Octanol: water partition coefficients mixture toxicities

Common unspecific mode of action of all organic compounds has been taken up in quantitative structure-activity relationships (QSARs see Chapter 5) as the concept of baseline toxicity and in toxicokinetics as the body burden concept (see Chapter 2). Baseline toxicity refers to the idea that a minimum toxicity expectation may be formulated for any given organic compound based on considerations of a compound s partition properties between hydrophilic and lipophilic chemicals (e.g., between water and octanol). Commonly, this is expressed in terms of the octanol-water partition coefficient (K0,J of a chemical. The partition coefficient allows estimations of a local concentration or body burden for each individual chemical in the mixture. Assuming that this produces the same toxic effect (disturbances of cell membranes), it is then possible to anticipate joint narcotic action by adding together the respective local concentrations or body burdens for each individual mixture component. 

In almost all of the studies presented here (as well as in most others not reported here) the chemical mixtures that produced unanticipated toxic effects contained at least one lipophile (K > 2.00) and one hydrophile ( CW < 2.00). The octanol water partition coefficients (7T w) are given in parentheses for each of the chemicals identified to point out the lipophilic and hydrophilic species. 

Traditional toxicology addresses the toxic effects of single chemicals and even some of the mixture effects (additivity, potentiation, and synergism) weU, but it is unable to account for some observed effects of chemical mixtures. These unexplained effects often ensue when exposures are to mixtures of hpophilic and hydrophihc chemicals. Octanol water partition coefficients serve to predict the lipophilic or hydrophihc nature of chemical compounds. 

In the context of drug-like substances, hydrophobicity is related to absorption, bioavailability, hydrophobic drug-receptor interactions, metabolism and toxicity. Closely related to log P is the octanol-water distribution coefficient (logDpn), accounting for partition of pH-dependent mixture of ionizable species. Ionization of any compound makes it more water soluble and then less lipophilic. The log D can be calculated from log Pand acid dissociation constant pJC, by the following expression [Cronin, Aptula et al, 2002b Livingstone, 2003] ... 

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