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 developed to describe these combinations, in which the nature of the nonideal effect combination may or may not be a function of the magnitude of predicted response (as opposed to only the proportions of the substances in a mixture). The approach is tested using data on rat carcinogenesis, drug action, and aquatic toxicity of pesticides. In the cases examined, the models predict substantial deviation from ideal behavior even under low doses.