Algal toxicity of nitrobenzenes: combined effect analysis as a pharmacological probe for similar modes of interaction.

An analysis regarding the effects of the mixture toxicity of different nitrobenzenes on the reproduction of the green alga Scenedesmus vacuolatus was undertaken using the concepts of concentration addition and response addition. Using lipophilicity-based quantitative structure-activity relationship (QSAR) modeling for nitrobenzenes, the assumption is held that mononitrobenzenes may exert narcotic effects as a common type of action, whereas dinitrobenzenes show a somewhat greater toxicity. From the literature, QSARs based on quantum chemical parameters suggest that some mononitrobenzenes may be effective through additional other modes of action. The toxicity of a mixture of 14 nitrobenzenes clearly exceeds the predicted combined effects, as expected for the sum of toxic units from a uniform narcotic mode of action. Moreover, the observed combined effect is smaller than that predicted from similarly acting compounds calculated on the basis of the parameterized dose-response functions using concentration addition. Further modeling of the combined effect, joining the models of concentration addition for components with anticipated similar modes of action and of response addition for those with independent action, led us to propose that not all nitrobenzenes follow the same mode of action. This idea is in line with the hypothesis derived from quantum chemical QSAR considerations. Most interestingly, the methodology introduced here uses combined effect analysis as a pharmacological probe to test for similarity in the mode of action of mixture components.