Rapid response toxicology prediction platform

Project Summary Abstract In silico toxicology is an important alternative approach to animal testing that provides a fast and inexpensive prediction of toxicityIt uses computer models to predict whether a chemical is safe or if there is a potential hazardIn silico methods are particularly valuable when a decision needs to be made quicklysuch as for an emergency response to a chemical spill or when there is little or no test material available such as for an assessment of metabolitesUnfortunatelythere are a number of obstacles to performing such analysesAlthough running the models is fastthe whole process of making predictionsincluding selecting and acquiring the modelsinterpreting the resultsperforming an expert reviewand documenting the resultscan be time consumingIt is also difficult to defend the resultsprimarily due to a lack of published procedures for performing an in silico assessmentTo support the development of such protocolsamember international cross industry consortium has been assembledThis consortium is led by Leadscope and includes representatives from international regulatory agencies and government research laboratories in the United StatesCanadaJapan and Europeas well as large companies from various industrial sectors e gpharmaceuticalfoodcosmeticsagrochemicalsacademic groups and other stakeholdersThis consortium will publish in silico protocols for seven major toxicological endpointsskin respiratory oral sensitizationrepeated dose toxicitycarcinogenicityreproductive and developmental toxicityendocrine activity and disruptorsliver toxicity andpersistencebioaccumulation and environmental toxicityThe protocols will ensure any in silico assessments are performed in a consistentrepeatablewell documented and defendable mannerThis proposal also outlines the development of a first to market software platform LeadscopeRapid Response that will make toxicity assessments based upon these generally accepted and published protocolsFor each major endpointa five step methodology for incorporating assessments into the rapid response platform is outlinedThis process starts with the development and publication of the protocolAn exercise to understand the structure activity relationships SAR across public and proprietary databases will be initiatedwithout revealing any confidential informationA specialized database containing the necessary information on specific studiesas defined in the protocolswill be createdThis database and SAR knowledge are then used to build and enhance different computational methodologies and these models and decision frameworksas outlined in the published protocolswill be integrated into the platformThe platform will be commercialized and made available broadly at a low annual costwith separate subscription licensing of the modelsdatabases and other tools for integration of proprietary data and knowledgeThere will also be a pay as you go pricing option to ensure access for smaller organizationsThe successful deployment of this technology provides a significant commercial opportunity for Leadscope Incand will support increased productivity for those companies involved in chemical research and development e gpharmaceutical companiesagrochemical companiescosmeticsindustrial chemicals and a significant reduction in animal tests Narrative This project is focused on the computational assessment of the safety of chemicals with the aim of reducing the burden of environmentally associated disease and dysfunctionand to promote the public s right to a healthyquality environment