COT Statement on the interaction of caffeine and alcohol and their combined effects on health and behaviour

Alcohol mixed with high-caffeine energy drinks are becoming more popular. The COT was asked to review the evidence on a potential interaction between these two biologically active substances and conclude on whether they have a combined effect on health and behaviour

Toxicity

In research on online comments on social media platforms, different terms are widely used to describe comments that are hateful or disrespectful and thereby poison a discussion. This chapter takes a theoretical perspective on the term toxicity and related research in the field of computer science. More specifically, it explains the usage of the term and why its exact interpretation depends on the platform in question. Further, the article discusses the advantages of toxicity over other terms and provides an overview of the available toxic comment datasets. Finally, it introduces the concept of engaging comments as the counterpart of toxic comments, leading to a task that is complementary to the prevention and removal of toxic comments: the fostering and highlighting of engaging comments

Study of Acute Toxicity of a New Veterinary Drug for Inttrammary Introduction

Preclinical studies of veterinary medicinal products are important and compulsory studies in the development of new dosage forms. The aim of preclinical research is to determine the toxic effect and therapeutic efficacy of the test substance-the future dosage form, its effect on the body\u27s basic systems, as well as the identification of possible side effects.This work is part of the research on the development of the composition and technology of the veterinary drug - a solution for intramammary application, conventionally called "Argocide", intended for the treatment of mastitis in cattle.A study of the acute toxicity of the intramammary veterinary drug was carried out in experiments on white rats of both sexes, according to the requirements for potential medicines. The establishment of the value of the average lethal dose (LD50) of the veterinary drug "Argocide" with intramuscular single administration to white mature rats is impossible due to the absence of animal death even when the drug is administered at doses exceeding 5.0 ml/kg. This experiment allows the veterinary preparation "Argocide" to be classified as practically non-toxic compounds (V class).The analysis of the results of the conducted studies indicates the relative harmlessness of the potential drug for veterinary medicine and allows us to foresee that the "Argocide" preparation can be classified as low-risk substances, which justifies the expediency of its further study and introduction into practice

Toxicity of Flow Line, Durafill VS, and Dycal to Dental Pulp Cells: Effects of Growth Factors

Introduction The objective was to determine the effects of growth factor treatment on dental pulp cell sensitivity to toxicity of 2 composite restoration materials, Flow Line and Durafill VS, and a calcium hydroxide pulp capping material, Dycal. Methods Toxicity of the dental materials to cultures of primary dental pulp cells was determined by the MTT metabolism assay. The ability of 6 different growth factors to influence the toxicity was tested. Results A 24-hour exposure to either Flow Line or Durafill VS caused approximately 40% cell death, whereas Dycal exposure caused approximately 80% cell death. The toxicity of Flow Line and Durafill VS was mediated by oxidative stress. Four of the growth factors tested (bone morphogenetic protein [BMP]-2, BMP-7, epidermal growth factor [EGF], and transforming growth factor [TGF]-β) decreased the basal MTT values while making the cells resistant to Flow Line and Durafill VS toxicity except BMP-2, which made the cells more sensitive to Flow Line. Treatment with fibroblast growth factor-2 caused no change in basal MTT metabolism, prevented the toxicity of Durafill VS, but increased the toxicity of Flow Line. Treatment with insulin-like growth factor-I (IGF-I) increased basal MTT metabolism and made the cells resistant to Flow Line and Durafill VS toxicity. None of the growth factors made the cells resistant to Dycal toxicity. Conclusions The results indicated that growth factors can be used to alter the sensitivity of dental pulp cells to commonly used restoration materials. The growth factors BMP-7, EGF, TGF-β, and IGF-I provided the best profile of effects, making the cells resistant to both Flow Line and Durafill VS toxicity

Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients

Suppression of polyglutamine toxicity by a Drosophila homolog of myeloid leukemia factor 1

The toxicity of an abnormally long polyglutamine [poly(Q)] tract within specific proteins is the molecular lesion shared by Huntington's disease (HD) and several other hereditary neurodegenerative disorders. By a genetic screen in Drosophila, devised to uncover genes that suppress poly(Q) toxicity, we discovered a Drosophila homolog of human myeloid leukemia factor 1 (MLF1). Expression of the Drosophila homolog (dMLF) ameliorates the toxicity of poly(Q) expressed in the eye and central nervous system. In the retina, whether endogenously or ectopically expressed, dMLF co-localized with aggregates, suggesting that dMLF alone, or through an intermediary molecular partner, may suppress toxicity by sequestering poly(Q) and/or its aggregates

Hypersensitivity to Pegylated E.coli asparaginase as first-line treatment in contemporary paediatric acute lymphoblastic leukaemia protocols: a meta-analysis of the Ponte di Legno Toxicity working group

