A combined QSAR and partial order ranking approach to risk assessment

Abstract

QSAR generated data appear as an attractive alternative to experimental data as foreseen in the proposed new chemicals legislation REACH. A preliminary risk assessment for the aquatic environment can be based on few factors, i.e. the octanol-water partition coefficient (K_ow ), the vapour pressure (VP) and the potential biodegradability of the compound in combination with the predicted no-effect concentration (PNEC) and the actual tonnage in which the substance is produced. Application of partial order ranking, allowing simultaneous inclusion of several parameters leads to a mutual prioritisation of the investigated substances, the prioritisation possibly being further analysed through the concept of linear extensions and average ranks. The ranking uses endpoint values (log K_ow and log VP) derived from strictly linear ‘noise-deficient’ QSAR models as input parameters. Biodegradation estimates were adopted from the BioWin module of the EPI Suite. The population growth impairment of Tetrahymena pyriformis was used as a surrogate for fish lethality.

†Presented at CMTPI 2005: Computational Methods in Toxicology and Pharmacology Integrating Internet resources (Shanghai, China, October 29–November 1 2005).

Keywords:

• QSAR
• EPI Win
• Partial order ranking
• Hasse diagrams
• Risk assessment
• Anilines

Notes

†Presented at CMTPI 2005: Computational Methods in Toxicology and Pharmacology Integrating Internet resources (Shanghai, China, October 29–November 1 2005).