Application of in silico and in vitro methods in the development of adverse outcome pathway constructs in wildlife

Abstract

There is a long history of using both in silico and in vitro methods to predict adverse effects in humans and environmental species where toxicity data are lacking. Currently, there is a great deal of interest in applying these methods to the development of so-called 'adverse outcome pathway' (AOP) constructs. The AOP approach provides a framework for organizing information at the chemical and biological level, allowing evidence from both in silico and in vitro studies to be rationally combined to fill gaps in knowledge concerning toxicological events. Fundamental to this new paradigm is a greater understanding of the mechanisms of toxicity and, in particular, where these mechanisms may be conserved across taxa, such as between model animals and related wild species. This presents an opportunity to make predictions across diverse species, where empirical data are unlikely to become available as is the case for most species of wildlife.

Keywords: adverse outcome pathway; in silico modelling; in vitro techniques; predictive toxicology.

Figure 1.

Representation of the key features of a ‘source to outcome’ and ‘AOP’. (Online version in colour.)

Figure 2.

Binding of an electrophile to a nucleophilic group of a protein demonstrating that the same MIE can result in different toxicities in different species.