Prediction of biodegradability from chemical structure: Modeling of ready biodegradation test data

Biodegradation data were collected and evaluated for 894 substances with wi dely varying chemical structures. All data were determined according to the Japanese Ministry of International Trade and Industry (MITI) I test protoc ol. The MITI I test is a screening test for ready biodegradability and has been described by Organization for Economic Cooperation and Development (OE CD) test guideline 301 C and European Union (EU) test guideline C4E The che micals were characterized by a set of 127 predefined structural fragments. This data set was used to develop a model for the prediction of the biodegr adability of chemicals under standardized OECD and EU ready biodegradation test conditions. Partial least squares (PLS) discriminant analysis was used for the model development. The model was evaluated by means of internal cr oss-validation and repeated external validation. The importance of various structural fragments and fragment interactions was investigated. The most i mportant fragments include the presence of a long alkyl chain; hydroxy, est er, and acid groups (enhancing biodegradation); and the presence of one or more aromatic rings and halogen substituents (retarding biodegradation). Mo re than 85% of the model predictions were correct for using the complete da ta set. The not readily biodegradable predictions were slightly better than the readily biodegradable predictions (86 vs 84%). The average percentage of correct predictions from four external validation studies was 83%. Model optimization by including fragment interactions improved the model predict ing capabilities to 89%. It can be concluded that the PLS model provides pr edictions of high reliability for a diverse range of chemical structures. T he predictions conform to the concept of readily biodegradable (or not read ily biodegradable) as defined by OECD and EU test guidelines.