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Predictive toxicology

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https://www.readbyqxmd.com/read/28647084/bioprinted-three-dimensional-human-tissues-for-toxicology-and-disease-modeling
#1
REVIEW
Deborah G Nguyen, Stephen L Pentoney
The high rate of attrition among clinical-stage therapies, due largely to an inability to predict human toxicity and/or efficacy, underscores the need for in vitro models that better recapitulate in vivo human biology. In much the same way that additive manufacturing has revolutionized the production of solid objects, three-dimensional (3D) bioprinting is enabling the automated production of more architecturally and functionally accurate in vitro tissue culture models. Here, we provide an overview of the most commonly used bioprinting approaches and how they are being used to generate complex in vitro tissues for use in toxicology and disease modeling research...
March 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/28646506/three-lessons-for-genetic-toxicology-from-baseball-analytics
#2
EDITORIAL
Stephen D Dertinger
In many respects the evolution of baseball statistics mirrors advances made in the field of genetic toxicology. From its inception, baseball and statistics have been inextricably linked. Generations of players and fans have used a number of relatively simple measurements to describe team and individual player's current performance, as well as for historical record-keeping purposes. Over the years, baseball analytics has progressed in several important ways. Early advances were based on deriving more meaningful metrics from simpler forerunners...
June 24, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28638154/-assessment-of-predictive-dermal-exposure-to-chemicals-in-the-work-environment
#3
Agnieszka Jankowska, Sławomir Czerczak, Małgorzata Kupczewska-Dobecka
Assessment of dermal exposure to chemicals in the work environment is problematic, mainly as a result of the lack of measurement data on occupational exposure to chemicals. Due to common prevalence of occupational skin exposure and its health consequences it is necessary to look for efficient solutions allowing for reliable exposure assessment. The aim of the study is to present predictive models used to assess non-measured dermal exposure, as well as to acquaint Polish users with the principles of the selected model functioning...
June 14, 2017: Medycyna Pracy
https://www.readbyqxmd.com/read/28637216/qualitative-analysis-and-detection-of-the-pyrolytic-products-of-jwh-018-and-11-additional-synthetic-cannabinoids-in-the-presence-of-common-herbal-smoking-substrates
#4
Stephen Raso, Suzanne Bell
Synthetic cannabinoids have become a ubiquitous challenge in forensic toxicology and seized drug analysis. Thermal degradation products have yet to be identified and evaluated for toxicity in comparison to parent and metabolic compounds. An investigation into these pyrolytic products, as the major route of ingestion is inhalation, may produce additional insight to understand the toxicity of synthetic cannabinoids. The pyrolysis of JWH-018 and 11 additional synthetic cannabinoids and six herbal plant substrates were conducted using an in-house constructed smoking simulator...
June 20, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28636099/spectators-or-participants-how-can-setac-become-more-engaged-in-international-climate-change-research-programs
#5
Ralph G Stahl, Jennifer L Stauber, William H Clements
Environmental toxicologists and chemists have been crucial to evaluating the chemical fate and toxicological effects of environmental contaminants, including chlorinated pesticides, before and after Rachel Carson's publication of Silent Spring in 1962. Like chlorinated pesticides previously, global climate change is widely considered to be one of the most important environmental challenges of our time. Over the past 30 yr, climate scientists and modelers have shown that greenhouse gases such as CO2 and CH4 cause radiative forcing (climate forcing) and lead to increased global temperatures...
June 21, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28633424/three-dimensional-3d-heparg-spheroid-model-with-physiologically-relevant-xenobiotic-metabolism-competence-and-hepatocyte-functionality-for-liver-toxicity-screening
#6
Sreenivasa C Ramaiahgari, Suramya Waidyanatha, Darlene Dixon, Michael J DeVito, Richard S Paules, Stephen S Ferguson
Effective prediction of human responses to chemical and drug exposure is of critical importance in environmental toxicology research and drug development. While significant progress has been made to address this challenge using in vitro liver models, these approaches often fail due to inadequate tissue model functionality. Herein, we describe the development, optimization, and characterization of a novel three-dimensional (3D) spheroid model using differentiated HepaRG cells that achieve and maintain physiologically-relevant levels of xenobiotic metabolism (CYP1A2, CYP2B6, and CYP3A4/5)...
