Protein and lipid binding parameters in rainbow trout (Oncorhynchus mykiss) blood and liver fractions to extrapolate from an in vitro metabolic degradation assay to in vivo bioaccumulation potential of hydrophobic organic chemicals

摘要: Binding of hydrophobic chemicals to colloids such as proteins or lipids is difficult measure using classical microdialysis methods due low aqueous concentrations, adsorption dialysis membranes and test vessels, slow kinetics equilibration. Here, we employed a three-phase partitioning system where silicone (polydimethylsiloxane, PDMS) serves third phase determine between water acts at the same time dosing device for chemicals. The applicability this method was demonstrated with bovine serum albumin (BSA). Measured binding constants (K(BSAw)) chlorpyrifos, methoxychlor, nonylphenol, pyrene were in good agreement an established quantitative structure-activity relationship (QSAR). A fifth compound, fluoxypyr-methyl-heptyl ester, excluded from analysis because apparent abiotic degradation. PDMS depletion then used partition coefficients rainbow trout (Oncorhynchus mykiss) liver S9 fractions (K(S9w)) blood plasma (K(bloodw)). K(S9w) K(bloodw) values consistent predictions obtained mass-balance model that employs octanol-water coefficient (K(ow)) surrogate lipid K(BSAw) represent protein binding. For each substantially greater than K(S9w), primarily contains more (1.84% wet weight vs 0.051%). parameters subsequently implemented vitro vivo extrapolation link metabolic degradation assay metabolism fish. Apparent volumes distribution (V(d)) calculated experimental data similar literature estimates. However, ratios (f(u)) relate clearance by intact 10 100 times lower previous modeling efforts. Bioconcentration factors (BCF) predicted higher earlier studies correlated poorly measured BCF One possible explanation finding bound can desorb rapidly thus contribute turnover This hypothesis remains be investigated future studies, ideally hydrophobicity.