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.
BioDetection Systems BV, Kruislaan 406, 1098 SM, Amsterdam, The Netherlands. harrie.besselink@bds.nl
H
H
Besselink
E
E
Nixon
B
B
McHugh
G
G
Rimkus
J
J
Klungsøyr
P
P
Leonards
J
J
De Boer
A
A
Brouwer
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