Tissue-Specific Accumulation, Biotransformation, And Physiologically Based Toxicokinetic Modeling Of Benzotriazole Ultraviolet Stabilizers In Zebrafish (Danio Rerio)

Benzotriazole ultraviolet stabilizers (BUVSs) are high-production-volume chemicals with ubiquitous occurrence in the aquatic environment. However, little is known about their bioconcentration and biotransformation, and physiologically based toxicokinetic (PBTK) models for BUVSs are lacking. This study selected six BUVSs for which experiments were performed with zebrafish (Danio rerio) exposed to two different levels (0.5 and 10 mu g.L-1). Higher kinetic bioconcentration factors (BCFs) were observed at the lower exposure level with environmental relevance, with BCF of 3.33 x 10(3) L.kg(-1) for 2-(2-hydroxy-3,5-di-tertbutylphenyl)-5-chlorobenzotriazole (UV-327). This phenomenon was interpreted by a nonlinear adsorption mechanism, where binding with specific protein sites contributes to bioconcentration. Muscle exhibited the lowest accumulation, in which depuration half-life of UV-327 was 19.5 d. In kidney, muscle, ovary, gill, and skin, logBCF increased with increase in log K-OW of the BUVSs until log K-OW was ca. 6.5, above which logBCF decreased. However, the trend was not observed in the liver and intestine. Six biotransformation products were identified and mainly accumulated in the liver and intestine. Considering the nonlinear adsorption mechanism in the PBTK model, the prediction accuracy of the model was improved, highlighting the binding of xenobiotics with specific protein sites in assessing the bioconcentration of chemicals for their risk assessment.