General Model for Estimating Partition Coefficients to Organisms and Their Tissues Using the Biological Compositions and Polyparameter Linear Free Energy Relationships

Abstract

Equilibrium partition coefficients of organic chemicals from water to an organism or its tissues are typically estimated by using the total lipid content in combination with the octanol-water partition coefficient (K(ow)). This estimation method can cause systematic errors if (1) different lipid types have different sorptive capacities, (2) nonlipid components such as proteins have a significant contribution, and/or (3) K(ow) is not a suitable descriptor. As an alternative, this study proposes a more general model that uses detailed organism and tissue compositions (i.e., contents of storage lipid, membrane lipid, albumin, other proteins, and water) and polyparameter linear free energy relationships (PP-LFERs). The values calculated by the established PP-LFER-composition-based model agree well with experimental in vitro partition coefficients and in vivo steady-state concentration ratios from the literature with a root mean squared error of 0.32-0.53 log units, without any additional fitting. This model estimates a high contribution of the protein fraction to the overall tissue sorptive capacity in lean tissues (e.g., muscle), in particular for H-bond donor polar compounds. Direct model comparison revealed that the simple lipid-octanol model still calculates many tissue-water partition coefficients within 1 log unit of those calculated by the PP-LFER-composition-based model. Thus, the lipid-octanol model can be used as an order-of-magnitude approximation, for example, for multimedia fate modeling, but may not be suitable for more accurate predictions. Storage lipid-rich phases (e.g., adipose, milk) are prone to particularly large systematic errors. The new model provides useful implications for validity of lipid-normalization of concentrations in organisms, interpretation of biomonitoring results, and assessment of toxicity.

Critical Review and Interpretation of Environmental Data for Volatile Methylsiloxanes: Partition Properties

“…63 Therefore, it is necessary to consider how differences in lipid types might influence VMS partitioning into, and distribution within, biota. Endo and coworkers have quantified the differences in solvation characteristics of membrane lipids and storage lipids.…”

QSARs for aquatic toxicity: celebrating, extending and displaying the pioneering contributions of Ferguson, Konemann and Veith

“…An example of such an application is the gas and liquid phase adsorption of organic species onto activated carbon [42]. Abraham solvation parameters are increasingly used to estimate partition coefficients, especially for heterogeneous phases of uncertain composition [43]. An appealing and successful application has been to relate these parameters directly to toxicity as demonstrated by McGrath and colleagues [44].…”

Importance of lipid analysis and implications for bioaccumulation metrics

“…For purposes of modeling and predicting bioaccumulative potential of a hydrophobic chemical, the accumulation capacity of “lipid” (i.e., the fugacity capacity; Z lipid ) is generally assumed to be equal to that of n ‐octanol ( Z octanol ) and the lipid‐octanol partition coefficient ( K lipid/octanol = Z lipid / Z octanol ) equal to 1.0. When quantitatively described using linear solvation energy relationships (LSER), the solute–solvent interactions of octanol, membrane lipids, and storage lipids can all be differentiated (Endo et al ). Theoretical partition coefficients between octanol and both membrane and storage lipids ( K lipid/octanol ) for representative compounds from several different chemical classes are shown in Fig.…”

“…Comparison of theoretical log K lipid/octanol values for different chemical classes, calculated from equations found in Endo et al (). Solid and hatched bars represent membrane and storage lipids, respectively.…”