MP6 Quantitative Structure Activity Relationships (QSARs)
Monday, 14 November 2005: 8:00 AM - 5:30 PM in Exhibit Hall

(HUG-1117-720112) Comparison of QSAR-based predictive software used for physical/chemical property estimation.

Hughes, D¹, MacPherson, H¹, Bose, R¹, ¹ Health Canada, New Substances Assessment and Control Bureau, Ottawa, Ontario, Canada

ABSTRACT- This preliminary study was aimed at comparing and evaluating QSAR software used for physical/chemical property predictions in the pre-market regulatory evaluation of new commercial chemical substances. In addition to test data, a variety of such estimates are utilized in the exposure and risk assessment of these substances. We wished to examine inter-estimate variability between the different software and additionally to compare the estimates with laboratory results. Estimated values for physical chemical endpoints generated by QSAR-based predictive software (ACD, EPISUITE, PALLAS, and SPARC which use a variety of QSAR methodologies) were utilized for new substances notified for assessment under the Canadian Environmental Protection Act. The sample consisted of several chemical categories of new substances (hindered amines, esters, acetamides, napthalenesulfonic acids, alcohols, amines, carboxylic acids, aldehydes, and urea derivatives) with varied uses (lubricants, catalysts, dyes, thickeners, corrosion inhibitors, coating additives, rheology additives, flame retardants, light stabilizers, carrier fluids etc.) for which ACD estimates were submitted by notifiers; we also generated estimates using other software, for comparison. The endpoints reported here include pKa (-5 to 18), log Kow (-4 to 27), and WS (10E-27 to 106 mg/L). The pKa estimates were found to demonstrate good correlation (SPARC vs ACD; R² = 0.93). The QSARs for log Kow were also found to yield reliable predictions (ACD vs SPARC; R² = 0.77; PALLAS vs KOWWIN; R² = 0.78, ACD vs KOWWIN; R² = 0.83, SPARC vs KOWWIN; R² = 0.88). The water solubility estimates were found to be the least consistent of the property estimates examined (SPARC vs WSKOW; R² = 0.65). The online software SPARC was not able to calculate properties for certain complex molecules and had usability problems. Any of these software examined would make comparable and acceptable predictions for most chemicals for the pKa and log Kow endpoints.

Key words: qsar, estimation