| Autor: |
Dunnick JK; Toxicology Branch, National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, NC, 27709-2233, USA. dunnickj@niehs.nih.gov., Shockley KR; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA., Pandiri AR; Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA., Kissling GE; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA., Gerrish KE; Molecular Genomics Core, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA., Ton TV; Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA., Wilson RE; Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA., Brar SS; Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA., Brix AE; EPL, Inc., Research Triangle Park, NC, 27709, USA., Waidyanatha S; Toxicology Operations Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA., Mutlu E; Toxicology Operations Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA., Morgan DL; Toxicology Branch, National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, NC, 27709-2233, USA. |
| Abstrakt: |
Pentabromodiphenyl ethers (PBDE) are found in human tissue, in household dust, and in the environment, and a particular concern is the potential for the induction of cancer pathways from these fat-soluble persistent organic pollutants. Only one PBDE cancer study has been conducted and that was for a PBDE mixture (DE-71). Because it is not feasible to test all PBDE congeners in the environment for cancer potential, it is important to develop a set of biological endpoints that can be used in short-term toxicity studies to predict disease outcome after long-term exposures. In this study, PBDE-47 was selected as the test PBDE congener to evaluate and compare toxicity to that of the carcinogenic PBDE mixture. The toxicities of PBDE-47 and the PBDE mixture were evaluated at PND 22 in Wistar Han rat (Crl: WI (Han)) pups after in utero/postnatal exposure (0, 0.1, 15, or 50 mg/kg; dams, GD6-21; pups, PND 12-PND 21; oral gavage daily dosing). By PND 22, PBDE-47 caused centrilobular hypertrophy and fatty change in liver, and reduced serum thyroxin (T 4 ) levels; similar effects were also observed after PBDE mixture exposure. Transcriptomic changes in the liver included induction of cytochrome p450 transcripts and up-regulation of Nrf2 antioxidant pathway transcripts and ABC membrane transport transcripts. Decreases in other transport transcripts (ABCG5 & 8) provided a plausible mechanism for lipid accumulation, characterized by a treatment-related liver fatty change after PBDE-47 and PBDE mixture exposure. The benchmark dose calculation based on liver transcriptomic data was generally lower for PBDE-47 than for the PBDE mixture. The up-regulation of the Nrf2 antioxidant pathway and changes in metabolic transcripts after PBDE-47 and PBDE mixture exposure suggest that PBDE-47, like the PBDE mixture (NTP 2016, TR 589), could be a liver toxin/carcinogen after long-term exposure. |
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