Tissue distribution, accumulation, and biotransformation of butylated hydroxytoluene in adult zebrafish (Danio rerio)

As a widely used synthetic phenolic antioxidant (SPA), butylated hydroxytoluene (BHT) has been frequently detected in aquatic ecosystem. In organisms, BHT undergoes species-dependent biotransformation which can influence its toxicity. Despite data on its metabolism in mammals, tissue-specific distribution and bioaccumulation of BHT and its metabolites in fish remain unclear. In this study, adult zebrafish were exposed to 0.1 and 1 μM BHT for 21 days, followed by a 7-day depuration. BHT was rapidly degraded more than 50% within one day in the exposure solution, and BHT-OH was identified as the most abundant metabolite excreted from zebrafish. The highest concentration of BHT were observed in the liver and ovary with kinetic bioconcentration factors (BCF k ) over 2000 L/kg. However, the depuration half-life of BHT in different tissues was relatively short, ranging from 0.89 to 3.15 days. In contrast to the bioconcentration pattern of BHT, its metabolites were preferentially distributed in plasma due to their higher affinity to apolipoprotein A-I. BHT-CHO and BHT-Q were the dominant metabolites that readily accumulated in liver and brain, while BHT-COOH tended to deposit in the brain and ovary at high dose (1 μM) group. Compared with BHT, these toxic metabolites have a higher persistent potential in biological tissues. Our findings underscore the significance of considering the biotransformation in the toxic assessment of BHT congeners. • BHT is readily transformed to BHT-OH in both water and zebrafish. • BHT tend to accumulate in fish liver and ovary with BCF over 2000 L/kg. • BHT-CHO and BHT-Q are the dominant metabolites that accumulate in zebrafish. • BHT metabolites exert higher affinity to plasma apolipoprotein A-I than BHT.