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Regulatory toxicology

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https://www.readbyqxmd.com/read/27917502/relationship-between-increasing-concentrations-of-two-carcinogens-and-statistical-image-descriptors-of-foci-morphology-in-the-cell-transformation-assay
#1
Giulia Callegaro, Raffaella Corvi, Susan Salovaara, Chiara Urani, Federico M Stefanini
Cell Transformation Assays (CTAs) have long been proposed for the identification of chemical carcinogenicity potential. The endpoint of these in vitro assays is represented by the phenotypic alterations in cultured cells, which are characterized by the change from the non-transformed to the transformed phenotype. Despite the wide fields of application and the numerous advantages of CTAs, their use in regulatory toxicology has been limited in part due to concerns about the subjective nature of visual scoring, i...
December 5, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27912163/reproduction-impairment-and-endocrine-disruption-in-adult-zebrafish-danio-rerio-after-waterborne-exposure-to-tboep
#2
Qinglong Xu, Ding Wu, Yao Dang, Liqin Yu, Chunsheng Liu, Jianghua Wang
Tris (2-butoxyethyl) phosphate (TBOEP) is widely used as a substitute of polybrominated diphenyl ethers (PBDEs). It has been frequently measured at concentrations of micrograms per liter (μg/L) in surface waters and waste water. However, limited information is available about the reproduction toxicology of TBOEP. In this study, adult zebrafish pairs were exposed to TBOEP at concentrations of 0, 5, 50, and 500μg/L for 21days. The effects on reproduction, hormone concentration, transcription of genes along the hypothalamic-pituitary-gonadal (HPG) axis, and gonadal development were investigated...
November 24, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27905399/cellular-reactions-to-long-term-volatile-organic-compound-voc-exposures
#3
Johanna M Gostner, Johannes Zeisler, Mohammad Tauqeer Alam, Peter Gruber, Dietmar Fuchs, Kathrin Becker, Kerstin Neubert, Markus Kleinhappl, Stefan Martini, Florian Überall
Investigations of cellular processes initiated by volatile organic compounds (VOCs) are limited when modelling realistic long-term exposure scenarios at low concentrations. Exposure to indoor VOCs is associated with a range of adverse effects, but data on molecular changes at regulatory threshold limits are lacking. Activity analysis of VOC in vitro can be a valuable complement to inhalation toxicological evaluations. We developed an exposure platform that generates a stable VOC atmosphere and allows the exposure of cells for longer periods...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27886581/a-multi-omic-approach-to-elucidate-low-dose-effects-of-xenobiotics-in-zebrafish-danio-rerio-larvae
#4
Susie S Y Huang, Jonathan P Benskin, Nik Veldhoen, Bharat Chandramouli, Heather Butler, Caren C Helbing, John R Cosgrove
Regulatory-approved toxicity assays such as the OECD Fish Embryo Toxicity Assay (TG236) allow correlation of chemical exposure to adverse morphological phenotypes. However, these assays are ineffective in assessing sub-lethal (i.e. low-dose) effects, or differentiating between similar phenotypes induced by different chemicals. Inclusion of multi-omic analyses in studies investigating xenobiotic action provides improved characterization of biological response, thereby enhancing prediction of toxicological outcomes in whole animals in the absence of morphological effects...
November 18, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27883231/evaluating-the-credibility-of-histopathology-data-in-environmental-endocrine-toxicity-studies
#5
REVIEW
Jeffrey C Wolf, Gerd Maack
Agencies responsible for environmental protection are tasked with developing regulatory guidance that is based on the best available scientific evidence. Histopathology is a common endpoint in toxicologic bioassays; however, because of the subjective nature of this endpoint, and the advanced level of specialized training required for its effective utilization, the reliability of histopathology data can be inconsistent. Consequently, mechanisms for evaluating such data on a case-by-case basis are needed. The purposes of this review are to describe a methodology that can be used to evaluate the credibility of histopathology findings, and discuss the results of such assessments as applied to real-world data collected from the scientific literature...
