Retrospective Detection of from Snake Moults Collected in Bieszczady Mountains, Poland.

, the causative agent of ophidiomycosis, poses a potential threat to wild snakes worldwide. This study aimed to retrospectively investigate the prevalence of in archived snake moults collected from the San River Valley in the Bieszczady Mountains, Poland, from 2010 to 2012. Using qPCR for detection and conventional PCR for clade characterisation, we analysed 58 moults and one road-killed specimen of and .

A Guide to the Clinical Management of Snakebite in Italy.

The genus encompasses most species of medically significant venomous snakes of Europe, with Italy harbouring four of them. Envenomation by European vipers can result in severe consequences, but underreporting and the absence of standardised clinical protocols hinder effective snakebite management. This study provides an updated, detailed set of guidelines for the management and treatment of snakebite tailored for Italian clinicians.

TKPlate 1.0: An Open-access platform for toxicokinetic and toxicodynamic modelling of chemicals to implement new approach methodologies in chemical risk assessment.

This publication is linked to the following EFSA Supporting Publications articles: http://onlinelibrary.wiley.com/doi/10.

An in silico insight on the mechanistic aspects of gelsenicine toxicity: A reverse screening study pointing to the possible involvement of acetylcholine binding receptor.

Gelsedine-type alkaloids are highly toxic plant secondary metabolites produced by shrubs belonging to the Gelsemium genus. Gelsenicine is one of the most concerning gelsedine-type alkaloids with a lethal dose lower than 1 mg/Kg in mice. Several reported episodes of poisoning in livestock and fatality cases in humans due to the usage of Gelsemium plants extracts were reported.

Exploring Dimensionality Reduction Techniques for Deep Learning Driven QSAR Models of Mutagenicity.

Dimensionality reduction techniques are crucial for enabling deep learning driven quantitative structure-activity relationship (QSAR) models to navigate higher dimensional toxicological spaces, however the use of specific techniques is often arbitrary and poorly explored. Six dimensionality techniques (both linear and non-linear) were hence applied to a higher dimensionality mutagenicity dataset and compared in their ability to power a simple deep learning driven QSAR model, following grid searches for optimal hyperparameter values. It was found that comparatively simpler linear techniques, such as principal component analysis (PCA), were sufficient for enabling optimal QSAR model performances, which indicated that the original dataset was at least approximately linearly separable (in accordance with Cover's theorem).

The VEGA Tool to Check the Applicability Domain Gives Greater Confidence in the Prediction of In Silico Models.

A sound assessment of in silico models and their applicability domain can support the use of new approach methodologies (NAMs) in chemical risk assessment and requires increasing the users' confidence in this approach. Several approaches have been proposed to evaluate the applicability domain of such models, but their prediction power still needs a thorough assessment. In this context, the VEGA tool capable of assessing the applicability domain of in silico models is examined for a range of toxicological endpoints.

Pilot survey reveals ophidiomycosis in dice snakes Natrix tessellata from Lake Garda, Italy.

Ophidiomycosis is an emerging infectious disease caused by the fungus Ophidiomyces ophidiicola (Oo). To date, Oo presence or associated disease condition has been recorded in wild and/or captive snakes from North America, Europe, Asia and Australia, but the data is still scarce outside the Nearctic. Although Italy is a country with a high snake biodiversity in the European panorama, and animals with clinical signs compatible with Oo infection have been documented, to date no investigations have reported the disease in the wild.

A computational study on the biotransformation of alkenylbenzenes by a selection of CYPs: Reflections on their possible bioactivation.

Alkenylbenzenes are aromatic compounds found in several vegetable foods that can cause genotoxicity upon bioactivation by members of the cytochrome P450 (CYP) family, forming 1'-hydroxy metabolites. These intermediates act as proximate carcinogens and can be further converted into reactive 1'-sulfooxy metabolites, which are the ultimate carcinogens responsible for genotoxicity. Safrole, a member of this class, has been banned as a food or feed additive in many countries based on its genotoxicity and carcinogenicity.

A Computational Inter-Species Study on Safrole Phase I Metabolism-Dependent Bioactivation: A Mechanistic Insight into the Study of Possible Differences among Species.

