The ABCG2 protein in vitro transports the xenobiotic thiabendazole and increases the appearance of its residues in milk

Abstract

[EN] Thiabendazole (2–(4–thiazolyl)benzimidazole, TBZ) is a broad–spectrum anthelmintic widely used in humans and cattle. It is also used as post–harvest agricultural fungicide, thus preserving crop quality and marketability (Hajikhani et al., 2024). Adverse effects after TBZ exposure including endocrine, nephrogenic, hepatogenic, teratogenic and neurological effects have been reported in mammals (Ekman et al., 2014). Etiological factors behind TBZ toxicity remain ambiguous; however, it has been hypothesized that it may be due to its bioactivation to 5OH–TBZ by the cytochrome P450 1A2 (CYP1A2) (Coulet et al., 1998a; Jamieson et al., 2011) (Fig. 1). Therefore, National and International Food Safety Authorities have established regulations for the usage of TBZ on food products setting maximum residue limits (MRLs) for the sum of TBZ and its metabolites in both agricultural and animal products ranging from 0.01 to 7 mg/kg depending on the product (European Food Safety Authority (EFSA) et al., 2021; U.S. Food and Drug Administration (FDA), 2021). Unfortunately, MRLs derived from pesticide use are equal to or higher than veterinary MRLs for all commodities, and the possible aggregated exposure from TBZ residues has not been studied, making it impossible to rule out an overexposure to TBZ through the food chain.