| 1. |
- Cassani, Stefano, et al.
(författare)
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Evaluation of CADASTER QSAR Models for the Aquatic Toxicity of (Benzo)triazoles and Prioritisation by Consensus Prediction
- 2013
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Ingår i: ATLA (Alternatives to Laboratory Animals). - : SAGE Publications. - 0261-1929. ; 41:1, s. 49-64
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Tidskriftsartikel (refereegranskat)abstract
- QSAR regression models of the toxicity of triazoles and benzotriazoles ([B] TAZs) to an alga (Pseudokirchneriella subcapitata), Daphnia magna and a fish (Onchorhynchus mykiss), were developed by five partners in the FP7-EU Project, CADASTER. The models were developed by different methods - Ordinary Least Squares (OLS), Partial Least Squares (PLS), Bayesian regularised regression and Associative Neural Network (ASNN) - by using various molecular descriptors (DRAGON, PaDEL-Descriptor and QSPR-THESAURUS web). In addition, different procedures were used for variable selection, validation and applicability domain inspection. The predictions of the models developed, as well as those obtained in a consensus approach by averaging the data predicted from each model, were compared with the results of experimental tests that were performed by two CADASTER partners. The individual and consensus models were able to correctly predict the toxicity classes of the chemicals tested in the CADASTER project, confirming the utility of the QSAR approach. The models were also used for the prediction of aquatic toxicity of over 300 (B)TAZs, many of which are included in the REACH pre-registration list, and were without experimental data. This highlights the importance of QSAR models for the screening and prioritisation of untested chemicals, in order to reduce and focus experimental testing.
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| 2. |
- Durjava, Mojca Kos, et al.
(författare)
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Experimental Assessment of the Environmental Fate and Effects of Triazoles and Benzotriazole
- 2013
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Ingår i: ATLA (Alternatives to Laboratory Animals). - : SAGE Publications. - 0261-1929. ; 41:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- The environmental fate and effects of triazoles and benzotriazoles are of concern within the context of chemical regulation. As part of an intelligent testing strategy, experimental tests were performed on endpoints that are relevant for risk assessment. The experimental tests included the assessment of eco-toxicity to an alga, a daphnid and zebrafish embryos, and the assessment of ready biodegradability. Triazole and benzotriazole compounds were selected for testing, based on existing toxicity data for vertebrate and invertebrate species, as well as on the principal component analysis of molecular descriptors aimed at selecting the minimum number of test compounds in order to maximise the chemical domain spanned for both compound classes. The experimental results show that variation in the toxicities of triazoles and benzotriazole across species was relatively minor; in general, the largest factor was approximately 20. The study conducted indicated that triazoles are not readily biodegradable.
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| 3. |
- Iqbal, Muhammad Sarfraz, et al.
(författare)
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Understanding quantitative structure-property relationships uncertainty in environmental fate modeling
- 2013
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 32:5, s. 1069-1076
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Tidskriftsartikel (refereegranskat)abstract
- In cases in which experimental data on chemical-specific input parameters are lacking, chemical regulations allow the use of alternatives to testing, such as in silico predictions based on quantitative structure–property relationships (QSPRs). Such predictions are often given as point estimates; however, little is known about the extent to which uncertainties associated with QSPR predictions contribute to uncertainty in fate assessments. In the present study, QSPR-induced uncertainty in overall persistence (POV) and long-range transport potential (LRTP) was studied by integrating QSPRs into probabilistic assessments of five polybrominated diphenyl ethers (PBDEs), using the multimedia fate model Simplebox. The uncertainty analysis considered QSPR predictions of the fate input parameters' melting point, water solubility, vapor pressure, organic carbon–water partition coefficient, hydroxyl radical degradation, biodegradation, and photolytic degradation. Uncertainty in POV and LRTP was dominated by the uncertainty in direct photolysis and the biodegradation half-life in water. However, the QSPRs developed specifically for PBDEs had a relatively low contribution to uncertainty. These findings suggest that the reliability of the ranking of PBDEs on the basis of POV and LRTP can be substantially improved by developing better QSPRs to estimate degradation properties. The present study demonstrates the use of uncertainty and sensitivity analyses in nontesting strategies and highlights the need for guidance when compounds fall outside the applicability domain of a QSPR.
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