Quantitative structure-toxicity relationship model for acute toxicity of organophosphates via multiple administration routes in rats and mice.

• We predicted the acute toxicity of organophosphates based on chemical structure. • Large data were collected to develop quantitative structure-toxicity relationship models. • The random forest algorithm was used to develop these models. • Acute toxicity data from different administration routes could not be combined. • QSTR models achieve high predictive performance despite large variance in datasets. Organophosphates (OPs) are highly toxic compounds, with widespread application in agricultural and chemical industries, whose introduction into the environment poses serious hazards to humans and ecological systems. To assess and ultimately mitigate these hazards, this study predicted the acute toxicity of OPs according to their chemical structure and administration route. The acute toxicity data of 161 OPs in two species via six different administration routes were manually collected and used to develop a series of quantitative structure–toxicity relationship (QSTR) models with robust and practical predictive abilities. The random forest algorithm was used to develop the models, employing both quantum chemical and two-dimensional descriptors according to OECD guidelines. Correlation results and feature similarities indicated that whereas acute toxicity data from rats and mice via the same administration route were combinable for modeling, data from different routes were not. Six QSTR models for each route in a single species and two QSTR models for a single route in the two species were constructed, achieving practical predictive performance. Despite significant variances in their datasets, the prediction models could predict the acute toxicity of novel or unknown OPs, realize rapid assessment, and provide guidance for regulatory decisions to reduce the hazards of OPs. [ABSTRACT FROM AUTHOR]