Predicting bioconcentration factors of highly hydrophobic chemicals. Effects of molecular size

The bioconcentration factor (BCF) is a parameter that describes the ability of chemicals to concentrate in aquatic organisms. Traditionally, it is modeled by the log-log quantitative structure-activity relationship (QSAR) between the BCF and the octanol-water partition coefficient (K-ow). A significant scatter in the parabolic log(BCF)/log(K-ow) curve has been observed for narcotics with log(K-ow) greater than 5.5. This study shows that the scatter in the log(BCF)/log(K-ow) relationship for highly hydrophobic chemicals can be explained by the molecular size. The significance of the maximal cross-sectional diameter on bioconcentration was compared with the traditionally accepted effective diameter. A threshold value of about 1.5 nm for this parameter has been found to discriminate chemicals with log(BCF) > 3.3 from those with log(BCF) < 3.3. This critical value for the maximum diameter is comparable with the architecture of the cell membrane. This threshold is half thickness of leaflet constituting the lipid bilayer. The existence of a size threshold governing bioconcentration is an indication of a possible switch in the uptake mechanism from passive diffusion to facilitated diffusion or active transport. The value of the transition point can be used as an additional parameter to hydrophobicity for predicting BCF variation. The effect of molecular size on bioconcentration has been studied by accounting for conformational flexibility of molecules.