QUANTITATIVE DESCRIPTION OF MIXTURE TOXICITY - EFFECT OF LEVEL OF RESPONSE ON INTERACTIONS

The simultaneous exposure of a biological system to a mixture of toxic substances may result in an ideal or nonideal combination of effects. In an extension of linear isobole theory, models are quantitatively d eveloped to describe these combinations, in which the nature of the no nideal effect combination may or may not be a function of the magnitud e of predicted response (as opposed to only the proportions of the sub stances in a mixture). The approach is tested using data on rat carcin ogenesis, drug action, and aquatic toxicity of pesticides. In the case s examined, the models predict substantial deviation from ideal behavi or even under low doses.