Modeling mode of action of industrial chemicals: Application using chemicals on Canada's Domestic Substances List (DSL)

Abstract

Traditionally quantitative structure activity relationships (QSARs) are derived on the assumption that similar chemicals should behave in a toxicologically similar manner. The development of mechanistic models for acute toxicity requires the chemical classification to be based on similar mode of toxic action. Currently, the classification approaches used to predict the mode of toxic action are predominantly based on chemical fragments and, to a lesser extent, on their electronic properties. The discrete nature of the fragment-based approach, however, yields a classification that does not consider the electronic features of the entire chemical that has ªcontinuous characterº.The present study is based on the assumption that chemicals with the same mode of toxic action should possess commonality in their steric and electronic structure. The COmmon REactivity PAtterns (COREPA) approach has been applied to define the global physical properties and quantum-chemical descriptors best clustering chemicals according to their behavioural mode of action (MOA). The derived COREPA models for each mode were translated into decision trees and applied to screen the organic chemicals on Canadas Domestic Substances List (DSL) for their mode of toxic action. QSAR Comb. Sci. 22 (

Pharmaceuticals and Personal Care Products in the Environment: Regulatory Drivers and Research Needs

“…Possible environmentally-relevant modes of action and sensitive organisms for which QSARs could be developed are indicated in (Table 3 is a start), b) which species are at risk?, c) what is the effect on these species?, and d) based on this information develop new QSARs for these species and modes of action. A new approach to determine modes of action has recently been developed [62]. * Some researchers have highlighted the limitations of current standard ecotoxicity test methods and have recommended that a mode of action based approach be used [63].…”