Strategic Design of Alternative Methods to Reduce Animal Testing

The success of the Knoxville Reactive Toxicity Workshops in relating intermediate empirical measures of chemical reactivity to the downstream biological effects (see Conceptual Framework Manuscript) has paved the way for research to compute the intermediate measures of reactivity directly from structure. The IQF framework will show that important endpoints such as rodent or fish inhalation toxicity can be directly related to the KGSH which the reaction half-life under reference conditions, in much the same way Log P is used to predict bioconcentration factors and related transport properties. CLOGP is a computer program to calculate Log P for chemical, and the Athens Workshop was convened to explore ways of predicting Log GSH directly from structure.

Using SPARC technology (link to SPARC website), the authors of the free website for SPARC at the University of Georgia and U.S. EPA outlined an approach to build a model for chemicals which react with thiol moieties via the Michael addition mechanism as a proof-of-concept. Furthermore, the workshop kicked-off the planning for a larger workshop in molecular modelling for reactivity.

CATABOL is QSAR approach to modelling the biodegradability of chemicals by mixed microbial populations, and to identify potential degradation products. Although a microbial test for ready-degradation does not involve animal tests, microbial degradation is an important parameter in setting priorities for further testing in many countries. In the process called PBT analysis, the chemical is evaluated for Persistence, Bioaccumulation and Toxicity in that order; and having a reliable CATABOL to eliminate the readily degradable chemicals from further testing is important. Moreover, environmental regulations in several countries require further testing if a stable degradation product is formed. Since CATABOL has the capability of predicting both pieces of information, IQF hosted a workshop of regulators and experts from industry and academia to conduct a peer consultation of CATABOL.

Catabol Agenda 95KB

Panelists from the workshop 102KB

Consultation report and slides will be available online soon.
For further information on Catabol click here

The 1st Knoxville workshop in 2005 accomplished a major IQF goal by formulating a conceptual framework for predicting reactive toxicity. At the heart of the conceptual framework is the use of model compounds which simulate natural proteins and other important cellular targets for reactive chemicals and produce a reactivity profile. These model compounds are easily synthesized and react with chemicals in a test tube, so measuring chemical reactivity does not have to involve any animals or cells.

List of Attendees 78KB