Two-stage prediction of the effects of imidazolium and pyridinium ionic liquid mixtures on luciferase.

Hui-Lin Ge,Shu-Shen Liu,Xiang-Wei Zhu,Bing-Xia Su

doi:10.3390/molecules19056877

Hui-Lin Ge, Shu-Shen Liu + Show 2 more

Open Access

https://doi.org/10.3390/molecules19056877

Copy DOI

Abstract

The predicted toxicity of mixtures of imidazolium and pyridinium ionic liquids (ILs) in the ratios of their EC50, EC10, and NOEC (no observed effect concentration) were compared to the observed toxicity of these mixtures on luciferase. The toxicities of EC50 ratio mixture can be effectively predicted by two-stage prediction (TSP) method, but were overestimated by the concentration addition (CA) model and underestimated by the independent action (IA) model. The toxicities of EC10 ratio mixtures can be basically predicted by TSP and CA, but were underestimated by IA. The toxicities of NOEC ratio mixtures can be predicted by TSP and CA in a certain concentration range, but were underestimated by IA. Our results support the use of TSP as a default approach for predicting the combined effect of different types of ILs at the molecular level. In addition, mixtures of ILs mixed at NOEC and EC10 could cause significant effects of 64.1% and 97.7%, respectively. Therefore, we should pay high attention to the combined effects in mixture risk assessment.

Highlights

Organisms are usually exposed to pollutant mixtures in the environment [1]
Important questions are: (i) can their mixture toxicities be predicted by concentration addition (CA), independent action (IA) or two-stage prediction (TSP); (ii) what is the type of their toxic interaction; and (iii) what is the location relationship among the concentration–response curves (CRCs) predicted by CA, IA, and TSP for their mixtures? some of these issues have been preliminarily investigated in single types of Ionic liquids (ILs) such as imidazolium ILs, it is necessary to further explore and validate this for mixtures of different types of ILs
EPrd − EObs where n is the number of mixture components, ci is the concentration of the ith component in the mixture, Fi −1 is the inverse of function describing the CRC of the ith component, Emix,CA is mixture effect predicted by CA, Emix,IA is mixture effect predicted by IA, Ei is the effect of the ith component in a mixture, EPrd is the effect predicted by a reference model, and EObs is the effect observed

Summary

Introduction

Organisms are usually exposed to pollutant mixtures in the environment [1]. The assessment and prediction of mixture effects is generally based on two additive reference models: concentration addition (CA) and independent action (IA). Imidazolium ILs can cause multiple toxic interactions (addition, synergism, and antagonism) in different composition and concentration ranges [19]. Little is known about the combined toxicity of different types of ILs, including imidazolium and pyridimium ILs. Important questions are: (i) can their mixture toxicities be predicted by CA, IA or TSP; (ii) what is the type of their toxic interaction (addition, synergism or antagonism); and (iii) what is the location relationship among the concentration–response curves (CRCs) predicted by CA, IA, and TSP for their mixtures? Based on the luciferase toxicity test, we demonstrated that the effects of mixtures of ten ILs with J-shaped CRC can be predicted by the CA model [23]. Mixture effects of ILs in the ratios of their EC50, EC10, and NOEC on luciferase were tested based on microplate toxicity analysis. Combined effects were evaluated by comparing the predicted effects by CA, IA, and TSP to the observed effects of these mixtures

Single Toxicity

Mixture Toxicity

Chemicals

Luciferase Toxicity Test

Experimental Design and Toxicity Prediction of Mixtures

Conclusions