New methods of top-to-down mixture toxicity prediction: A case study of eliminating of the effects of cosolvent from binary mixtures.

At present, the toxicity prediction of mixtures mainly focuses on the concentration addition (CA) and independent action (IA) based on individual toxicants to predict the toxicity of multicomponent mixtures. This process of predicting the toxicity of multicomponent mixtures based on single substances or low component mixtures is called down-to-top method in this study. However, due to the particularity of some toxicants, we have to use the top-to-down idea to obtain or eliminate the toxicity of some components from mixtures. For example, the toxicity of toxicants is obtained from the toxicity of a mixture with, especially toxic, cosolvent added. In the study, two top-to-down methods, the inverse CA (ICA) and inverse IA (IIA) models, were proposed to eliminate the effects of a certain component from multicomponent mixtures. Furthermore, taking the eight binary mixtures consisting of different shapes of cosolvents (isopropyl alcohol (IPA) having hormesis and dimethyl sulfoxide (DMSO)) and toxicants (two ionic liquids and two pesticides) as an example, combined with the interaction evaluated by CA and IA model, the influence of different shapes of components on top-to-down toxicity prediction was explored. The results showed that cosolvent IPA having hormesis may cause unpredictable effects, even at low concentrations, and should be used with caution. For DMSO, most of the toxicant's toxicity obtained by ICA and IIA models were almost in accordance with those observed experimentally, which showed that ICA and IIA could effectively eliminate the effects of cosolvent, even if toxic cosolvent, from the mixture. Ultimately, a frame of cosolvent use and toxicity correction for the hydrophobic toxicant were suggested based on the top-to-down toxicity prediction method. The proposed methods improve the existing framework of mixture toxicity prediction and provide a new idea for mixture toxicity evaluation and risk assessment.