Strategic Design of Alternative Methods to Reduce Animal Testing

The International QSAR Foundation has invited a number of international experts from the European Union, Canada, and the USA to a retreat at Utah State University in Logan, Utah to evaluate the use of model nucleophiles as an organizing principle for predicting the many adverse effects of reactive chemicals. Predicting the effects of chemicals involves the prediction of molecular interactions with biological systems as well as the biological consequences of those interactions.  Reactive chemicals form covalent bonds with macromolecules which increases the potency of chemicals as well as the spectrum of long-term effects.  Chemicals that selectively bind to thiol groups in proteins commonly impact the immune system which is observed as skin and lung sensitization as well as delayed organ failure.  Our framework suggests that if the reaction rates of chemicals toward model nucleophiles such as glutathione and lysine can be predicted, the reaction rates will correlate with endpoints used to assess skin sensitization, inhalation toxicity, hepatocyte toxicity and aquatic toxicity.