November 24, 2016: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/27864543/long-non-coding-rnas-a-novel-paradigm-for-toxicology
#6
REVIEW
Joseph L Dempsey, Julia Yue Cui
Long non-coding RNAs (lncRNAs) are over 200 nucleotides in length and are transcribed from the mammalian genome in a tissue-specific and developmentally regulated pattern. There is growing recognition that lncRNAs are novel biomarkers and/or key regulators of toxicological responses in humans and animal models. Lacking protein-coding capacity, the numerous types of lncRNAs possess a myriad of transcriptional regulatory functions that include cis and trans gene expression, transcription factor activity, chromatin remodeling, imprinting, and enhancer up-regulation...
November 17, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27858217/alternative-animal-and-non-animal-models-for-drug-discovery-and-development-bonus-or-burden
#7
Irlan Almeida Freires, Janaina de Cássia Orlandi Sardi, Ricardo Dias de Castro, Pedro Luiz Rosalen
Mammalian models have served as a basis for R&D over the past decades. Nevertheless, these models are expensive, laborious, may yield results that cannot always be translated into the human in vivo situation and, more recently, have reverberated great social and ethical dilemmas. Hence, the prospect of changes in the global scientific scenario and the Three Rs principle (Reduction, Replacement and Refinement) have encouraged the development of alternative methods to the use of mammals. Despite the efforts, suitable alternative tests are not available in all areas of biomedical research, as regulatory acceptance requires time, prior validation and robust financial and scientific investment...
November 17, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27847000/substance-exposure-and-helmet-use-in-all-terrain-vehicle-accidents-nine-years-of-experience-at-a-level-1-trauma-center
#8
Audis Bethea, Damayanti Samanta, John A Willis, Franck C Lucente, Julton Tomanguillo Chumbe
INTRODUCTION: The surging popularity of all-terrain vehicles (ATV) in the United States has caused an "epidemic of injuries and mortality." The U.S. Consumer Product Safety Commission reported 99,600 injuries and 426 fatalities from ATV accidents in 2013. The aim of this study was to examine the relationship between helmet use and positive toxicology screenings on outcomes in ATV accident victims. METHODS: This is a retrospective study of patients admitted to a Level 1 Trauma Center in southwestern West Virginia following an ATV accident between 2005 and 2013...
December 2016: Journal of Safety Research
https://www.readbyqxmd.com/read/27846345/systems-biology-for-organotypic-cell-cultures
#9
Sonia Grego, Edward R Dougherty, Francis J Alexander, Scott S Auerbach, Brian R Berridge, Michael L Bittner, Warren Casey, Philip C Cooley, Ajit Dash, Stephen S Ferguson, Timothy R Fennell, Brian T Hawkins, Anthony J Hickey, Andre Kleensang, Michael N J Liebman, Florian Martin, Elizabeth A Maull, Jason Paragas, Guilin Gary Qiao, Sreenivasa Ramaiahgari, Susan J Sumner, Miyoung Yoon
Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, "organotypic" cell cultures, which mimic functional responses of living tissue...
November 14, 2016: ALTEX
https://www.readbyqxmd.com/read/27844421/environmental-impacts-of-tobacco-product-waste-international-and-australian-policy-responses
#10
REVIEW
Lucinda A Wallbank, Ross MacKenzie, Paul J Beggs
The health risks of tobacco consumption are well established, but there is less awareness of the global environmental impacts of smoking. The by-products of the 6.3 trillion cigarettes smoked annually are filters (butts) that contain benzene, nicotine, cadmium, and dozens of other chemicals. It is estimated that between one- and two-thirds of all filters are discarded on roads, pavements, and green spaces. Butt litter as an environmental and public health hazard is a relatively new field of study, but recent research and findings have clear global implications...
