Evaluation of tumour promoting potency of fish borne toxaphene residues, as compared to technical toxaphene and UV-irradiated toxaphene.
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.
Besselink
H
H
BioDetection Systems BV, Kruislaan 406, 1098 SM, Amsterdam, The Netherlands. harrie.besselink@bds.nl
Nixon
E
E
McHugh
B
B
Rimkus
G
G
Klungsøyr
J
J
Leonards
P
P
De Boer
J
J
Brouwer
A
A
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D002450:Cell Communication / Q000187:drug effects; D048389:Gadus morhua / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D007306:Insecticides / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology; D008460:Meat / Q000032:analysis*; D009929:Organ Size / Q000187:drug effects; D010573:Pesticide Residues / Q000633:toxicity*; D051381:Rats; D013778:Tetrazolium Salts; D013844:Thiazoles; D013950:Thymus Gland / Q000187:drug effects; D014112:Toxaphene / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D014466:Ultraviolet Rays
D002273:Carcinogens; D007306:Insecticides; D010573:Pesticide Residues; D013778:Tetrazolium Salts; D013844:Thiazoles; D014112:Toxaphene; D005979:Glutathione Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C022616:thiazolyl blue