Comparison of Individual Dose-Response Curves

Comparison of dose-response curves of one chemical (A) in the absence and presence of a second chemical (B) has been proposed as a tool to predict whether the combined action of the two chemicals is either additive or independent (Cassee et al. 1998). 

In the case of dose additivity, the dose-response curve of A is determined on a linear- or log-dose scale, and an equi-effective dose of A (liA.equi) and B d resulting in the same effect is estimated. Using the fixed dose d of chemical B and adding various doses dp - i A.equi) of A, the dose-response curve should shift to the left and reach the same maximum as the maximum for the dose-response curve of A alone when the effect of B is smaller than Amax- However, in case of competitive agonism, the effect of B does not affect the effect of A -f B at higher dose of A. 

In the case of an independent effect, the addition of a fixed dose of B will produce an upward shifted dose-response curve. An independent effect can be calculated from the equation 

This method is based on the idea of response addition and was developed to accommodate the observation that compounds may act on different subsystems within an organism, which may well involve different sites and modes of action. Individual mixture components are not assumed to contribute to the overall mixture effect if they are present at subthreshold levels. 

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