Prediction of the biodegradation of chemicals using OECD QSAR Toolbox software

Abstract

Introduction. The development of integrated approaches to testing, assessment of the hazard and exposure risk of chemicals on human health and the environment is one of the priorities of preventive toxicology. An integrated approach involves various combinations of methods in silico, in chemico, in vitro, ex vivo, in vivo for hazard assessment. In the Russian Federation, in silico methods are often perceived with skepticism, mainly due to the lack of their legal status, weak methodological base and insufficient training of specialists. In order to expand the methodological base, the possibility of predicting the stability of chemicals in biotic conditions using the OECD QSAR Toolbox software was studied. Material and methods. The OECD QSAR Toolbox software version 4.4.1., OECD guidelines on the assessment of biodegradation of chemicals. Results. The world community and the OECD have developed and implemented a three-level system for chemicals biodegradation testing, which includes tests for readily biodegradation (OECD Guidelines 301 A, 301 B, 301 C, 301 D, 301 E, 301 F, 306, 310), tests to determine the potential biodegradability (OECD Guidelines 302 A, 302 B, 302 C, 304 A) and model systems tests (OECD Guidelines 303 A, 303 B). To test the capabilities of the program, 24 endpoints were selected. They are the determination of biodegradability (%) by BOD, DOC, CO2, CH4 releases in OECD tests 301 A, 301 B, 301 C, 301 D, 302 C, 302 B, biodegradability (%) in sediments and soil, bioconcentration factors for more than 100 organic chemicals of various structures. The parameters were calculated using the analog method, followed by mandatory interpretation of the data obtained by an expert. When predicting the biodegradability of chemicals, it is necessary to perform a series of calculations using different tests (OECD tests 301 A, 301 B, 301 C, 301 D, 301 E, 302 B are preferred) and grouping methods followed by a comprehensive assessment of the results obtained, taking into account not only the structural similarity of substances and analogues, but also the quality of the experimental data used. When predicting biodegradability by BOD values, it is advisable to use the OECD 301 C test. The proportion of tested substances whose biodegradability could be estimated by BOD values is about 50% in the OECD 301 C test, which is primarily due to the presence of a significant amount of experimental data. The calculation of bioconcentration factors seems to be promising. For about 45% of the tested substances, it was possible to calculate bioconcentration coefficients with good correlation with experimental data. Biodegradation in soil (% and half-life) can be predicted only for a very limited range of compounds (10% of the tested substances), which is due to the difficulty of selecting structurally similar analogues with experimental data. The method is not applicable for predicting the biodegradation of salts, organometallic compounds, polymer molecules and mixed products. Conclusion. The Russian Register of Potentially Hazardous Chemical and Biological Substances has developed a methodological guide for predicting the stability of chemicals in biotic conditions using the OECD QSAR Toolbox software. The document presents algorithms for calculating biodegradability (%) according to OECD tests 301, 302, 303; BOD, bioconcentration factors and biodegradability (%) in soil.