TY - JOUR
T1 - Evaluation of tumour promoting potency of fish borne toxaphene residues as compared to technical toxaphene and uv-irradiated toxaphene
AU - Besselink, H.T.
AU - Nixon, E.
AU - McHugh, B.
AU - Rimkus, G.
AU - Klungsoyr, J.
AU - Leonards, P.E.G.
AU - de Boer, J.
AU - Brouwer, A.
PY - 2008
Y1 - 2008
N2 - 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 12.5 mg/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. © 2008 Elsevier Ltd. All rights reserved.
AB - 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 12.5 mg/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. © 2008 Elsevier Ltd. All rights reserved.
U2 - 10.1016/j.fct.2008.04.039
DO - 10.1016/j.fct.2008.04.039
M3 - Article
SN - 0278-6915
VL - 46
SP - 2629
EP - 2638
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
IS - 8
ER -