November 14, 2016: Ambio
https://www.readbyqxmd.com/read/27821595/cannabis-exposure-as-an-interactive-cardiovascular-risk-factor-and-accelerant-of-organismal-ageing-a-longitudinal-study
#11
Albert Stuart Reece, Amanda Norman, Gary Kenneth Hulse
OBJECTIVES: Many reports exist of the cardiovascular toxicity of smoked cannabis but none of arterial stiffness measures or vascular age (VA). In view of its diverse toxicology, the possibility that cannabis-exposed patients may be ageing more quickly requires investigation. DESIGN: Cross-sectional and longitudinal, observational. Prospective. SETTING: Single primary care addiction clinic in Brisbane, Australia. PARTICIPANTS: 11 cannabis-only smokers, 504 tobacco-only smokers, 114 tobacco and cannabis smokers and 534 non-smokers...
November 7, 2016: BMJ Open
https://www.readbyqxmd.com/read/27814026/gper-gpr30-a-nongenomic-receptor-gpcr-for-steroid-hormones-with-implications-for-cardiovascular-disease-and-cancer
#12
Ross D Feldman, Lee E Limbird
Although the rapid effects of steroids, such as estrogen and aldosterone, were postulated originally to be nongenomic, it is now appreciated that activation of such signaling pathways via a steroid-acting G protein-coupled receptor, the G protein estrogen receptor (GPER), has important transcription-dependent outcomes in the regulation of cell growth and programmed cell death secondary to GPER-regulated second-messenger pathways. GPER is expressed ubiquitously and has diverse biological effects, including regulation of endocrine, immune, neuronal, and cardiovascular functions...
October 21, 2016: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27809675/bentonite-toxicology-and-epidemiology-a-review
#13
L Daniel Maxim, Ron Niebo, Ernest E McConnell
Bentonite, a clay with numerous industrial and consumer applications, is mined and processed in many countries of the world. Its many beneficial uses also create the potential for widespread occupational and consumer exposure. The available studies on toxicity and epidemiology indicate that the principal exposure pathway of concern is inhalation of respirable dust by occupationally exposed cohorts. Bentonite itself is probably not more toxic than any other particulate not otherwise regulated and is not classified as a carcinogen by any regulatory or advisory body, but some bentonite may contain variable amounts of respirable crystalline silica, a recognized human carcinogen...
November 2016: Inhalation Toxicology
https://www.readbyqxmd.com/read/27805827/nrf2-activation-as-a-key-event-triggered-by-skin-sensitisers-the-development-of-the-stable-keratinosens-reporter-gene-assay
#14
REVIEW
Andreas Natsch, Roger Emter
The 21st century paradigm for toxicology and the adverse outcome pathway concept envisage a future toxicology largely based on mechanistic in vitro assays and relying mainly on cellular models. In the skin sensitisation field, this concept was not intuitive at the beginning. Given the high structural diversity of skin sensitising molecules, classical receptor binding as the molecular initiating event in a cell-based assay could be excluded from the start, leaving the question of how cells could sense potential skin sensitising chemicals and be able to differentiate them from non-sensitisers...
October 2016: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/27805823/it-takes-a-village-stakeholder-participation-is-essential-to-transforming-science
#15
REVIEW
Kristie Sullivan
Efforts toward replacing the use of animals in toxicology testing have begun to make significant headway in the last several years, due to co-operative and pragmatic efforts on the part of many stakeholders, and the public pressure that non-governmental advocacy organisations represent. Science-focused advocacy organisations have a unique role to play in these efforts, as they often have flexibility to adapt quickly to keep a project going and forge connections among different kinds of stakeholders to help encourage buy-in...
