In silico models for predicting ready biodegradability under REACH: A comparative study

摘要

REACH (Registration Evaluation Authorization and restriction of Chemicals) legislation is a new European law which aims to raise the human protection level and environmental health. Under REACH all chemicals manufactured or imported for more than one ton per year must be evaluated for their ready biodegradability. Ready biodegradability is also used as a screening test for persistent, bioaccumulative and toxic (PBT) substances. REACH encourages the use of non-testing methods such as QSAR (quantitative structure-activity relationship) models in order to save money and time and to reduce the number of animals used for scientific purposes. Some QSAR models are available for predicting ready biodegradability. We used a dataset of 722 compounds to test four models: VEGA, TOPKAT, BIOWIN 5 and 6 and START and compared their performance on the basis of the following parameters: accuracy, sensitivity, specificity and Matthew's correlation coefficient (MCC). Performance was analyzed from different points of view. The first calculation was done on the whole dataset and VEGA and TOPKAT gave the best accuracy (88% and 87% respectively). Then we considered the compounds inside and outside the training set: BIOWIN 6 and 5 gave the best results for accuracy (81%) outside training set. Another analysis examined the applicability domain (AD). VEGA had the highest value for compounds inside the AD for all the parameters taken into account. Finally, compounds outside the training set and in the AD of the models were considered to assess predictive ability. VEGA gave the best accuracy results (99%) for this group of chemicals. Generally, START model gave poor results. Since BIOWIN, TOPKAT and VEGA models performed well, they may be used to predict ready biodegradability.