ATLA 42.1, March 2014

//ATLA 42.1, March 2014

ATLA 42 Issue 1 March 2014

The Importance of Multidisciplinary Skills in Research and Development

David J. Livingstone

The Marie Curie Training Network, Environmental ChemO informatics (ECO), has been of great importance. Not only has it created a platform for the production of valuable contributions in a number of fields through the various research projects,  but, more importantly, it has also provided training in a range of complementary techniques for the researchers of the future.
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News & Views

ATLA Staff Writer

Spinal Cord Injury Model
Bleeding Might Affect Horseshoe Crab Behaviour
Pathway-based Human Phenotype Network
In Vitro Cardiac Tissue Model
Mechanical Behaviour Testing of Tissue Engineering Scaffolds
In Vitro Model of Bone Metastasis
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Experimental and Theoretical Studies in the EU FP7 Marie Curie Initial Training Network Project, Environmental ChemOinformatics (ECO)

Igor V. Tetko, Karl-Werner Schramm, Thomas Knepper, Willie J.G.M. Peijnenburg, A. Jan Hendriks, Jose M. Navas, Ian A. Nicholls, Tomas Öberg, Roberto Todeschini, Eva Schlosser and Stefan Brandmaier

The Need for In Silico Methods in REACH
The Environmental ChemOinformatics Project
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The QSPR-THESAURUS: The Online Platform of the CADASTER Project

Stefan Brandmaier, Willie Peijnenburg, Mojca K. Durjava, Boris Kolar, Paola Gramatica, Ester Papa, Barun Bhhatarai, Simona Kovarich, Stefano Cassani, Partha Pratim Roy, Magnus Rahmberg, Tomas Öberg, Nina Jeliazkova, Laura Golsteijn, Mike Comber, Larisa Charochkina, Sergii Novotarskyi, Iurii Sushko, Ahmed Abdelaziz, Elisa D’Onofrio, Prakash Kunwar, Fiorella Ruggiu and Igor V. Tetko

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 ( 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.
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Chlorotriazines Do Not Activate the Aryl Hydrocarbon Receptor, the Oestrogen Receptor or the Thyroid Receptor in In Vitro

Irene de la Casa-Resino, José M. Navas and María L. Fernández-Cruz

Prediction of Acute Aquatic Toxicity Toward Daphnia magna by using the GA-kNN Method

Matteo Cassotti, Davide Ballabio, Viviana Consonni, Andrea Mauri, Igor V. Tetko, and Roberto Todeschini

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 (R2 and Q2 cv equal to 0.78, Q2ext 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.

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The Application of QSAR Approaches to Nanoparticles

Jacques Ehret, Martina Vijver and Willie Peijnenburg

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.
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2017-01-09T06:38:42+00:00 Tags: , |

Estimation of the Toxicity of Silver Nanoparticles by Using Planarian Flatworms

Leonid Kustov, Kharlampii Tiras, Souhail Al-Abed, Natalia Golovina and Mikhail

The regeneration of planarian flatworms — specifically, changes to the area of the regeneration bud (blastema) after surgical dissection — was proposed for use as a robust tool for estimating the toxicity of silver nanoparticles. The use of Planaria species, due to their unique regenerative capacity, could  result in a reduction in the use of more-traditional laboratory animals for toxicity testing. With our novel approach, silver nanoparticles were found to be moderately toxic to the planarian, Girardia tigrina.
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Mechanistically-based QSARs to Describe Metabolic Constants in Mammals

Alessandra Pirovano, Mark A.J. Huijbregts, Ad M.J. Ragas, Karin Veltman1 and A. Jan Hendriks

Biotransformation is one of the processes which influence the bioaccumulation of chemicals. The enzymatic action of metabolism involves two processes, i.e. the binding of the substrate to the enzyme followed by a catalytic reaction, which are described by the Michaelis–Menten constant (Km) and the maximum rate (Vmax). Here, we developed Quantitative Structure–Activity Relationships (QSARs) for Log(1/Km) and LogVmax for substrates of four enzyme classes. We focused on oxidations catalysed by alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), flavin-containing monooxygenase (FMO) and cytochrome P450 (CYP) in mammals. The chemicals investigated were xenobiotics, including alcohols, aldehydes, pesticides and drugs. We applied general linear models for this purpose, employing descriptors related to partitioning, geometric characteristics, and electronic properties of the substrates, which can be interpreted mechanistically. The explained variance of the QSARs varied between 20% and 70%, and it was larger for Log(1/Km) than for LogVmax. The increase of 1/Km with compound logP and size suggests that weak interactions are important, e.g. by substrate binding via desolvation processes. The importance of electronic factors for 1/Km was described in relation to the catalytic mechanism of the enzymes. Vmax was particularly influenced by electronic properties, such as dipole moment and energy of the lowest unoccupied molecular orbital. This can be explained by the nature of the catalysis, characterised by the cleavage and formation of covalent or ionic bonds (strong interactions). The present study may be helpful to understand the underlying principles of the chemical specific activity of four important oxidising enzymes.
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2017-01-09T06:38:42+00:00 Tags: , , , |

Ethoxyresorufin-O-deethylase (EROD) Activity Modulationof 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

Rajesh Rathore and Karl-Werner Schramm

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.
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