Parametrization of nanoparticles: development of full-particle nanodescriptors

nanoscale2016While metal oxide nanoparticles (NPs) are one of the most commonly used nanomaterials, the theoretical models used to analyze and predict their behavior have been mostly based on just the chemical composition or the extrapolation from small metal oxide clusters’ calculations. In this study, a set of novel, theoretical full-particle descriptors for modeling, grouping or read-across of metal oxide NP properties and biological activity was developed based on the force-field calculation of the potential energies of whole NPs. The capability of these nanodescriptors to group the nanomaterials acoording to their biological activity was demonstrated by Principal Component Analysis (PCA). The grouping provided by the PCA approach was found to be in good accordance with the algal growth inhibition data of well characterized nanoparticles, synthesized and measured inside the consortia of the EU 7FP framework MODERN project.

Tämm K, Sikk L, Burk J, Rallo R, Pokhrel S, Mädler L, Scott-Fordsmand JJ, Burk P, Tamm T. Parametrization of nanoparticles: development of full-particle nanodescriptors. Nanoscale 2016

  • DOI: 10.1039/c6nr04376c

Nano-QSAR: Genotoxicity of Multi-Walled Carbon Nanotubes

IJERThe study was carried out to develop an efficient approach for prediction the genotoxicity of carbon nanotubes. The experimental data on the bacterial reverse mutation test (TA100) on multi-walled carbon nanotubes (MWCNTs) was collected from the literature and examined as an endpoint. By means of the optimal descriptors calculated with the Monte Carlo method a mathematical model of the endpoint was built up. The model is represented by a function of: (i) dose (µg/plate); (ii) metabolic activation (i.e. with S9 mix or without S9 mix); and (iii) two types of MWCNTs. The above listed conditions were represented by so-called quasi-SMILES. Simplified molecular input-line entry system (SMILES) is a tool for representation of molecular structure. The quasi-SMILES is a tool to represent physicochemical and / or biochemical conditions for building up a predictive model. Thus, instead of well-known paradigm of predictive modeling “endpoint is a mathematical function of molecular structure” a fresh paradigm “endpoint is a mathematical function of available eclectic data (conditions) is suggested.

Toporova AP, Toporov AA, Rallo R, Leszczynska D, Leszczynski J. Nano-QSAR: Genotoxicity of Multi-Walled Carbon Nanotubes. Int. J. Environ. Res., 2016, 10(1): 59-64

  • DOI:

Trading in vivo for in silico: a new approach to nanotoxicity assessment

2015-11-20 11.29.43 amHistorically, market pressure has often resulted in scientific innovation being made available to consumers even before we were fully aware of its ins and outs. This was notably the case with asbestos, and the same scenario could very well be repeating with nanotechnology if proper safety assessment studies are not conducted and political measures taken. According to some of the latest forecasts, the nano- technology market will grow to reach US$ 75.8 (EUR 65.8) billion by 2020. And while engineered nanoparticles (eNPs) are already widespread in the likes of cosmetics, paint and electronics, we still don’t know much about their possible long- term effects on biological systems.

To gain a better understanding, scientists still rely heavily on animal testing — in spite of efforts from animal protection activists, scientists and policy makers to put the focus on alternative testing methods. In line with the EU’s efforts to implement appropriate testing strategies and with a view to overcoming the current obstacles to a wider adoption of in silico methods, Prof. Robert Rallo, coordinator of MODERN, initiated the MODERN project in January 2013.

A couple of months before the end of the project, he tells us about its achievements and expected impact on eNP toxicity assessment methods.

