Unravelling drug-induced hepatic steatosis: Clinical sub-phenotypes, outcome prediction, and identification of high-concern drugs and hazardous chemical attributes.

Background: Drug-induced liver injury (DILI) is a rare but serious adverse drug reaction with a wide range of clinical presentations. While three major DILI phenotypes-hepatocellular, cholestatic, and mixed-are well established, other injury patterns such as steatosis-associated DILI (DIS) are harder to identify and remain underexplored. Existing limited evidence suggests that steatosis is frequent among DILI patients, yet this subtype and its causative drugs have not been systematically characterized in large patient cohorts.

ExtractPDF: A data extraction tool for scientific papers applied to a systematic scoping review in public health.

Background And Objectives: Systematic reviews are widely used to identify the evidence and get an overview of the available knowledge for various questions related to public health and medical topics. They can provide a summary of all the available data and can be used to make knowledge-based decisions about policy, practice, and academic research. The conduct of systematic reviews can often be time-consuming and costly.

Guidance on minimum information requirements (MIR) from designing to reporting human biomonitoring (HBM).

Human biomonitoring (HBM) provides an integrated chemical exposures assessment considering all routes and sources of exposure. The accurate interpretation and comparability of biomarkers of exposure and effect depend on harmonized, quality-assured sampling, processing, and analysis. Currently, the lack of broadly accepted guidance on minimum information required for collecting and reporting HBM data, hinders comparability between studies.

Chemical risk analysis competence in the Nordics is at stake.

Toxicology-related experts are on a daily basis working with the safety assessment of chemicals for human health and the environment, providing knowledge applied for management and regulation of chemicals. The field of toxicology is undergoing continuous transition away from traditional safety evaluation studies in experimental animals to application of new approach methodologies (NAMs), the use of omics-related technologies, and concepts like next-generation risk assessment. This requires expertise in the new technologies but does not dismiss the need of knowledge for interpretation of in vivo studies and full understanding of chemical exposure data.

Hazard characterization of the mycotoxins enniatins and beauvericin to identify data gaps and improve risk assessment for human health.

Enniatins (ENNs) and beauvericin (BEA) are cyclic hexadepsipeptide fungal metabolites which have demonstrated antibiotic, antimycotic, and insecticidal activities. The substantial toxic potentials of these mycotoxins are associated with their ionophoric molecular properties and relatively high lipophilicities. ENNs occur extensively in grain and grain-derived products and are considered a food safety issue by the European Food Safety Authority (EFSA).

Climate change and health in the Arctic.

Aim: Adverse human-driven environmental change, including the climate, is having an increasing impact on the Arctic environment and its ecosystems. There has been immense interest in understanding the health risks related to climate change in the Arctic region. In this article, we review recent evidence related to climate change and its impacts on the health of the Arctic population.

AOP-networkFinder-a versatile tool for the reconstruction and visualization of Adverse Outcome Pathway networks from AOP-Wiki.

Motivation: The Adverse Outcome Pathways (AOP)-Wiki, a knowledge database for AOPs, requires an efficient way to present an overview of its content for the reconstruction of networks by experts in a given domain. We have developed the AOP-networkFinder, a user-friendly tool that retrieves AOPs of interest, allows network generation and cleaning, and finally visualizes networks built around the retrieved AOPs. Our tool constructs AOP networks by connecting AOPs that use the same Key Events (KEs) in a versatile but controlled manner.

Towards a risk assessment framework for micro- and nanoplastic particles for human health.

Background: Human exposure to micro- and nanoplastic particles (MNPs) is inevitable but human health risk assessment remains challenging for several reasons. MNPs are complex mixtures of particles derived from different polymer types, which may contain plenty of additives and/or contaminants. MNPs cover broad size distributions and often have irregular shapes and morphologies.

Transcriptomic characterization of 2D and 3D human induced pluripotent stem cell-based in vitro models as New Approach Methodologies for developmental neurotoxicity testing.

The safety and developmental neurotoxicity (DNT) potential of chemicals remain critically understudied due to limitations of current in vivo testing guidelines, which are low throughput, resource-intensive, and hindered by species differences that limit their relevance to human health. To address these issues, robust New Approach Methodologies (NAMs) using deeply characterized cell models are essential. This study presents the comprehensive transcriptomic characterization of two advanced human-induced pluripotent stem cell (hiPSC)-derived models: a 2D adherent and a 3D neurosphere model of human neural progenitor cells (hiNPCs) differentiated up to 21 days.

Immune cell profiles associated with human exposure to perfluorinated compounds (PFAS) suggest changes in natural killer, T helper, and T cytotoxic cell subpopulations.

Per- and polyfluoroalkyl substances (PFAS) constitutes a group of highly persistent man-made substances. Recent evidence indicates that PFAS negatively impact the immune system. However, it remains unclear how different PFAS are associated with alterations in circulating leukocyte subpopulations.

Accessible methods and tools to estimate chemical exposure in humans to support risk assessment: A systematic scoping review.

