Novel aspects of uptake patterns, metabolite formation and toxicological responses in Salmon exposed to the organophosphate esters-Tris(2-butoxyethyl)- and tris(2-chloroethyl) phosphate

摘要

Given the compound differences between tris(2-butoxyethyl)- and tris(2-cloroethyl) phosphate (TBOEP and TCEP, respectively), we hypothesized that exposure of juvenile salmon to TBOEP and TCEP will produce compound-specific differences in uptake and bioaccumulation patterns, resulting in potential formation of OH-metabolites. Juvenile salmon were exposed to waterborne TCEP or TBOEP (0.04, 0.2 and 1 mg/L) for 7 days. The muscle accumulation was measured and bioconcentration factor (BCF) was calculated, showing that TCEP was less accumulative and resistant to metabolism in salmon than TBOEP. Metabolite formations were only detected in TBOEP-exposed fish, showing seven phase I biotransformation metabolites with hydroxylation, ether cleavage or combination of both reactions as important metabolic pathways. In vitro incubation of trout S9 liver fraction with TBOEP was performed showing that the generated metabolite patterns were similar to those found in muscle tissue exposed in vivo. However, another OH-TBOEP isomer and an unidentified metabolite not present in in vivo exposure were observed with the trout S9 incubation. Overall, some of the observed metabolic products were similar to those in a previous in vitro report using human liver microsomes and some metabolites were identified for the first time in the present study. Toxicological analysis indicated that TBOEP produced less effect, although it was taken up faster and accumulated more in fish muscle than TCEP. TCEP produced more severe toxicological responses in multiple fish organs. However, liver biotransformation responses did not parallel the metabolite formation observed in TBOEP-exposed fish.