A conceptual framework for landscape-based environmental risk assessment (ERA) of pesticides.

While pesticide use is subject to strict regulatory oversight worldwide, it remains a main concern for environmental protection, including biodiversity conservation. This is partly due to the current regulatory approach that relies on separate assessments for each single pesticide, crop use, and non-target organism group at local scales. Such assessments tend to overlook the combined effects of overall pesticide usage at larger spatial scales.

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.

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.

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.

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.

Scientific Opinion of the Scientific Panel on Plant Protection Products and their Residues (PPR Panel) on testing and interpretation of comparative metabolism studies.

EFSA asked the Panel on Plant Protection Products and their residues to deliver a Scientific Opinion on testing and interpretation of comparative metabolism studies for both new active substances and existing ones. The main aim of comparative metabolism studies of pesticide active substances is to evaluate whether all significant metabolites formed in the human test system, as a surrogate of the situation, are also present at comparable level in animal species tested in toxicological studies and, therefore, if their potential toxicity has been appropriately covered by animal studies. The studies may also help to decide which animal model, with regard to a particular compound, is the most relevant for humans.

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.

A systems-based approach to the environmental risk assessment of multiple stressors in honey bees.

The European Parliament requested EFSA to develop a holistic risk assessment of multiple stressors in honey bees. To this end, a systems-based approach that is composed of two core components: a monitoring system and a modelling system are put forward with honey bees taken as a showcase. Key developments in the current scientific opinion (including systematic data collection from sentinel beehives and an agent-based simulation) have the potential to substantially contribute to future development of environmental risk assessments of multiple stressors at larger spatial and temporal scales.

Sourcing data on chemical properties and hazard data from the US-EPA CompTox Chemicals Dashboard: A practical guide for human risk assessment.

For the past six decades, human health risk assessment of chemicals has relied on in vivo data from human epidemiological and experimental animal toxicological studies to inform the derivation of non-cancer toxicity values. The ongoing evolution of this risk assessment paradigm in an environmental landscape of data-poor chemicals has highlighted the need to develop and implement non-testing methods, so-called New Approach Methodologies (NAMs). NAMs include a growing number of in silico and in vitro data streams designed to inform hazard properties of chemicals, including kinetics and dynamics at different levels of biological organization, environmental fate and transport, and exposure.

Inter-phenotypic differences in CYP2C9 and CYP2C19 metabolism: Bayesian meta-regression of human population variability in kinetics and application in chemical risk assessment.

Quantifying variability in pharmacokinetics (PK) and toxicokinetics (TK) provides a science-based approach to refine uncertainty factors (UFs) for chemical risk assessment. In this context, genetic polymorphisms in cytochromes P450 (CYPs) drive inter-phenotypic differences and may result in reduction or increase in metabolism of drugs or other xenobiotics. Here, an extensive literature search was performed to identify PK data for probe substrates of the human polymorphic isoforms CYP2C9 and CYP2C19.

[Corrigendum] What is considered cardiotoxicity of anthracyclines in animal studies.

Subsequently to the publication of this paper, the authors have realized that the name of the seventh listed author, Dimitrios Stagos, was spelt incorrectly (it appeared as 'Stagkos' in print). The corrected author list is shown above. The authors regret that the name of the seventh author on the paper was spelt incorrectly, and apologize to the readers for any inconvenience caused.

Phosmet bioactivation by isoform-specific cytochrome P450s in human hepatic and gut samples and metabolic interaction with chlorpyrifos.

Data on the bioactivation of Phosmet (Pho), a phthalimide-derived organophosphate pesticide (OPT), to the neurotoxic metabolite Phosmet-oxon (PhOx) in human are not available. The characterization of the reaction in single human recombinant CYPs evidenced that the ranking of the intrinsic clearances was: 2C18>2C19>2B6>2C9>1A1>1A2>2D6>3A4>2A6. Considering the average human hepatic content, CYP2C19 contributed for the great majority (60%) at relevant exposure concentrations, while CYP2C9 (33%) and CYP3A4 (31%) were relevant at high substrate concentration.

The using of the Index of Ideality of Correlation (IIC) to improve predictive potential of models of water solubility for pesticides.

Models for water solubility of pesticides suggested in this manuscript are important data from point of view of ecologic engineering. The Index of Ideality of Correlation (IIC) of groups of quantitative structure-property relationships (QSPRs) for water solubility of pesticides related to the calibration sets was used to identify good in silico models. This comparison confirmed the high IIC set provides better statistical quality of the model for the validation set.