A rule-based method for comprehensive risk assessment of the mutagenic potential of drugs

TOXI 36

Catrin Hasselgren Arnby, catrin.hasselgren-arnby@astrazeneca.com1, Lars Carlsson2, Claire Gavaghan, claire.gavaghan@astrazeneca.com2, and Scott Boyer, scott.boyer@astrazeneca.com2. (1) Safety Assessment, AstraZeneca, Pepparedsleden 1, 43183 Mölndal, Sweden, (2) Safety Assessment, AstraZeneca R&D Mölndal, Pepparedsleden 1, 43183 Mölndal, Sweden
We have developed a comprehensive system for assessing mutagenic potential of new compounds. The system is built on Ames data from public sources such as NTP, as well as our internal data and the database comprises ~7000 compounds. Any molecule submitted to the system is passed through a series of steps and the output lists i) structural near neighbours with experimental results ii) alerting substructures iii) consensus QSAR results consisting of three different QSAR models. A set of rules that aid interpretation of the output and enhance the overall predictive performance has been derived. The system provides a more complete picture of the information available when doing risk assessment of new compounds and allows a more realistic view of the underlying data. Using only QSAR predictions, accuracy ranges from 85-90%. The confidence for an individual prediction varies depending on additional output and gives an overall confidence index for each prediction.
 

Poster Session and Awards
6:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- 204 A/B, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Division of Chemical Toxicology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007