four bromine/chlorine-substituted dibenzofurans (TrBDF: 2,3,8-tribromo, TeBDF: 2,3,7,8-tetrabromo, PeBDF: 1,2,3,7,8-pentabromo, TrBCDF: 2,3,7-tribromo-8-chloro) in comparison with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The hepatic uptake ratios of 2,3,7,8-substituted dibenzofurans were lower than that of TCDD (up to 84% of the administered doses) and decreased with the number of Br substitutions (42%, 33%, and 29% for TrBCDF, TeBDF, and PeBDF, respectively). The brain uptake ratios of these dibenzofurans were less than 0.05%, and the plasma-to-brain transfer ratio also decreased with the Br number. All 2,3,7,8-substituted compounds were eliminated from the liver following first-order kinetics, with half-times in the order of TrBCDF (5.6 days) < TeBDF (8.8 days) ≈ TCDD (8.7 days) < PeBDF (13 days). The non-2,3,7,8-substituted TrBDF was poorly retained in the liver (<0.01% of the dose at 1 day) and rapidly eliminated following two-phase kinetics. All dibenzofurans were metabolised into monohydroxylated products in the liver, but the contribution of this metabolic pathway to hepatic elimination was only significant for TrBDF. As the toxic effects of dioxin-like compounds are influenced by their biological persistence, the slow elimination of TrBCDF, TeBDF, and PeBDF observed in this study suggests that exposure risk of brominated dibenzofurans may be underestimated using the toxic equivalency factors of the less persistent chlorinated analogues.https://www.mdpi.com/2305-6304/12/9/656brominated dioxinsmetabolitesmousetissue distributiontoxicokinetics |
| spellingShingle | Nguyen Minh Tue Eiki Kimura Fumihiko Maekawa Akitoshi Goto Naoto Uramaru Tatsuya Kunisue Go Suzuki Uptake, Elimination and Metabolism of Brominated Dibenzofurans in Mice Toxics brominated dioxins metabolites mouse tissue distribution toxicokinetics |
| title | Uptake, Elimination and Metabolism of Brominated Dibenzofurans in Mice |
| title_full | Uptake, Elimination and Metabolism of Brominated Dibenzofurans in Mice |
| title_fullStr | Uptake, Elimination and Metabolism of Brominated Dibenzofurans in Mice |
| title_full_unstemmed | Uptake, Elimination and Metabolism of Brominated Dibenzofurans in Mice |
| title_short | Uptake, Elimination and Metabolism of Brominated Dibenzofurans in Mice |
| title_sort | uptake elimination and metabolism of brominated dibenzofurans in mice |
| topic | brominated dioxins metabolites mouse tissue distribution toxicokinetics |
| url | https://www.mdpi.com/2305-6304/12/9/656 |
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