Tissue-Specific Accumulation, Depuration, and Transformation of Triphenyl Phosphate (TPHP) in Adult Zebrafish (<i>Danio rerio</i>)

Abstract

Understanding bioaccumulation and metabolism is critical for evaluating the fate and potential toxicity of compounds in vivo. We recently investigated, for the first time, the bioconcentration and tissue distribution of triphenyl phosphate (TPHP) and its main metabolites in selected tissues of adult zebrafish. To further confirm the metabolites, deuterated TPHP (d₁₅-TPHP) was used in the exposure experiments at an environmentally relevant level (20 μg/L) and at 1/10 LC₅₀ (100 μg/L). After 11-14 days of exposure to 100 μg/L of d₁₅-TPHP, the accumulation and excretion of d₁₅-TPHP reached equilibrium, at which point the intestine contained the highest d₁₅-TPHP (μg/g wet weight, ww) concentration (3.12 ± 0.43), followed by the gills (2.76 ± 0.12) > brain (2.58 ± 0.19) > liver (2.30 ± 0.34) ≫ muscle (0.53 ± 0.04). The major metabolite of d₁₅-TPHP, d₁₀-diphenyl phosphate (d₁₀-DPHP), was detected at significantly higher contents in the liver and intestine, at levels up to 3.0-3.5 times those of d₁₅-TPHP. The metabolic pathways of TPHP were elucidated, including hydrolysis, hydroxylation, and glucuronic acid conjugation after hydroxylation. Finally, a physiologically based toxicokinetic (PBTK) model was used to explore the key factors influencing the bioaccumulation of d₁₅-TPHP in zebrafish. These results provide important information for the understanding of the metabolism, disposition, and toxicology of TPHP in aquatic organisms.