Are some "safer alternatives" hazardous as PBTs? The case study of new flame retardants.

Some brominated flame retardants (BFRs), as PBDEs, are persistent, bioaccumulative, toxic (PBT) and are restricted/prohibited under various legislations. They are replaced by "safer" flame retardants (FRs), such as new BFRs or organophosphorous compounds. However, informations on the PBT behaviour of these substitutes are often lacking.

PBT assessment and prioritization by PBT Index and consensus modeling: comparison of screening results from structural models.

The limited availability of comprehensive data for Persistence, Bioaccumulation and Toxicity (PBT) of chemicals is a serious hindrance to the assignment of compounds to the categories of PBT and vPvB; REACH regulation requires authorization for the use of such chemicals, and additionally plans for safer alternatives. In the context of screening and priority-setting tools for PBT-assessment, the cumulative PBT Index model, implemented in QSARINS (QSAR-INSUBRIA), new software tool for the development and validation of multiple linear regression QSAR models, offers a new holistic approach for the identification of chemicals with cumulative PBT properties directly from their molecular structure. In this study the Insubria PBT Index in QSARINS is applied to the screening and prioritization of various data sets, containing a large variety of chemicals of heterogeneous molecular structure, previously screened by various authors by different methods, for their potential PBT behavior.

The QSPR-THESAURUS: the online platform of the CADASTER project.

The aim of the CADASTER project (CAse Studies on the Development and Application of in Silico Techniques for Environmental Hazard and Risk Assessment) was to exemplify REACH-related hazard assessments for four classes of chemical compound, namely, polybrominated diphenylethers, per and polyfluorinated compounds, (benzo)triazoles, and musks and fragrances. The QSPR-THESAURUS website (http: / /qspr-thesaurus.eu) was established as the project's online platform to upload, store, apply, and also create, models within the project.

QSARINS-chem: Insubria datasets and new QSAR/QSPR models for environmental pollutants in QSARINS.

A database of environmentally hazardous chemicals, collected and modeled by QSAR by the Insubria group, is included in the updated version of QSARINS, software recently proposed for the development and validation of QSAR models by the genetic algorithm-ordinary least squares method. In this version, a module, named QSARINS-Chem, includes several datasets of chemical structures and their corresponding endpoints (physicochemical properties and biological activities). The chemicals are accessible in different ways (CAS, SMILES, names and so forth) and their three-dimensional structure can be visualized.

Assessing predictive uncertainty in comparative toxicity potentials of triazoles.

Comparative toxicity potentials (CTPs) quantify the potential ecotoxicological impacts of chemicals per unit of emission. They are the product of a substance's environmental fate, exposure, and hazardous concentration. When empirical data are lacking, substance properties can be predicted.

Daphnia and fish toxicity of (benzo)triazoles: validated QSAR models, and interspecies quantitative activity-activity modelling.

Due to their chemical properties synthetic triazoles and benzo-triazoles ((B)TAZs) are mainly distributed to the water compartments in the environment, and because of their wide use the potential effects on aquatic organisms are cause of concern. Non testing approaches like those based on quantitative structure-activity relationships (QSARs) are valuable tools to maximize the information contained in existing experimental data and predict missing information while minimizing animal testing. In the present study, externally validated QSAR models for the prediction of acute (B)TAZs toxicity in Daphnia magna and Oncorhynchus mykiss have been developed according to the principles for the validation of QSARs and their acceptability for regulatory purposes, proposed by the Organization for Economic Co-operation and Development (OECD).

Evaluation of CADASTER QSAR models for the aquatic toxicity of (benzo)triazoles and prioritisation by consensus prediction.

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.

QSAR Modeling is not "Push a Button and Find a Correlation": A Case Study of Toxicity of (Benzo-)triazoles on Algae.

A case study of toxicity of (benzo)triazoles ((B)TAZs) to the algae Pseudokirchneriella subcapitata is used to discuss some problems and solutions in QSAR modeling, particularly in the environmental context. The relevance of data curation (not only of experimental data, but also of chemical structures and input formats for the calculation of molecular descriptors), the crucial points of QSAR model validation and the potential application for new chemicals (internal robustness, exclusion of chance correlation, external predictivity, applicability domain) are described, while developing MLR-OLS models based on molecular descriptors, calculated by various QSAR software tools (commercial DRAGON, free PaDEL-Descriptor and QSPR-THESAURUS). Additionally, the utility of consensus models is highlighted.