Exposure assessment is a crucial component of environmental health research, providing essential information on the potential risks associated with various chemicals. A systematic scoping review was conducted to acquire an overview of accessible human exposure assessment methods and computational tools to support and ultimately improve risk assessment. The systematic scoping review was performed in Sysrev, a web platform that introduces machine learning techniques into the review process aiming for increased accuracy and efficiency.

Novel clinical phenotypes, drug categorization, and outcome prediction in drug-induced cholestasis: Analysis of a database of 432 patients developed by literature review and machine learning support.

Background: Serum transaminases, alkaline phosphatase and bilirubin are common parameters used for DILI diagnosis, classification, and prognosis. However, the relevance of clinical examination, histopathology and drug chemical properties have not been fully investigated. As cholestasis is a frequent and complex DILI manifestation, our goal was to investigate the relevance of clinical features and drug properties to stratify drug-induced cholestasis (DIC) patients, and to develop a prognosis model to identify patients at risk and high-concern drugs.

Hazard characterization of Alternaria toxins to identify data gaps and improve risk assessment for human health.

Fungi of the genus Alternaria are ubiquitous plant pathogens and saprophytes which are able to grow under varying temperature and moisture conditions as well as on a large range of substrates. A spectrum of structurally diverse secondary metabolites with toxic potential has been identified, but occurrence and relative proportion of the different metabolites in complex mixtures depend on strain, substrate, and growth conditions. This review compiles the available knowledge on hazard identification and characterization of Alternaria toxins.

Dietary intake of acrylamide in the Norwegian EuroMix biomonitoring study: Comparing probabilistic dietary estimates with haemoglobin adduct measurements.

Acrylamide is a probable human carcinogen with widespread exposure via food. The present study compared acrylamide intake measurements obtained from haemoglobin adduct levels and self-registered dietary consumption data in a group of 144 Norwegian healthy adults. Acrylamide adducts to N-terminal valine in haemoglobin were measured and used to estimate the intake via the internal dose approach which showed a median (interquartile range) of 0.

Transcriptional analysis in peripheral blood cells of individuals with elevated phthalate exposure - Results of the EuroMix study.

Exposure to phthalates is widespread in Europe. Phthalates are considered endocrine disrupting compounds and are classified as toxic for reproduction. However how phthalates affect the transcriptome in humans remains largely unknown.

Suspected gut barrier disruptors and development of food allergy: Adjuvant effects and early immune responses.

Food allergy is an increasing public health challenge worldwide. It has recently been hypothesized that the increase in exposure to intestinal epithelial barrier-damaging biological and chemical agents contribute to this development. In animal models, exposure to adjuvants with a food allergen has been shown to promote sensitization and development of food allergy, and barrier disrupting capacities have been suggested to be one mechanism of adjuvant action.

Exposure to persistent organic pollutants alters the serum metabolome in non-obese diabetic mice.

Introduction: Autoimmune disorders such as type 1 diabetes (T1D) are believed to be caused by the interplay between several genetic and environmental factors. Elucidation of the role of environmental factors in metabolic and immune dysfunction leading to autoimmune disease is not yet well characterized.

Objectives: Here we investigated the impact of exposure to a mixture of persistent organic pollutants (POPs) on the metabolome in non-obese diabetic (NOD) mice, an experimental model of T1D.

Developing human biomonitoring as a 21st century toolbox within the European exposure science strategy 2020-2030.

Human biomonitoring (HBM) is a crucial approach for exposure assessment, as emphasised in the European Commission's Chemicals Strategy for Sustainability (CSS). HBM can help to improve chemical policies in five major key areas: (1) assessing internal and aggregate exposure in different target populations; 2) assessing exposure to chemicals across life stages; (3) assessing combined exposure to multiple chemicals (mixtures); (4) bridging regulatory silos on aggregate exposure; and (5) enhancing the effectiveness of risk management measures. In this strategy paper we propose a vision and a strategy for the use of HBM in chemical regulations and public health policy in Europe and beyond.

Developmental neurotoxicity of acrylamide and its metabolite glycidamide in a human mixed culture of neurons and astrocytes undergoing differentiation in concentrations relevant for human exposure.

Neural stem cells (NSCs) derived from human induced pluripotent stem cells were used to investigate effects of exposure to the food contaminant acrylamide (AA) and its main metabolite glycidamide (GA) on key neurodevelopmental processes. Diet is an important source of human AA exposure for pregnant women, and AA is known to pass the placenta and the newborn may also be exposed through breast feeding after birth. The NSCs were exposed to AA and GA (1 ×10 - 3 ×10 M) under 7 days of proliferation and up to 28 days of differentiation towards a mixed culture of neurons and astrocytes.

Lipoprotein profiles associated with exposure to poly- and perfluoroalkyl substances (PFASs) in the EuroMix human biomonitoring study.

Exposure to per- and polyfluoroalkyl substances (PFASs) is associated with increased blood cholesterol. Although elevated cholesterol is a well-established risk factor for cardiovascular diseases (CVD), it is not clear whether PFASs affect this risk. Lipoprotein subclasses are emerging biomarkers for disease risk and lipoprotein profiling may provide an insight to physiological implications of PFAS exposure.