June 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28628818/in-vitro-assessment-of-the-toxicity-of-bushfire-emissions-a-review
#7
REVIEW
Trang T T Dong, Andrea L Hinwood, Anna C Callan, Graeme Zosky, William D Stock
Bushfires produce many toxic pollutants and the smoke has been shown to have negative effects on human health, especially to the respiratory system. Bushfires are predicted to increase in size and frequency, leading to a greater incidence of smoke and impacts. While there are many epidemiological studies of the potential impact on populations, there are few studies using in vitro methods to investigate the biological effects of bushfire emissions to better understand its toxicity and significance. This review focused on the literature pertaining to in vitro toxicity testing to determine the state of knowledge on current methods and findings on the impacts of bushfire smoke...
June 16, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28624430/comparative-assessment-of-immune-complex-mediated-hypersensitivity-reactions-with-biotherapeutics-in-the-non-human-primate-critical-parameters-safety-and-lessons-for-future-studies
#8
Sven Kronenberg, Elisabeth Husar, Christine Schubert, Christian Freichel, Thomas Emrich, Martin Lechmann, Anna Maria Giusti, Franziska Regenass
With the emergence of novel biotherapeutic formats and immunostimulatory biotherapeutics in cancer immunotherapy, an understanding of immune-complex (IC) mediated hypersensitivity reactions in toxicology studies - and their differentiation from pharmacology - remains key to the preclinical evaluation of these drugs. In this review we provide an in-depth evaluation and comparison of case examples where IC-mediated hypersensitivity reactions were observed in cynomolgus monkeys. We provide details of the parameters evaluated in each study to substantiate and guide the interpretation of these findings...
June 15, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28615142/overexpression-of-kcnj2-in-induced-pluripotent-stem-cell-derived-cardiomyocytes-for-the-assessment-of-qt-prolonging-drugs
#9
Min Li, Yasunari Kanda, Takashi Ashihara, Tetsuo Sasano, Yuji Nakai, Masami Kodama, Erina Hayashi, Yuko Sekino, Tetsushi Furukawa, Junko Kurokawa
Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes hold great potentials to predict pro-arrhythmic risks in preclinical cardiac safety screening, although the hiPSC cardiomyocytes exhibit rather immature functional and structural characteristics, including spontaneous activity. Our physiological characterization and mathematical simulation showed that low expression of the inward-rectifier potassium (IK1) channel is a determinant of spontaneous activity. To understand impact of the low IK1 expression on the pharmacological properties, we tested if transduction of hiPSC-derived cardiomyocytes with KCNJ2, which encodes the IK1 channel, alters pharmacological response to cardiac repolarization processes...
May 27, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28606765/genotoxicity-assessment-of-piperitenone-oxide-an-in%C3%A2-vitro-and-in-silico-evaluation
#10
Antonella Di Sotto, Silvia Di Giacomo, Lorena Abete, Mijat Božović, Olga A Parisi, Fabio Barile, Annabella Vitalone, Angelo A Izzo, Rino Ragno, Gabriela Mazzanti
Piperitenone oxide, a natural flavouring agent also known as rotundifolone, has been studied for the genotoxicity assessment by an integrated in vitro and in silico experimental approach, including the bacterial reverse mutation assay, the micronucleus test, the comet assay and the computational prediction by Toxtree and VEGA tools. Under our experimental conditions, the monoterpene showed to induce both point mutations (i.e. frameshift, base-substitution and/or oxidative damage) and DNA damage (i.e. clastogenic or aneuploidic damage, or single-strand breaks)...