Safrole, a 162.2 Da natural compound belonging to the alkenylbenzenes class, is classified as a possible carcinogen to humans by IARC (group IIB) and has proven to be genotoxic and carcinogenic to rodents. Despite its use as a food or feed additive, it is forbidden in many countries due to its documented toxicity; yet, it is still broadly present within food and feed and is particularly abundant in spices, herbs and essential oils.

The use of new approach methodologies for the environmental risk assessment of food and feed chemicals.

New Approach Methodologies (NAMs) provide tools for supporting both human and environmental risk assessment (HRA and ERA). This short review provides recent insights regarding the use of NAMs in ERA of food and feed chemicals. We highlight the usefulness of tiered methods supporting weight-of-evidence approaches in relation to problem formulation (i.

Risk Assessment of Combined Exposure to Multiple Chemicals at the European Food Safety Authority: Principles, Guidance Documents, Applications and Future Challenges.

Human health and animal health risk assessment of combined exposure to multiple chemicals use the same steps as single-substance risk assessment, namely problem formulation, exposure assessment, hazard assessment and risk characterisation. The main unique feature of combined RA is the assessment of combined exposure, toxicity and risk. Recently, the Scientific Committee of the European Food Safety Authority (EFSA) published two relevant guidance documents.

Perfluoroalkyl substances (PFASs) are substrates of the renal human organic anion transporter 4 (OAT4).

Poly- and perfluoroalkyl substances (PFASs) are omnipresent in the environment and have been shown to accumulate in humans. Most PFASs are not biotransformed in animals and humans, so that elimination is largely dependent on non-metabolic clearance via bile and urine. Accumulation of certain PFASs in humans may relate to their reabsorption from the pre-urine by transporter proteins in the proximal tubules of the kidney, such as URAT1 and OAT4.

Congeners-Specific Intestinal Absorption Of Microcystins In An 3D Human Intestinal Epithelium: The Role Of Influx/Efflux Transporters.

Microcystins constitute a group of over 200 variants and are increasingly considered as emerging toxins in food and feed safety, particularly with regards to sea-food and fish consumption. Toxicity of MCs is congener-specific, being characterised by different acute potencies, likely related to the differential activity of metabolic enzymes and transporters proteins involved in their cellular uptake. However, the active transport of MCs across intestinal membranes has not been fully elucidated.

Cardiotoxicity of Chemical Substances: An Emerging Hazard Class.

(1) Background: Human health risks and hazards from chemical substances are well regulated internationally. However, cardiotoxicity, is not defined as a stand-alone hazard and therefore there are no defined criteria for the classification of substances as cardiotoxic. Identifying and regulating substances that cause cardiovascular adverse effects would undoubtedly strengthen the national health systems.

Risk assessment of uptake of trace elements through consumption of cereals: a pilot study in Yerevan, Armenia.

The study aimed to assess the dietary exposure and related human health risks associated with trace elements through the intake of staple cereals, including buckwheat, rice, and emmer. The contents of Lead (Pb), Cadmium (Cd), Mercury (Hg), Nickel (Ni), Molybdenum (Mo), Iron (Fe), and Copper (Cu) were determined using Atomic Absorption Spectrometry. Cereal consumption data were obtained through a Semi-Quantitative Food Frequency Questionnaire amongst the Yerevan adult population.

Principles and framework for assessing the risk of bias for studies included in comparative quantitative environmental systematic reviews.

The internal validity of conclusions about effectiveness or impact in systematic reviews, and of decisions based on them, depends on risk of bias assessments being conducted appropriately. However, a random sample of 50 recently-published articles claiming to be quantitative environmental systematic reviews found 64% did not include any risk of bias assessment, whilst nearly all that did omitted key sources of bias. Other limitations included lack of transparency, conflation of quality constructs, and incomplete application of risk of bias assessments to the data synthesis.

A regression-based QSAR-model to predict acute toxicity of aromatic chemicals in tadpoles of the Japanese brown frog (Rana japonica): Calibration, validation, and future developments to support risk assessment of chemicals in amphibians.

Amphibian populations are undergoing a global decline worldwide. Such decline has been attributed to their unique physiology, ecology, and exposure to multiple stressors including chemicals, temperature, and biological hazards such as fungi of the Batrachochytrium genus, viruses such as Ranavirus, and habitat reduction. There are limited toxicity data for chemicals available for amphibians and few quantitative structure-activity relationship (QSAR) models have been developed and are publicly available.

A Computational Understanding of Inter-Individual Variability in CYP2D6 Activity to Investigate the Impact of Missense Mutations on Ochratoxin A Metabolism.

Cytochrome P-450 (CYP) enzymes have a key role in the metabolism of xenobiotics of food origin, and their highly polymorphic nature concurs with the diverse inter-individual variability in the toxicokinetics (TK) and toxicodynamics (TD) of food chemicals. Ochratoxin A is a well-known mycotoxin which contaminates a large variety of food and is associated with food safety concerns. It is a minor substrate of CYP2D6, although the effects of CYP2D6 polymorphisms on its metabolism may be overlooked.

Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks.

The workshop titled “Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks” was co-organized by the Evidence-based Toxicology Collaboration and the European Food Safety Authority (EFSA) and hosted by EFSA at its headquarters in Parma, Italy on October 2 and 3, 2019. The goal was to explore integration of systematic review with mechanistic evidence evaluation. Participants were invited to work on concrete products to advance the exploration of how evidence-based approaches can support the development and application of adverse outcome pathways (AOP) in chemical risk assessment.

In Silico Methods for Environmental Risk Assessment: Principles, Tiered Approaches, Applications, and Future Perspectives.

This chapter aims to introduce the reader to the basic principles of environmental risk assessment of chemicals and highlights the usefulness of tiered approaches within weight of evidence approaches in relation to problem formulation i.e., data availability, time and resource availability.

QSAR models for soil ecotoxicity: Development and validation of models to predict reproductive toxicity of organic chemicals in the collembola Folsomia candida.

Soil pollution is a critical environmental challenge: the substances released in the soil can adversely affect humans and the ecosystem. Several bioassays were developed to investigate the soil ecotoxicity of chemicals with soil microbes, plants, invertebrates and vertebrates. The 28-day collembolan reproduction test with the springtail Folsomia candida is a recently introduced bioassay described by OECD guideline 232.

Investigating the interaction between organic anion transporter 1 and ochratoxin A: An in silico structural study to depict early molecular events of substrate recruitment and the impact of single point mutations.

Organic anion transporters (OATs) belong to a subgroup of the solute carrier 22 transporter family. OATs have a central role in xenobiotic disposition affecting the toxicokinetics of its substrates and inter-individual differences in their expression, activity and function impact both toxicokinetics and toxicodynamics. Amongst OATs, OAT1 (solute carrier family 22 member 6) is involved in the urinary excretion of many xenobiotics bringing substrates into renal proximal tubular cells which can then be secreted across the apical membrane into the tubule lumen.

OpenCYP: An open source database exploring human variability in activities and frequencies of polymophisms for major cytochrome P-450 isoforms across world populations.

The open source database "OpenCYP database" has been developed based on the results of extensive literature searches from the peer-reviewed literature. OpenCYP provides data on human variability on baseline of activities and polymophism frequencies for selected cytochrome P-450 isoforms (CYP1A2, CYP2A6, CYP2D6, CYP3A4/3A5 and CYP3A7) in healthy adult populations from world populations. CYP enzymatic activities were generally expressed as the metabolic ratio (MR) between an unchanged probe drug and its metabolite(s) in urine or plasma measured in healthy adults.

Derivation of a Human In Vivo Benchmark Dose for Perfluorooctanoic Acid From ToxCast In Vitro Concentration-Response Data Using a Computational Workflow for Probabilistic Quantitative In Vitro to In Vivo Extrapolation.

A computational workflow which integrates physiologically based kinetic (PBK) modeling, global sensitivity analysis (GSA), approximate Bayesian computation (ABC), and Markov Chain Monte Carlo (MCMC) simulation was developed to facilitate quantitative to extrapolation (QIVIVE). The workflow accounts for parameter and model uncertainty within a computationally efficient framework. The workflow was tested using a human PBK model for perfluorooctanoic acid (PFOA) and high throughput screening (HTS) concentration-response data, determined in a human liver cell line, from the ToxCast/Tox21 database.