Using Various Nonlinear Response Surfaces for Mathematical Description of the Type of Combined Toxicity

Dose Response. 2018 Dec 5;16(4):1559325818816596. doi: 10.1177/1559325818816596. eCollection 2018 Oct-Dec.

Abstract

The article considers the problem of characterizing the type of combined action produced by a mixture of toxic substances with the help of nonlinear response functions. Most attention is given to second-order models: the linear model with a cross-term and the quadratic model. General propositions are formulated based on the data on combined toxicity patterns previously obtained by the Ekaterinburg nanotoxicology team in animal experiments and analyzed with the help of the linear model with a cross-term. It is shown now that the quadratic model features these general characteristics in full measure, but interpretation of combined toxicity types based on isobolograms obtained by the quadratic model is more difficult. This suggests that where both models ensure a comparable quality of combined toxicity type identification, it would be enough to use the linear model with a cross-term.

Keywords: combined toxicity; isobolograms; nonlinearity; response surface methodology.