Evaluation of the availability and applicability of computational approaches in the safety assessment of nanomaterials: Final report of the Nanocomput project

This is the final report of the Nanocomput project, the main aims of which were to review the current status of computational methods that are potentially useful for predicting the properties of engineered nanomaterials, and to assess their applicability in order to provide advice on the use of these approaches for the purposes of the REACH regulation. Since computational methods cover a broad range of models and tools, emphasis was placed on Quantitative Structure-Property Relationship (QSPR) and Quantitative Structure-Activity Relationship (QSAR) models, and their potential role in predicting NM properties. In addition, the status of a diverse array of compartment-based mathematical models was assessed. These models comprised toxicokinetic (TK), toxicodynamic (TD), in vitro and in vivo dosimetry, and environmental fate models. Finally, based on systematic reviews of the scientific literature, as well as the outputs of the EU-funded research projects, recommendations for further research and development were also made. The Nanocomput project was carried out by the European Commission’s Joint Research Centre (JRC) for the Directorate-General (DG) for Internal Market, Industry, Entrepreneurship and SMEs (DG GROW) under the terms of an Administrative Arrangement between JRC and DG GROW. The project lasted 39 months, from January 2014 to March 2017, and was supported by a steering group with representatives from DG GROW, DG Environment and the European Chemicals Agency (ECHA).JRC.F.3-Chemicals Safety and Alternative Method

Molecular Similarity and Xenobiotic Metabolism

MetaPrint2D, a new software tool implementing a data-mining approach for predicting sites of xenobiotic metabolism has been developed. The algorithm is based on a statistical analysis of the occurrences of atom centred circular fingerprints in both substrates and metabolites. This approach has undergone extensive evaluation and been shown to be of comparable accuracy to current best-in-class tools, but is able to make much faster predictions, for the first time enabling chemists to explore the effects of structural modifications on a compound’s metabolism in a highly responsive and interactive manner.MetaPrint2D is able to assign a confidence score to the predictions it generates, based on the availability of relevant data and the degree to which a compound is modelled by the algorithm.In the course of the evaluation of MetaPrint2D a novel metric for assessing the performance of site of metabolism predictions has been introduced. This overcomes the bias introduced by molecule size and the number of sites of metabolism inherent to the most commonly reported metrics used to evaluate site of metabolism predictions.This data mining approach to site of metabolism prediction has been augmented by a set of reaction type definitions to produce MetaPrint2D-React, enabling prediction of the types of transformations a compound is likely to undergo and the metabolites that are formed. This approach has been evaluated against both historical data and metabolic schemes reported in a number of recently published studies. Results suggest that the ability of this method to predict metabolic transformations is highly dependent on the relevance of the training set data to the query compounds.MetaPrint2D has been released as an open source software library, and both MetaPrint2D and MetaPrint2D-React are available for chemists to use through the Unilever Centre for Molecular Science Informatics website.----Boehringer-Ingelhie

Synthesis of zwitterionic compounds for aquatic toxicity testing for QSAR correlation studies.

