title: A comparison of octanol-water partitioning between organic chemicals and their metabolites in mammals.
abstract: Bioaccumulation models take various elimination and uptake processes into account, estimating rates from chemical lipophilicity, expressed as the octanol-water partition ratio (K(ow)). Here, we focussed on metabolism, which transforms parent compounds into usually more polar metabolites, thus enhancing elimination. The aim of this study was to quantify the change in lipophilicity of relevant organic pollutants undergoing various biotransformation reactions in mammals. We considered oxidation reactions catalyzed by three enzyme groups: cytochrome P450 (CYP), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH). Estimated logK(ow) values of a selected dataset of parent compounds were compared with the logK(ow) of their first metabolites. The logK(ow) decreased by a factor that varies between 0 and -2, depending on the metabolic pathway. For reactions mediated by CYP, the decrease in K(ow) was one order of magnitude for hydroxylated and epoxidated compounds and two orders of magnitude for dihydroxylated and sulphoxidated xenobiotics. On the other hand, no significant change in lipophilicity was observed for compounds N-hydroxylated by CYP and for alcohols and aldehydes metabolized by ADH and ALDH. These trends could be anticipated by the calculus method of logK(ow). Yet, they were validated using experimental logK(ow) values, when available. These relationships estimate the extent to which the elimination of pollutants is increased by biotransformation. Thus, the quantification of the K(ow) reduction can be considered as a first necessary step in an alternative approach to anticipate biotransformation rates, which are hard to estimate with existing methods.
authors.affiliation: Radboud University Nijmegen, Institute for Wetland and Water Research, Department of Environmental Science, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands. a.pirovano@science.ru.nl
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pirovano
authors.forename: Nicolò
authors.initials: N
authors.lastname: Borile
authors.forename: A
authors.initials: A
authors.lastname: Jan Hendriks
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D055162:Biocatalysis; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008322:Mammals / Q000378:metabolism; D000442:Octanols / Q000737:chemistry*; D009930:Organic Chemicals / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D014867:Water / Q000737:chemistry*
chemical_list: D000442:Octanols; D009930:Organic Chemicals; D014867:Water; D003577:Cytochrome P-450 Enzyme System; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase