ASSESSMENT OF THE COMBINED EFFECTS OF SUBSTANCES - THE RELATIONSHIP BETWEEN CONCENTRATION ADDITION AND INDEPENDENT ACTION

The assessment of the combined effects of substances is usually based on one of two different concepts: concentration addition or independen t action. Both concepts are founded on different pharmacological assum ptions about sites and modes of actions of substances, but in toxicolo gy and ecotoxicology such knowledge is rare for most chemicals. In ord er to validate experimental results and to allow for precautious asses sments, the quantitative relationships between concentration addition and independent action are therefore of interest. In this paper, we de rive for the Weibull, the logistic, and the normal distribution functi ons the concentrations where the response probability due to concentra tion addition exceeds that due to independent action and vice versa. T his is done (a) by analytically comparing both models for low and high mixture concentrations and (b) by numerically calculating the respons e probabilities when concentration addition and independent action agr ee. It is shown that the relationships between the models for joint ac tion depend on the distribution functions, the corresponding slope par ameters, and on the mixture concentrations administered.