1. Evaluation of tumour promoting potency of fish borne toxaphene residues, as compared to technical toxaphene and UV-irradiated toxaphene.
- Author
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Besselink H, Nixon E, McHugh B, Rimkus G, Klungsøyr J, Leonards P, De Boer J, and Brouwer A
- Subjects
- Alanine Transaminase blood, Animals, Aspartate Aminotransferases blood, Body Weight drug effects, Carcinogens chemistry, Carcinogens radiation effects, Cell Communication drug effects, Gap Junctions drug effects, Glutathione Peroxidase metabolism, Insecticides chemistry, Insecticides radiation effects, Liver drug effects, Liver pathology, Liver Neoplasms chemically induced, Liver Neoplasms pathology, Organ Size drug effects, Rats, Tetrazolium Salts, Thiazoles, Thymus Gland drug effects, Toxaphene chemistry, Toxaphene radiation effects, Ultraviolet Rays, Carcinogens toxicity, Gadus morhua physiology, Insecticides toxicity, Meat analysis, Pesticide Residues toxicity, Toxaphene toxicity
- Abstract
In this study the potential impact of food chain-based biotransformation and physico-chemical weathering of toxaphene on its tumour promoting potential was investigated in vitro and in vivo. Human exposure to toxaphene is mainly through consumption of contaminated fish, therefore fish-borne residues of toxaphene (cod liver extract, CLE) were prepared by exposing cod to technical toxaphene (TT) for 63 days. UV-irradiated toxaphene (uvT) was included to represent a physico-chemical weathered toxaphene mixture. In vitro, TT, uvT and CLE all showed a dose- and time-dependent inhibition of gap junctional intercellular communication (GJIC) with a relative potency of CLE>TT=uvT. Tumour promoting potency was further studied in vivo in a medium term two-stage initiation/promotion bioassay in female Sprague-Dawley rats, using an increase in altered hepatic foci positive for glutathione-S-transferase-P (AHF-GST-P) as read out. No increase in AHF-GST-P occurred following exposure to either TT, uvT, or CLE, except for the positive control group (2,3,7,8-TCDD). Based on this study the no observed adverse effect level (NOAEL) for tumour promoting potency is at least 12.5mg/kg/week, or higher for CLE. Considering current human exposure levels in Europe it is doubtful that consumption of fish at current levels of toxaphene contamination give rise to human health risk.
- Published
- 2008
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