October 2016: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/27783963/new-insights-into-cytotoxicity-induced-by-microcystin-lr-estradiol-and-ractopamine-with-mathematical-models-individual-and-combined-effects
#16
Min Ma, Fuwei Pi, Jiasheng Wang, Jian Ji, Xiulan Sun
Humans are most likely to be exposed to microcystins (MCs) combined with other water pollutants rather than to individual compounds through the consumption of contaminated drinking water or through recreational activities, such as swimming. However, the combined effects of MC-LR, estradiol (EST), and ractopamine (RAC) have not been extensively researched. The goal of this study was to investigate the combined effects of these compounds. For this purpose, cytotoxicity was evaluated in HepG2 cells treated with single or combined doses of MC-LR, EST, and RAC based on concentration addition (CA), independent action (IA), and Chou-Talalay's combination-index (CI) methods...
October 23, 2016: Chemosphere
https://www.readbyqxmd.com/read/27780885/futuretox-iii-bridges-for-translation
#17
Daland R Juberg, Thomas B Knudsen, Miriam Sander, Nancy B Beck, Elaine M Faustman, Donna L Mendrick, John R Fowle, Thomas Hartung, Raymond R Tice, Emmanuel Lemazurier, Richard A Becker, Suzanne Compton Fitzpatrick, George P Daston, Alison Harrill, Ronald N Hines, Douglas A Keller, John C Lipscomb, David Watson, Tina Bahadori, Kevin M Crofton
Future Tox III, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in November 2015. Building upon Future Tox I and II, Future Tox III was focused on developing the high throughput risk assessment paradigm and taking the science of in vitro data and in silico models forward to explore the question-what progress is being made to address challenges in implementing the emerging big-data toolbox for risk assessment and regulatory decision-making. This article reports on the outcome of the workshop including 2 examples of where advancements in predictive toxicology approaches are being applied within Federal agencies, where opportunities remain within the exposome and AOP domains, and how collectively the toxicology community across multiple sectors can continue to bridge the translation from historical approaches to Tox21 implementation relative to risk assessment and regulatory decision-making...
October 25, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27775829/approved-and-experimental-small-molecule-oncology-kinase-inhibitor-drugs-a-mid-2016-overview
#18
Peter M Fischer
Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small-molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs have received regulatory approval for the treatment of a variety of cancers and the volume of reports on the discovery and development of kinase inhibitors has increased to an extent where it is now difficult-even for those working in the field-easily to keep an overview of the compounds that are being developed, as currently there are 231 such compounds, targeting 38 different protein and lipid kinases (not counting isoforms), in clinical use or under clinical investigation...
October 24, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27775817/stem-cell-derived-models-to-improve-mechanistic-understanding-and-prediction-of-human-drug-induced-liver-injury
#19
REVIEW
Christopher Goldring, Daniel J Antoine, Frank Bonner, Jonathan Crozier, Chris Denning, Robert J Fontana, Neil A Hanley, David C Hay, Magnus Ingelman-Sundberg, Satu Juhila, Neil Kitteringham, Beatriz Silva-Lima, Alan Norris, Chris Pridgeon, James A Ross, Rowena Sison Young, Danilo Tagle, Belen Tornesi, Bob van de Water, Richard J Weaver, Fang Zhang, B Kevin Park
Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalized toxicology to determine interindividual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury means that no current single-cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human drug-induced liver injury...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27770640/potential-of-the-small-cyclopoid-copepod-paracyclopina-nana-as-an-invertebrate-model-for-ecotoxicity-testing
#20
Hans-Uwe Dahms, Eun-Ji Won, Hui-Su Kim, Jeonghoon Han, Heum Gi Park, Sami Souissi, Sheikh Raisuddin, Jae-Seong Lee
Aquatic invertebrates contribute significantly to environmental impact assessment of contaminants in aquatic ecosystems. Much effort has been made to identify viable and ecologically relevant invertebrate test organisms to meet rigorous regulatory requirements. Copepods, which are ecologically important and widely distributed in aquatic organisms, offer a huge opportunity as test organisms for aquatic toxicity testing. They have a major role not only in the transfer of energy in aquatic food chains, but also as a medium of transfer of aquatic pollutants across the tropic levels...
October 14, 2016: Aquatic Toxicology
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