TY  - JOUR
AB  - 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. We overview the main features of the website, such as model upload, experimental design and hazard assessment to support risk assessment, and integration with other web tools, all of which are essential parts of the QSPR-THESAURUS.
AU  - Brandmaier, S.
AU  - Peijnenburg, W.*
AU  - Durjava, M.K.*
AU  - Kolar, B.*
AU  - Gramatica, P.*
AU  - Papa, E.*
AU  - Bhhatarai, B.*
AU  - Kovarich, S.*
AU  - Cassani, S.*
AU  - Roy, P.P.*
AU  - Rahmberg, M.*
AU  - Öberg, T.*
AU  - Jeliazkova, N.*
AU  - Golsteijn, L.*
AU  - Comber, M.*
AU  - Charochkina, L.*
AU  - Novotarskyi, S.*
AU  - Sushko, I.*
AU  - Abdelaziz, A.*
AU  - D'Onofrio, E.
AU  - Kunwar, P.
AU  - Ruggiu, F.
AU  - Tetko, I.V.
C1  - 31177
C2  - 34185
SP  - 13-24
TI  - The QSPR-THESAURUS: The online platform of the CADASTER project.
JO  - ATLA-Altern. Lab. Anim.
VL  - 42
IS  - 1
PY  - 2014
SN  - 0261-1929
ER  - 

TY  - JOUR
AB  - In this study, a QSAR model was developed from a data set consisting of 546 organic molecules, to predict acute aquatic toxicity toward Daphnia magna. A modified k-Nearest Neighbour (kNN) strategy was used as the regression method, which provided prediction only for those molecules with an average distance from the k nearest neighbours lower than a selected threshold. The final model showed good performance (R(2) and Q(2) cv equal to 0.78, Q(2) ext equal to 0.72). It comprised eight molecular descriptors that encoded information about lipophilicity, the formation of H-bonds, polar surface area, polarisability, nucleophilicity and electrophilicity.
AU  - Cassotti, M.*
AU  - Ballabio, D.*
AU  - Consonni, V.*
AU  - Mauri, A.*
AU  - Tetko, I.V.
AU  - Todeschini, R.*
C1  - 31524
C2  - 34506
SP  - 31-41
TI  - Prediction of acute aquatic toxicity toward Daphnia magna by using the GA-kNN method.
JO  - ATLA-Altern. Lab. Anim.
VL  - 42
IS  - 1
PY  - 2014
SN  - 0261-1929
ER  - 

TY  - JOUR
AB  - Nanoparticles (NPs) are increasingly used throughout the world for many purposes. The resulting exposure increases the relevance of efforts to assess their effects. The activities of NPs are related to many structural features, including their shape, composition and size. Applying Quantitative Structure-Activity Relationship (QSAR) methods to nanoscale systems becomes challenging, due to the lack of data and insight into the fate and effects of NPs. In this study, the possible use of QSAR methods on NPs is investigated. To this intent, several ways of representing and describing NPs were tested by using different data mining methods. The main conclusion is that QSAR methods are relevant for the study of the activity of NPs, but this should be confirmed by using larger and more diverse sets of data. Moreover, representing the constitution of NPs (in terms of core, coating and surface modification) significantly increases the prediction accuracy of the models. In our case, the most significant features to be represented were found to be the core and surface modification.
AU  - Ehret, J.
AU  - Vijver, M.*
AU  - Peijnenburg, W.*
C1  - 31176
C2  - 34215
SP  - 43-50
TI  - The application of QSAR approaches to nanoparticles.
JO  - ATLA-Altern. Lab. Anim.
VL  - 42
IS  - 1
PY  - 2014
SN  - 0261-1929
ER  - 

TY  - JOUR
AB  - The increase in commercial production and inevitable release of fullerenes into the environment accelerates concerns about their potential toxicity. Furthermore, the concomitant release of xenobiotics poses a health hazard to humans, and might present potential long-term risks to human health. In the present study, we found that an aqueous suspension of buckminsterfullerene (aqu-nC60) does not result in the induction of ethoxyresorufin-O-deethylase (EROD) activity in H4IIE rat liver cells in vitro. The simultaneous and sequential exposure of aqu-nC60 and the dioxin TCDD induces EROD activity to the same extent as TCDD alone (i.e. in the absence of fullerene), in spite of the high affinity of C60 for TCDD. However, the co-exposure of aqu-nC60 and PCB 126 induces elevated EROD activity, and sequential exposure increases responses 2-fold compared to the control samples. Our in vitro observations suggest a potential source of drug-drug type interaction of fullerene with xenobiotics, particularly after a sequential exposure.
AU  - Rathore, R.
AU  - Schramm, K.-W.
C1  - 31175
C2  - 34216
SP  - 71-80
TI  - Ethoxyresorufin-O-Deethylase (EROD) activity modulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) in the presence of aqueous suspensions of nano-C60.
JO  - ATLA-Altern. Lab. Anim.
VL  - 42
IS  - 1
PY  - 2014
SN  - 0261-1929
ER  - 

