Evaluation of QSAR Models for the Prediction of Ames Genotoxicity: A Retrospective Exercise on the Chemical Substances Registered Under the EU REACH Regulation

We evaluated the performance of seven freely available quantitative structure-activity relationship models predicting Ames genotoxicity thanks to a dataset of chemicals that were registered under the EU Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation. The performance of the models was estimated according to Cooper's statistics and Matthew's Correlation Coefficients (MCC). The Benigni/Bossa rule base originally implemented in Toxtree and re-implemented within the Virtual models for property Evaluation of chemicals within a Global Architecture (VEGA) platform displayed the best performance (accuracy = 92%, sensitivity = 83%, specificity = 93%, MCC = 0.68) indicating that this rule base provides a reliable tool for the identification of genotoxic chemicals. Finally, we elaborated a consensus model that outperformed the accuracy of the individual models.     

The vitamin k-antagonism of salicylate and warfarin

When administered in high dosages, salicylate acts as a vitamin K-antagonist: it induces a decrease of the plasma concentration of the Gla-containing coagulation factors and an accumulation of microsomal substrates for vitamin K-dependent carboxylase in the liver and in the lung. In vitro the drugs inhibit the DTT-dependent reductases which mediate the reduction of vitamin K epoxide and vitamin K quinone. NADH-dependent reductase and vitamin K-dependent carboxylase are not inhibited.