Capacities of Membrane Lipids to Accumulate Neutral Organic Chemicals

Abstract

Lipids have been considered as the predominant components for bioaccumulation of organic chemicals. However, differences in accumulation properties between different types of lipid (e.g., storage and membrane lipids) have rarely been considered. Moreover, in view of toxic effects on organisms, chemical accumulation specifically in biological membranes is of particular importance. In this review article, partition coefficients of 240 neutral organic compounds between liposomes (phospholipid membrane vesicles) and water (K_lipw), reported in the literature or measured additionally for this work, were evaluated. Values of log K_lipw and log K_ow (octanol–water partition coefficients) differ by 0.4 on average. Polyparameter linear free energy relationships (PP-LFERs) can describe the log K_lipw data even better (standard deviations = 0.28–0.31) than the log K_ow model. Recent experimental data for highly hydrophobic compounds fit well to the PP-LFERs and do not indicate the existence of a previously postulated “hydrophobicity cutoff”. Predictive approaches based only on the molecular structure (KOWWIN, SPARC, COSMOthermX, COSMOmic) were also evaluated for K_lipw prediction. The PP-LFERs revealed that partition coefficients into membrane lipids can be two log units higher than those into storage lipids for H-bond donor compounds, suggesting that distinguishing between the two lipids is necessary to account for the bioaccumulation of these compounds, and that tissues rich in membrane lipids (e.g., kidneys, liver) instead of fat tissue can be the primary phase for accumulation.