TY  - JOUR
AU  - Tetko, I.V.
AU  - Schramm, K.-W.
AU  - Knepper, T.*
AU  - Peijnenburg, W.J.*
AU  - Hendriks, A.J.*
AU  - Navas, J.M.*
AU  - Nicholls, I.A.*
AU  - Öberg, T.*
AU  - Todeschini, R.*
AU  - Schlosser, E.
AU  - Brandmaier, S.
C1  - 31178
C2  - 34194
SP  - 7-11
TI  - Experimental and theoretical studies in the EU FP7 Marie Curie Initial Training Network Project, Environmental ChemOinformatics (ECO).
JO  - ATLA-Altern. Lab. Anim.
VL  - 42
IS  - 1
PY  - 2014
SN  - 0261-1929
ER  - 

TY  - JOUR
AB  - The importance of reliable methods for representative sub-sampling in terms of experimental design and risk assessment within the European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) system is crucial. We developed experimental design approaches, by utilising predicted properties and the 'distance to model' parameter, to estimate the benefits of certain compounds to the quality of a resulting model. A statistical evaluation of four regression data sets and one classification data set showed that the adaptive concept of iteratively refining the representation of the chemical space contributes to a more efficient and more reliable selection in comparison to traditional approaches. The evaluation of compounds with regard to the uncertainty and the correlation of prediction is beneficial, and in particular, for regression data sets of sufficient size, whereas the use of predicted properties to define the chemical space is beneficial for classification models.
AU  - Brandmaier, S.
AU  - Novotarskyi, S.*
AU  - Sushko, I.*
AU  - Tetko, I.V.
C1  - 26086
C2  - 32062
SP  - 33-47
TI  - From descriptors to predicted properties: Experimental design by using applicability domain estimation.
JO  - ATLA-Altern. Lab. Anim.
VL  - 41
IS  - 1
PB  - Frame
PY  - 2013
SN  - 0261-1929
ER  - 

TY  - JOUR
AB  - 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.
AU  - Cassani, S.*
AU  - Kovarich, S.*
AU  - Papa, E.*
AU  - Roy, P.P.*
AU  - Rahmberg, M.*
AU  - Nilsson, S.*
AU  - Sahlin, U.*
AU  - Jeliazkova, N.*
AU  - Kochev, N.*
AU  - Pukalov, O.*
AU  - Tetko, I.V.
AU  - Brandmaier, S.
AU  - Durjava, M.K.*
AU  - Kolar, B.*
AU  - Peijnenburg, W.*
AU  - Gramatica, P.*
C1  - 26100
C2  - 32069
SP  - 49-64
TI  - Evaluation of CADASTER QSAR models for the aquatic toxicity of (benzo)triazoles and prioritisation by consensus prediction.
JO  - ATLA-Altern. Lab. Anim.
VL  - 41
IS  - 1
PB  - Frame
PY  - 2013
SN  - 0261-1929
ER  - 

TY  - JOUR
AU  - Peijnenburg, W.J.*
AU  - Tetko, I.V.
C1  - 26212
C2  - 32125
SP  - 13-17
TI  - Exemplification of the implementation of alternatives to experimental testing in chemical risk assessment - case studies from the CADASTER Project. Preface.
JO  - ATLA-Altern. Lab. Anim.
VL  - 41
IS  - 1
PB  - Frame
PY  - 2013
SN  - 0261-1929
ER  - 

TY  - JOUR
AB  - The prioritisation of chemical compounds is important for the identification of those chemicals that represent the highest threat to the environment. As part of the CADASTER project (http: / /www.cadaster.eu), we developed an online web tool that allows the calculation of the environmental risk of chemical compounds from a web interface. The environmental fate of compounds in the aquatic compartment is assessed by using the SimpleBox model, while adverse effects on the aquatic compartment are assessed by the Species Sensitivity Distribution approach. The main purpose of this web tool is to exemplify the use of quantitative structure-activity relationships (QSARs) to support risk assessment. A case study of QSAR integrated risk assessment of 209 polybrominated diphenyl ethers (PBDEs) demonstrates the treatment and influence of uncertainty in the predicted physicochemical and toxicity parameters in probabilistic risk assessment.
AU  - Tetko, I.V.
AU  - Sopasakis, P.
AU  - Kunwar, P.
AU  - Brandmaier, S.
AU  - Novoratskyi, S.*
AU  - Charochkina, L.*
AU  - Prokopenko, V.*
AU  - Peijnenburg, W.J.*
C1  - 26252
C2  - 32145
SP  - 127-135
TI  - Prioritisation of Polybrominated Diphenyl Ethers (PBDEs) by using the QSPR-THESAURUS web tool.
JO  - ATLA-Altern. Lab. Anim.
VL  - 41
IS  - 1
PB  - Frame
PY  - 2013
SN  - 0261-1929
ER  -