MRA Toolbox v. 1.0: a web-based toolbox for predicting mixture toxicity of chemical substances in chemical products

Abstract

AbstractThe chemical risk assessment paradigm is shifting from “substance-based” to “product/mixture-based” and from “animal testing” to “alternative testing” under chemical regulations. Organisms and the environment may be exposed to mixtures rather than a single substance. Conducting toxicity tests for all possible combinations is impractical due to the enormous combinatorial complexity. This study highlights the development and application case studies of Mixture Risk Assessment Toolbox, a novel web-based platform that supports mixture risk assessment through the use of different prediction models and public databases. This integrated framework provides new functional values for assessors to easily screen and compare the toxicity of mixture products using different computational techniques and find strategic solutions to reduce the mixture toxicity in the product development process. The toolbox (https://www.mratoolbox.org) includes four additive toxicity models: two conventional (Concentration Addition; and Independent Action) and two advanced (Generalized Concentration Addition; and Quantitative Structure–Activity Relationship-based Two-Stage Prediction) models. We demonstrated the multiple functions of the toolbox using three cases: (i) how it can be used to calculate the mixture toxicity, (ii) those for which safety data sheet (SDS) only indicating representative toxicity values (EC50; and LC50), and (iii) those comprising chemicals with low toxic effects.