EFSA's OpenFoodTox: An open source toxicological database on chemicals in food and feed and its future developments.

Since its creation in 2002, the European Food Safety Authority (EFSA) has produced risk assessments for over 5000 substances in >2000 Scientific Opinions, Statements and Conclusions through the work of its Scientific Panels, Units and Scientific Committee. OpenFoodTox is an open source toxicological database, available both for download and data visualisation which provides data for all substances evaluated by EFSA including substance characterisation, links to EFSA's outputs, applicable legislations regulations, and a summary of hazard identification and hazard characterisation data for human health, animal health and ecological assessments. The database has been structured using OECD harmonised templates for reporting chemical test summaries (OHTs) to facilitate data sharing with stakeholders with an interest in chemical risk assessment, such as sister agencies, international scientific advisory bodies, and others. This manuscript provides a description of OpenFoodTox including data model, content and tools to download and search the database. Examples of applications of OpenFoodTox in chemical risk assessment are discussed including new quantitative structure-activity relationship (QSAR) models, integration into tools (OECD QSAR Toolbox and AMBIT-2.0), assessment of environmental footprints and testing of threshold of toxicological concern (TTC) values for food related compounds. Finally, future developments for OpenFoodTox 2.0 include the integration of new properties, such as physico-chemical properties, exposure data, toxicokinetic information; and the future integration within in silico modelling platforms such as QSAR models and physiologically-based kinetic models. Such structured in vivo, in vitro and in silico hazard data provide different lines of evidence which can be assembled, weighed and integrated using harmonised Weight of Evidence approaches to support the use of New Approach Methodologies (NAMs) in chemical risk assessment and the reduction of animal testing.

Predicting acute contact toxicity of pesticides in honeybees (Apis mellifera) through a k-nearest neighbor model.

Ecological risk assessment of plant protection products (PPPs) requires an understanding of both the toxicity and the extent of exposure to assess risks for a range of taxa of ecological importance including target and non-target species. Non-target species such as honey bees (Apis mellifera), solitary bees and bumble bees are of utmost importance because of their vital ecological services as pollinators of wild plants and crops. To improve risk assessment of PPPs in bee species, computational models predicting the acute and chronic toxicity of a range of PPPs and contaminants can play a major role in providing structural and physico-chemical properties for the prioritisation of compounds of concern and future risk assessments. Over the last three decades, scientific advisory bodies and the research community have developed toxicological databases and quantitative structure-activity relationship (QSAR) models that are proving invaluable to predict toxicity using historical data and reduce animal testing. This paper describes the development and validation of a k-Nearest Neighbor (k-NN) model using in-house software for the prediction of acute contact toxicity of pesticides on honey bees. Acute contact toxicity data were collected from different sources for 256 pesticides, which were divided into training and test sets. The k-NN models were validated with good prediction, with an accuracy of 70% for all compounds and of 65% for highly toxic compounds, suggesting that they might reliably predict the toxicity of structurally diverse pesticides and could be used to screen and prioritise new pesticides.

Role of in silico genotoxicity tools in the regulatory assessment of pharmaceutical impurities.

The toxicological assessment of genotoxic impurities is important in the regulatory framework for pharmaceuticals. In this context, the application of promising computational methods (e.g. Quantitative Structure-Activity Relationships (QSARs), Structure-Activity Relationships (SARs) and/or expert systems) for the evaluation of genotoxicity is needed, especially when very limited information on impurities is available. To gain an overview of how computational methods are used internationally in the regulatory assessment of pharmaceutical impurities, the current regulatory documents were reviewed. The software recommended in the guidelines (e.g. MCASE, MC4PC, Derek for Windows) or used practically by various regulatory agencies (e.g. US Food and Drug Administration, US and Danish Environmental Protection Agencies), as well as other existing programs were analysed. Both statistically based and knowledge-based (expert system) tools were analysed. The overall conclusions on the available in silico tools for genotoxicity and carcinogenicity prediction are quite optimistic, and the regulatory application of QSAR methods is constantly growing. For regulatory purposes, it is recommended that predictions of genotoxicity/carcinogenicity should be based on a battery of models, combining high-sensitivity models (low rate of false negatives) with high-specificity ones (low rate of false positives) and in vitro assays in an integrated manner.

The role of the European Chemicals Bureau in promoting the regulatory use of (Q)SAR methods.

Under the proposed REACH (Registration, Evaluation and Authorisation of CHemicals) legislation, (Q)SAR models and grouping methods (chemical categories and read across approaches) are expected to play a significant role in prioritising industrial chemicals for further assessment, and for filling information gaps for the purposes of classification and labelling, risk assessment and the assessment of persistent, bioaccumulative and toxic (PBT) chemicals. The European Chemicals Bureau (ECB), which is part of the European Commission's Joint Research Centre (JRC), has a well-established role in providing independent scientific and technical advice to European policy makers. The ECB also promotes consensus and capacity building on scientific and technical matters among stakeholders in the Member State authorities and industry. To promote the availability and use of (Q)SARs and related estimation methods, the ECB is carrying out a range of activities, including applied research in computational toxicology, the assessment of (Q)SAR models and methods, the development of technical guidance documents and computational tools, and the organisation of training courses. This article provides an overview of ECB activities on computational toxicology, which are intended to promote the development, validation, acceptance and use of (Q)SARs and related estimation methods, both at the European and international levels.

[Ulcerative lichen ruber planus of the feet, associated with complete loss of the nails and cicatricial alopecia of the scalp]. / Lichen ruber planus ulcerativo ai piedi, associato a perdita definitiva delle unghie ed alopecia cicatriziale del capillizio.

An unusual syndrome of lichen planus, characterized by ulcerations confined to the feet, permanent loss of toenails and a cicatricial alopecia of the scalp is reported, related to a 71 years old woman. Only eleven cases identical of this have been described as yet. Skin grafting to the ulcerous surfaces has been the treatment of choice, because offers the opportunity for a lasting therapeutic response.

[Ultrastructural changes in the human nasal respiratory epithelium in hypersensitivity reactions]. / Modificaciones ultraestructurales del epitelio respiratorio nasal humano en reacciones de hipersensibilidad.

In immunoallergic syndromes, the structure of normal respiratory nasal mucous membrane is modified. The epithelial lining (which is responsible for the effectiveness of the mucociliary synergy), is secondarily affected. Its modifications depend, generally, on the severity and chronicity of the clinical case. Normal and pathologic material obtained from inferior turbinate bone (of similar structure and response to the rest of the respiratory nasal mucous membrane) were studied through transmission and scanning electron microscopies, employing both methods as complementary analysis. In normal cases, the presence of different kinds of cells was confirmed. Some additional characteristics about intercellular spaces and junctions as well as the possible role of the above mentioned structures in transudation were also described. In pathologic cases, increasing lesion staging grades could be determined. In the first stage, structural alterations could not be observed despite the existence of functional disturbances (i.e. ciliary dyskinesia and non-synergic motility). In an advanced stage, ciliary abnormalities could be observed with abnormalities in the number, morphology, spatial orientation and distortion in the number of different cell types. With cellular linkage affectation, the severity of the lesion increased and the cells were easily desquamated, giving rise to intercellular spaces which communicated freely with the organ lumen. Finally, in the most severe cases, the epithelial lining was diminished to a monolayer, with complete cellular dissociation and lack of differentiation. This cellular disarrangement allowed free passage of substances in both directions through the monolayer.