22 zwitterionic compounds (10 short-chain surfactants; 12 non-surfactants) were synthesised obeying the general formula R-N+(CH3)2(CH2)nSO3', where n = 2 to 4, by reacting the corresponding N, N-dimethylamines with either sodium-2-chloroethane sulfonate (n = 2), 1, 3- propanesulfonate (n = 3) or 1,4-butanesulfonate (n = 4). The R group varied from a C6 to C12 alkyl chain, to a phenylalkyl unit bearing a Cl to C4 chain and finally to a phenylpropyl unit with a C4 to C6 para-substituted alkyl group. Octanol/water partition coefficients of the 22 sulfobetaines were determined by a conventional stir-flask procedure. The amount of solute in both the octanol and water layer was quantified using a reverse-phase HPLC technique. A UV detection mechanism was employed for those sulfobetaines that possessed a suitable chromophore for UV detection and an electrospray ionisation mode of detection was used for the analysis of those sulfobetaines that lacked a chromophore suitable for UV detection. Acute aquatic toxicity to the aquatic invertebrate, Daphnia magna Straus, was reported as log (l/EC50). The EC50 values were determined experimentally using a standard Acute Immobilisation Test recommended by the OECD Guideline 202 and the internal Unilever document, Ecotoxicology SOP 019 11. A log P-based QS AR was then derived which was found to be analogous to the standard polar narcosis equation, suggesting that zwitterionic sulfobetaines act as polar narcotics. Experimental log P determined by the stir-flask procedure and the rules of Rekker and Roberts for the calculation of log P for quaternary ammonium compounds of the cationic type, were then used in the derivation of key fragment values and interaction factors for use in log P calculations of sulfobetaines using the Leo and Hansch approach. Furthermore, log P predictions provided by KowWin, a computerised program developed by the Syracause Research Cooperation, were suitably amended to take into consideration our experimental results. Finally, an investigation into the suitability of the phospholipophilicity parameter, log k'lAM, for defining aquatic toxicity was performed and the efficacy of using this parameter and log P to predict aquatic toxicity was compared. In addition, other chromatographic methods for estimating log P were investigated. These include the indirect reverse-phase HPLC method, the direct reverse-phase HPLC method and Counter Current Chromatography

Skin Tissue Models

Skin Tissue Models provides a translational link for biomedical researchers on the interdisciplinary approaches to skin regeneration. As the skin is the largest organ in the body, engineered substitutes have critical medical application to patients with disease and injury - from burn wounds and surgical scars, to vitiligo, psoriasis and even plastic surgery. This volume offers readers preliminary description of the normal structure and function of mammalian skin, exposure to clinical problems and disease, coverage of potential therapeutic molecules and testing, skin substitutes, models as study platforms of skin biology and emerging technologies. The editors have created a table of contents which frames the relevance of skin tissue models for researchers as platforms to study skin biology and therapeutic approaches for different skin diseases, for clinicians as tissue substitutes, and for cosmetic and pharmaceutical industries as alternative test substrates that can replace animal models. Offers descriptions of the normal structure/function of mammalian skin, exposure to clinical problems, and more Presents coverage of skin diseases (cancer, genodermatoses, vitiligo and psoriasis) that extends to clinical requirements and skin diseases in vitro models Addresses legal requirements and ethical concerns in drugs and cosmetics in vitro testing Edited and authored by internationally renowned group of researchers, presenting the broadest coverage possible. © 2018 Elsevier Inc. All rights reserved.(undefined)info:eu-repo/semantics/publishedVersio