Research*eu Results Magazine

ISSN 1831-9947 (printed version)

ISSN 1977-4028 (PDF, EPUB)

In silico exploratory study using structure-activity relationship models and metabolic information for prediction of mutagenicity based on the Ames test and rodent micronucleus assay

sar-qsarThe mutagenic potential of chemicals is a cause of growing concern, due to the possible impact on human health. In this paper we have developed a knowledge-based approach, combining information from structure-activity relationship (SAR) and metabolic triggers generated from the metabolic fate of chemicals in biological systems for prediction of mutagenicity in vitro based on the Ames test and in vivo based on the rodent micronucleus assay. In the first part of the work, a model was developed, which comprises newly generated SAR rules and a set of metabolic triggers. These SAR rules and metabolic triggers were further externally validated to predict mutagenicity in vitro, with metabolic triggers being used only to predict mutagenicity of chemicals, which were predicted unknown, by SARpy. Hence, this model has a higher accuracy than the SAR model, with an accuracy of 89% for the training set and 75% for the external validation set. Subsequently, the results of the second part of this work enlist a set of metabolic triggers for prediction of mutagenicity in vivo, based on the rodent micronucleus assay. Finally, the results of the third part enlist a list of metabolic triggers to find similarities and differences in the mutagenic response of chemicals in vitro and in vivo.

Kamath P, Raitano G, Fernández A, Rallo R, Benfenati E.In silico exploratory study using structure-activity relationship models and metabolic information for prediction of mutagenicity based on the Ames test and rodent micronucleus assay. SAR and QSAR in Environmental Research, 2015, 11, xxxx-xxx

  • DOI: 10.1080/1062936X.2015.1108932

An ISA-TAB-Nano based data collection framework to support data-driven modelling of nanotoxicology

img_paper_nanoAnalysis of trends in nanotoxicology data and the development of data-driven models for nanotoxicity is facilitated by the reporting of data using a standardised electronic format. ISA-TAB-Nano has been proposed as such a format. However, in order to build useful datasets according to this format, a variety of issues has to be addressed. These issues include questions regarding exactly which (meta)data to report and how to report them. The current article discusses some of the challenges associated with the use of ISA-TAB-Nano and presents a set of resources designed to facilitate the manual creation of ISA-TAB-Nano datasets from the nanotoxicology literature. These resources were developed within the context of the NanoPUZZLES EU project and include data collection templates, corresponding business rules that extend the generic ISA-TAB-Nano specification as well as Python code to facilitate parsing and integration of these datasets within other nanoinformatics resources. The use of these resources is illustrated by a “Toy Dataset” presented in the Supporting Information. The strengths and weaknesses of the resources are discussed along with possible future developments.

Marchese-Robinson  RL, Cronin RTD, Richarz AN, Rallo R. An ISA-TAB-Nano based data collection framework to support data-driven modelling of nanotoxicology. Beilstein Journal of Nanotechnology, 2015, 6, 1978-1999

Prioritization of in silico models and molecular descriptors for the assessment of ready biodegradability

image_prioReady biodegradability is a key property for evaluating the long-term effects of chemicals on the environment and human health. As such, it is used as a screening test for the assessment of persistent, bioaccumulative and toxic substances. Regulators encourage the use of non-testing methods, such as in silico models, to save money and time. A dataset of 757 chemicals was collected to assess the performance of four freely availablein silico models that predict ready biodegradability. They were applied to develop a new consensus method that prioritizes the use of each individual model according to its performance on chemical subsets driven by the presence or absence of different molecular descriptors. This consensus method was capable of almost eliminating unpredictable chemicals, while the performance of combined models was substantially improved with respect to that of the individual models.

Fernández A, Rallo R, Giralt F. Prioritization of in silico models and molecular descriptors for the assessment of ready biodegradability. Environmental Research, 2015, 142, 161-168

Prediction of the Q-e parameters from structures of transfer chain agents

jprThe empirical parameters of copolymerization Q-e have been examined as an endpoint for establishing the quantitative structure – property relationships (QSPRs). The possibility to build up QSPR for these parameters is demonstrated for 22 transfer chain agents. Data for 20 taken in the literature and two were investigated in direct experiment. The statistical qualities of the models for parameter e together with the negative decimal logarithm of Q × 10−4 (pQ) are quite good. The mechanistic interpretation for these models are suggested and discussed.

Toropova AP, Toropov AA, Kudyshkin VO, Rallo R. Prediction of the Q-e parameters from structures of transfer chain agents. J. Polym. Res. 2015, 22:128

  • DOI: 10.1007/s10965-015-0778-3