An analysis of the combined effects of organic toxicants.

This paper presents a basic database for the joint actions of 44 binary mixtures of various organic toxicants on Escherichia coli. The multiple toxicity behaviors observed from the E. coli organisms were analyzed and compared with previous works based on the Microtox tests. The two kinds of tests produced quite different responses, in terms of the joint action mode and the sum of toxic units, to various organic mixtures. However, detailed analyses with the considerations of the chemical's mechanisms of toxicity and the slope of toxicant's dose-response curve have revealed several general criteria for the prediction of combined effects of organic toxicants. First, for both reactive and non-reactive toxicants, either additive or less than additive (antagonistic) joint actions will be observed for chemicals of the same mechanism of toxicity. Second, the mixture of reactive toxicants with different mechanisms is the only category of organic mixtures associated with frequent observations of synergism. Third, greater-than-additive (synergistic) effects are inherently associated with toxicants having flat dose-response curves. Less than additive effects are, however, mainly related to a chemical's display steep dose-response curves. Model analyses indicate that the observed synergistic effects are due to response addition or response multiplication joint actions. Hence, most of the synergistic joint actions are non-interactive in nature and are governed by the dose-response relationships of individual toxicants.