Landscape processes and management practices affecting phosphorous loss

Master of ScienceDepartment of AgronomyNathan O NelsonPhosphorous (P) loss from non-point agricultural sources is an important factor that affects the deterioration of surface water quality. Excessive P inputs can exacerbate eutrophication and toxic algal blooms, thus leading to greater water treatment costs and reduced recreational value of water bodies. To reduce non-point source P loss, we need to go back to the source and help farmers and ranchers make better land management decisions. One tool that can help is the P index. The P Index rating can provide information on major P loss pathways and help producers adjust land management decisions to minimize P loss from a specific field. Currently, the Kansas P index does not meet USDA-NRCS standards as listed in Title 190, which was updated in 2017. Among other items, updating the P index will require estimates of long-term annual runoff for soils and cropping systems across Kansas. Additional research is needed to identify a method of estimating runoff volume and to update the P index to current standards. Soil erosion presents one of the greatest concerns to most P mitigation programs worldwide because the majority of P loss occurs with eroded sediments. Ephemeral gully erosion is a type of erosion that can remove large quantities of sediment and is particularly difficult to control in no-till agriculture. Ephemeral gullies can develop in areas of concentrated flow within cultivated crop fields. Additional research is needed to identify best management practices that can reduce ephemeral gully erosion in no-till systems. The objectives of this research are to i) develop and evaluate a new approach to estimate long-term average annual runoff from agricultural fields, ii) develop a revised P index, and iii) investigate the effect of cover crops on ephemeral gully erosion. Two methods were evaluated to estimate long-term average annual runoff: use of the standard curve number (CN) approach with a daily time-step on long-term historical datasets (method 1) or a modified CN approach that uses long-term average annual rainfall and assumes an exponential distribution of rainfall (method 2). Both methods were calibrated and evaluated with edge-of-field monitoring data. The calibrated method 2 results revealed an R2 = 0.88, NSE = 0.56 and when validating this method R2 = 0.66, NSE = 0.54 indicating that this model had good model performance and that no further calibration was needed. The proposed P index is structured as a component P-index. Inputs were updated to include estimated average annual runoff calculated with the previously described modified CN approach. The coefficients for the P index components were developed through multiple linear regression with SAS proc mixed using a database of P loss estimates for 1360 cropping scenarios. Validation of the revised P index was conducted by relating the P index values to measured P loss data using both annual and summarized data from edge-of-field runoff experiments located in Riley, Crawford, Franklin, and Geary County. Coefficients to the revised P index were all significant at p<0.0001. Results showed that the proposed P index improved the relationship between the P index and P loss from R2= 0.41 to R2= 0.82 and validation of revised P index to the current index improved relationship between the P index and P loss from R2= 0.09 to R2= 0.71 using annual data and from R2= 0.73 to R2= 0.85 using average annual P loss data. The revised P index had improved model performance and would be a sufficient model to use for the Kansas P index. The final portion of this research was conducted in the summers of 2021 and 2022 at the Kansas Agricultural Watershed (KAW) field laboratory located near Manhattan, KS, USA. Ephemeral gully length, depth and width were measured and used to determine the volume of sediment lost through ephemeral gully erosion. Elevation data from an unmanned aerial vehicle (UAV) was collected in fall of 2016, 2020, and 2022 to determine ephemeral gully formations using ArcGIS Pro to compare elevation data. Results did not identify a significant effect of cover crops on ephemeral gully erosion. This could be due to insufficient ephemeral gully erosion in the watersheds at the KAW field lab. Furthermore, Elevation data collected by aerial imagery did not prove useful in quantifying the soil loss from ephemeral gullies. Results from this research will help producers and land managers more accurately evaluate effects of agricultural management systems on the risk of P loss to surface water using a revised P-index. The revised P index will also help producers identify the mechanisms responsible for P loss from their fields and thereby select conservation practice systems that can most effectively reduce those P losses

High-Performance Modelling and Simulation for Big Data Applications

This open access book was prepared as a Final Publication of the COST Action IC1406 “High-Performance Modelling and Simulation for Big Data Applications (cHiPSet)“ project. Long considered important pillars of the scientific method, Modelling and Simulation have evolved from traditional discrete numerical methods to complex data-intensive continuous analytical optimisations. Resolution, scale, and accuracy have become essential to predict and analyse natural and complex systems in science and engineering. When their level of abstraction raises to have a better discernment of the domain at hand, their representation gets increasingly demanding for computational and data resources. On the other hand, High Performance Computing typically entails the effective use of parallel and distributed processing units coupled with efficient storage, communication and visualisation systems to underpin complex data-intensive applications in distinct scientific and technical domains. It is then arguably required to have a seamless interaction of High Performance Computing with Modelling and Simulation in order to store, compute, analyse, and visualise large data sets in science and engineering. Funded by the European Commission, cHiPSet has provided a dynamic trans-European forum for their members and distinguished guests to openly discuss novel perspectives and topics of interests for these two communities. This cHiPSet compendium presents a set of selected case studies related to healthcare, biological data, computational advertising, multimedia, finance, bioinformatics, and telecommunications