title: 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.
authors.affiliation: Department of Analytical Environmental Chemistry, UFZ-Helmholtz Centre for Environmental Research, Permoserstrasse 15, D-04318 Leipzig, Germany.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Endo
authors.forename: Trevor N
authors.initials: TN
authors.lastname: Brown
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Goss
mesh_terms: D008962:Models, Theoretical; D009930:Organic Chemicals / Q000737:chemistry*
chemical_list: D009930:Organic Chemicals