Toxicokinetic patterns, metabolites formation and distribution in various tissues of the Chinese rare minnow (Gobiocypris rarus) exposed to tri(2‑butoxyethyl) phosphate (TBOEP) and tri-n-butyl phosphate (TNBP)

Abstract

Alkylated organophosphate esters (alkyl-OPEs) are widely used and extensively detected in aquatic organisms. This work investigated the tissue-specific toxicokinetics of two common alkyl-OPEs, tri(2‑butoxyethyl) phosphate (TBOEP) and tri‑n‑butyl phosphate (TNBP) in Chinese rare minnow (Gobiocypris rarus) through a 50 day uptake and depuration experiment. The tissue-specific bioconcentration factor (BCF) values for the two alkyl-OPEs ranged from 1 to 30 L/kg wet weight (ww), with the kidney and ovary as the tissues with the highest accumulation. The tissue BCFs only exhibited a significant correlation with lipid contents only in storage tissues (i.e., muscle, brain, ovary and testis), indicating that lipids might not be the major contributor to tissue distribution of TBOEP and TNBP. However, the contribution of blood perfusion and active transport to tissue-specific OPE accumulation needs to be further investigated. Lower accumulation of metabolites than parent chemicals was observed, with metabolite parent concentration factors (MPCFs) <1. Di-alkyl phosphate (DAP), bis(2‑butoxyethyl) phosphate (BBOEP) and di(n-butyl) phosphate (DNBP) were the most abundantly formed metabolites of TBOEP and TNBP in various tissues, followed by the monohydroxylated OPEs (OH-OPEs). However, bis(2‑butoxyethyl) hydroxyethyl phosphate (BBOEHEP), was detected at much lower levels in the tissues. All the investigated metabolites showed high production rates (kprod,metabolites) in the fish liver, followed by the GI tract and the kidney, indicating the importance of the hepatobiliary and urinary systems in eliminating the metabolites. Our study suggested that metabolism plays an important role in eliminating these two alkyl-OPEs in rare minnow and results in different tissue distribution mechanisms for metabolites and their compounds.