[EN] BACKGROUND: Hypersensitivity reactions to asparaginase challenge its use and occur frequently (30-75%) after native Escherichia Coli (E.coli) asparaginase. Comparison of incidence of allergic reactions to pegylated E.coli asparaginase (PEGasparaginase) across contemporary paediatric acute lymphoblastic leukaemia (ALL) protocols is lacking. METHOD AND PATIENTS: Questionnaires were sent to all members of the international ALL Ponte di Legno Toxicity Working Group. Meta-analyses were conducted to estimate the incidence of three types of hypersensitivity (allergy, allergic-like reaction and silent inactivation). Information on protocol level regarding PEGasparaginase dosing regimen, administration route and use of therapeutic drug monitoring was collected for risk analysis. RESULTS: Newly diagnosedpatients with ALL (n=5880), aged 1-24 years old, were enrolled in seven different upfront ALL protocols using PEGasparaginase as first-line treatment. The incidence of allergic reactions (sum of allergies and allergic-like reactions) [95% confidence interval] was 2% [1%; 3%] during induction and 8% [5%; 11%] during postinduction. Route of administration, number of doses, dosage and number of PEGasparaginase-free weeks did not significantly influence risk of hypersensitivity. Multivariate meta-regression analysis suggests that initiation of PEGasparaginase in postinduction and higher number of PEGasparaginase-free intervals increased the risk for allergic reactions. 9-16% and 23-29% of all hypersensitivities were allergic-like reactions and silent inactivation, respectively. CONCLUSION: The incidence of allergic reactions is lower in protocols using PEGasparaginase as first-line treatment compared with that reported for E.coli asparaginase or PEGasparaginase after E.coli asparaginase. Postinduction phase, a higher number of PEGasparaginase-free intervals, and initiation of PEGasparaginase in postinduction phase are risk factors for allergic reactions. These results are important for planning of PEGasparaginase administrations in future frontline therapy.BSPHO: none. CoALL: none. DCOG: none. DFCI: none. NOPHO: The authors BKA and KS would like to thank the Danish Cancer Society and the Danish Childhood Cancer Society for supporting this study. LAL/SEHOP-PETHEMA: Author ELL would like to thank all involved hospitals for data collection. UKALL: Author AV would like to thank Amy Kirkwood, UKALL 2011 statistician, for collecting the UK data

Toxicity of lunar dust

The formation, composition and physical properties of lunar dust are incompletely characterised with regard to human health. While the physical and chemical determinants of dust toxicity for materials such as asbestos, quartz, volcanic ashes and urban particulate matter have been the focus of substantial research efforts, lunar dust properties, and therefore lunar dust toxicity may differ substantially. In this contribution, past and ongoing work on dust toxicity is reviewed, and major knowledge gaps that prevent an accurate assessment of lunar dust toxicity are identified. Finally, a range of studies using ground-based, low-gravity, and in situ measurements is recommended to address the identified knowledge gaps. Because none of the curated lunar samples exist in a pristine state that preserves the surface reactive chemical aspects thought to be present on the lunar surface, studies using this material carry with them considerable uncertainty in terms of fidelity. As a consequence, in situ data on lunar dust properties will be required to provide ground truth for ground-based studies quantifying the toxicity of dust exposure and the associated health risks during future manned lunar missions.Comment: 62 pages, 9 figures, 2 tables, accepted for publication in Planetary and Space Scienc

Quantitative toxicity prediction using topology based multi-task deep neural networks

The understanding of toxicity is of paramount importance to human health and environmental protection. Quantitative toxicity analysis has become a new standard in the field. This work introduces element specific persistent homology (ESPH), an algebraic topology approach, for quantitative toxicity prediction. ESPH retains crucial chemical information during the topological abstraction of geometric complexity and provides a representation of small molecules that cannot be obtained by any other method. To investigate the representability and predictive power of ESPH for small molecules, ancillary descriptors have also been developed based on physical models. Topological and physical descriptors are paired with advanced machine learning algorithms, such as deep neural network (DNN), random forest (RF) and gradient boosting decision tree (GBDT), to facilitate their applications to quantitative toxicity predictions. A topology based multi-task strategy is proposed to take the advantage of the availability of large data sets while dealing with small data sets. Four benchmark toxicity data sets that involve quantitative measurements are used to validate the proposed approaches. Extensive numerical studies indicate that the proposed topological learning methods are able to outperform the state-of-the-art methods in the literature for quantitative toxicity analysis. Our online server for computing element-specific topological descriptors (ESTDs) is available at http://weilab.math.msu.edu/TopTox/Comment: arXiv admin note: substantial text overlap with arXiv:1703.1095