Showing papers in "Current Opinion in Toxicology in 2019"

TL;DR: This review highlights the differences between Cr(VI) and Cr(III) from a chemical and toxicological perspective, describes short-comings in nutritional research of Cr( III), and explains the multiple mechanisms by which Cr( VI) is involved in the process of carcinogenesis.

TL;DR: Characteristics and limitations of 2D and 3D monoculture and coculture human liver cell models are reviewed to inform selection of experimental test systems depending on the toxicological question to be addressed and to promote the further development of in-vitro approaches that address existing technological gaps.

TL;DR: This work discusses study design considerations for HTTr concentration-response screening and presents a framework for the use of HTTr-based biological pathway-altering concentrations (BPACs) in a screening-level, risk-based chemical prioritization approach.

TL;DR: A battery of translational biomarkers for measuring the antioxidant, antimutagenic and antitoxic capacities of plant compounds in three levels are proposed and seem to be suitable surrogate endpoints in the effort to extrapolate in-vitro evidence to in vivo models.

TL;DR: This review focuses on the role of extracellular redox environment in bleomycin toxicity, with attention to the generation ofextracellular ROS, alterations in the redox state of extracllular thiols, and the central role of the extrace cellular isoform of superoxide dismutase in the development of bleomyin induced injury and fibrosis.

TL;DR: The computational exposure tools reviewed here are oriented toward ‘high-throughput’ application, that is, they are suitable for dealing with the thousands of chemicals in commerce with limited sources of chemical exposure information.

TL;DR: The article reviews oxidative stress metabolites in plants and their use as biomarkers in ecotoxicology and an overview of the use of microalgal oxidative stress biomarkers for the study of toxicity mechanisms of common xenobiotics is given.

TL;DR: Until the authors have a better understanding of adverse outcome pathways, it is suggested that grouping of chemicals for mixture risk assessment be based on integrated in vivo and in-vitro data, read-across as well as computational methods such as QSAR models or integrative systems biology.

TL;DR: The physicochemical properties and mechanisms associated with ENM-driven oxidative stress are reviewed and the need for research investigating effects on the redox proteome that may lead to cellular dysfunction at low or chronic doses of ENMs is discussed.

TL;DR: Polychlorinated biphenyls have been associated with abnormal liver enzymes and suspected nonalcoholic fatty liver disease (NAFLD) in cohort studies and mechanisms included the disruption of phosphoprotein signaling resulting in altered nuclear receptor function.

TL;DR: Adverse outcome pathways (AOPs) are pragmatic tools in toxicology and risk assessment with broad potential to serve a number of purposes pertinent to safety assessment of chemicals, such as the establishment of quantitative structure–activity relationships, the development of novel in vitro toxicity screening tests, and the elaboration of prioritization strategies.

TL;DR: There is evidence that e-cigs may be harmful to early life development and that the use of e-Cigs should be avoided during pregnancy, and the results of these studies support the need for immediate action.

TL;DR: Overproduction of biogenic aldehydes is a hypothesized factor in neurodegeneration; preventing their formation or scavenging may provide means for neuroprotection.

TL;DR: A model for quantitative prediction of developmental vascular toxicity from ToxCast HTS data is reviewed and results boost confidence in the capacity to predict adverse developmental outcomes from HTS in vitro data and model computational dynamics for in silico reconstruction of developmental systems biology.

TL;DR: This review attempts to highlight the hypothetical roles of Nrf2 in the incidence of nonalcoholic fatty liver disease and provides recommendations on therapeutic strategies of NRF2 activators in NAFLD, including use in the proper phase of the disease for the greatest impact.

TL;DR: Single-cell systems toxicology can provide a wealth of information to elucidate cell-specific alterations and response trajectories, detect points-of-departure, map and develop dynamical models of toxicity pathways.

TL;DR: Inorganic arsenic in the drinking water is a human carcinogen (bladder, lung, and skin), and anticipated drinking water exposures of 50–150 μg/L exceed a tissue concentration of >0.1 μM in humans.

TL;DR: It is proposed that the intestinal microbiota plays a key role in chemical toxicity, which is typically overlooked in existing approaches for risk assessment, and factors such as animal provider, batch/litter differences, and co-caging may significantly influence the outcome of toxicity evaluations based on rodent experiments.

TL;DR: In this current opinion, recent studies and approaches relating cellular mechanisms of lipid peroxidation to the pathogenesis of alcoholic liver disease are highlighted.

TL;DR: This work constructs a framework around the confidence in identification of metabolites and molecular pathways and map multiple toxicometabolomics studies to this framework, revealing that few studies achieve the highest level of confidence defined by the Metabolomics Standards Initiative.

TL;DR: This review will describe NGS-based technologies, demonstrate how they can be used as tools for target discovery in tissue and blood, and suggest how they might be applied for risk assessment.

TL;DR: It is believed the integration of systems biology principles, network science, systems toxicology, and the exposome can help synthesize the complex interplay between the environment and biology.

TL;DR: The concept of ontologies is introduced and the vision for computationally enabled semantic toxicology is presented, presenting the utility of adopting ontologies and semantic methods to bring disparate data into a scientifically meaningful context to drive novel scientific insights.

TL;DR: Tuning expectations of NAM performance to an understanding of the reproducibility and variability, both of traditional approaches and NAM approaches, provides a path for the adopted NAMs as alternatives in screening chemicals for risk.

TL;DR: Neurosteroids are discovered as next-generation anticonvulsants superior to midazolam for the treatment of OP poisoning and represent rational anticonVulsants for OP intoxication, even when given late after exposure.

TL;DR: The need to evaluate surrogate and target tissues in the field of toxicoepigenetics is highlighted as the National Institute of Environmental Health Sciences multi-phased Toxicant Exposure and Response by Genomic and Epigenomic Regulators of Transcription consortia make headway, and the emergence of non-coding RNA biomarkers are discussed.

TL;DR: The scientific literature is reviewed, highlighting the potential role of genetic polymorphisms in the enhancement of pesticide induced-oxidative stress and suggesting that some workers could be at higher risk of developing diseases because of these genetic conditions which today are not taken into account in health surveillance programs.

TL;DR: Understanding microbiome-host arsenic-interactions will foster development of novel targeted strategies to relieve or prevent arsenic-associated pathologies, as well as assess the interplay between the two.

TL;DR: The advantages of the use of systems biology tools in chemical risk assessment, as well as the challenges they present, such as model over-parametrisation in quantitative modelling, data gap management in poorly studied substances and the lack of expertise in bridging the new approaches to regulatory levels are discussed.

TL;DR: An overview of the EU-ToxRisk project, its aims and approach, and the methodologies that are being used is provided.