Hepatic retention and toxicological responses during feeding and depuration periods in Atlantic salmon ( Salmo salar ) fed graded levels of the synthetic antioxidant, butylated hydroxytoluene.

The human safety aspects of seafood production require the expansion of vital knowledge of both nutrients and possible contaminants along the entire production chain. Thus, production of safer seafood can be achieved by using feed materials that are low in contaminants, while maintaining balanced nutrition, in order to secure optimal fish and consumer health. Our understanding of primary responses of fish health and production related diseases, as well as biological processes that influence carry-over and lowering of contaminants in farmed fish, will contribute to a sustainable production of safer seafood products. Therefore, we have studied the liver deposition and toxicological effects in salmon fed graded levels of BHT during a 12-week feeding followed by a 2-week depuration period using chemical, molecular, and catalytic assays. In general, our data showed that BHT was significantly retained in the liver and selectively modulated toxicological responses in the xenobiotic biotransformation pathways during the feeding period. Specifically, BHT produced consistent dose- and time-specific gene expression patterns for AhR2alpha, AhR2beta, CYP1A1, CYP3A, UGT1, and GSTpi. The effect of BHT on the gene expression of biotransformation enzyme did not parallel enzyme activity levels, suggesting a possible inhibition by parent BHT or its metabolites. As a safety precaution, the production of farmed Atlantic salmon in Norway requires a mandatory 2-week depuration period prior to slaughtering and market delivery to ensure the elimination of veterinary medicaments, additives, and other undesirable components. Comparison of feeding and depuration periods showed that BHT was highly retained in fish liver, as only 8-13% of fed BHT was eliminated during the 2-week depuration period. This is just a part of the total concentration in the whole fish, since BHT may have been distributed and accumulated in other organs. Since BHT or its metabolites putatively inhibited biotransformation enzymes and affected metabolism of the compound, they may have potential for toxicological and adverse health effects for both fish and fish consumers through carry-over processes from the fish products.