Model-based description of distribution of chemicals in biosystems for the continuous dose.

The distribution of xenobiotics in a morphologically compartmentalised biosystem is described for the continuous dose of readily metabolised chemicals. The time hierarchy of individual processes the compounds undergo in the biosystem (transport-considered as uni-directional due to metabolism, protein binding, and metabolism) is used to simplify the model description. The explicit expressions for the steady-state concentrations (ci) in individual compartments as a function of transport rate constants and metabolism rate constants are derived. Further substantial simplification can be achieved if the phases of the test biosystem can be considered as approximately identical. Under the conditions ci can be used to calculate the explicit expressions for the average concentrations in all aqueous phases and in all membranes. The model parameters (the membrane/water partition coefficient, the water-to-membrane transport rate constant) are substituted by the reference (usually 1-octanol/water) partition coefficient using plausible mutual relationships. The dependences of the steady-state concentrations in individual compartments as well as the average quantities in all aqueous phases and in all membranes on hydrophobicity and on the metabolism rate constant are analysed in detail. The presented explicit expressions for the steady-state concentrations create a firm basis for: (1) derivation of model-based QSAR equations for toxicity caused by individual mechanisms of action and for further quantities of environmental interest like bioconcentration factors and total metabolism rates as well as for (2) scaling and comparison of QSAR equations among individual organisms.