June 10, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28601767/pooled-human-liver-preparations-heparg-or-hepg2-cell-lines-for-metabolism-studies-of-new-psychoactive-substances-a-study-using-mdma-mdbd-butylone-mdppp-mdpv-mdpb-5-mapb-and-5-api-as-examples
#11
Lilian H J Richter, Veit Flockerzi, Hans H Maurer, Markus R Meyer
Metabolism studies play an important role in clinical and forensic toxicology. Because of potential species differences in metabolism, human samples are best suitable for elucidating metabolism. However, in the case of new psychoactive substances (NPS), human samples of controlled studies are not available. Primary human hepatocytes have been described as gold standard for in vitro metabolism studies, but there are some disadvantages such as high costs, limited availability, and variability of metabolic enzymes...
May 18, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28595837/application-of-caenorhabditis-elegans-nematode-and-danio-rerio-embryo-zebrafish-as-model-systems-to-screen-for-developmental-and-reproductive-toxicity-of-piperazine-compounds
#12
Peter I Racz, Marjolein Wildwater, Martijn Rooseboom, Engelien Kerkhof, Raymond Pieters, Elena Santidrian Yebra-Pimentel, Ron P Dirks, Herman P Spaink, Chantal Smulders, Graham F Whale
To enable selection of novel chemicals for new processes, there is a recognized need for alternative toxicity screening assays to assess potential risks to man and the environment. For human health hazard assessment these screening assays need to be translational to humans, have high throughput capability, and from an animal welfare perspective be harmonized with the principles of the 3Rs (Reduction, Refinement, Replacement). In the area of toxicology a number of cell culture systems are available but while these have some predictive value, they are not ideally suited for the prediction of developmental and reproductive toxicology (DART)...
June 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28586416/bridging-the-gap-between-reproducibility-and-translation-data-resources-and-approaches
#13
Caroline J Zeiss, Linda K Johnson
Animal research has constituted a fundamental means to achieve groundbreaking therapies for human disease. However, for complex diseases, promising preclinical results have failed to translate to the clinic. Reasons for this disparity are multifactorial. These include the challenges inherent in modeling complex disease in animals, as well issues of study design, reproducibility and operational norms within the biomedical research enterprise. In this issue, we explore the range of information resources available for the comparative study of disease, as well as challenges to the ultimate translation of preclinical findings...
June 6, 2017: ILAR Journal
https://www.readbyqxmd.com/read/28583787/coatings-in-food-contact-materials-potential-source-of-genotoxic-contaminants
#14
Birgit Mertens, M Van Bossuyt, S Fraselle, M N Blaude, T Vanhaecke, V Rogiers, L Verschaeve, E Van Hoeck
Up till now, no harmonized EU regulation exists on chemicals used in coatings for food contact materials (FCM). Therefore, these substances need to comply with the general provisions of EU Regulation 1935/2004 and, if present, with national legislation. Different 'inventory lists' of compounds that might be present in coatings are available, but for hundreds of these substances, the potential human health impact of their use in FCM coatings has not (recently) been evaluated. Since detailed evaluation of all compounds is not feasible, a pragmatic approach was developed to identify substances with a potential concern for human health...
June 3, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28562095/the-advancement-of-multidimensional-qsar-for-novel-drug-discovery-where-are-we-headed
#15
Tao Wang, Xin-Song Yuan, Mian-Bin Wu, Jian-Ping Lin, Li-Rong Yang
The Multidimensional quantitative structure-activity relationship (multidimensional-QSAR) method is one of the most popular computational methods employed to predict interesting biochemical properties of existing or hypothetical molecules. With continuous progress, the QSAR method has made remarkable success in various fields, such as medicinal chemistry, material science and predictive toxicology. Areas covered: In this review, the authors cover the basic elements of multidimensional -QSAR including model construction, validation and application...
June 8, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28558277/cytotoxicity-and-genotoxicity-of-anticancer-drug-residues-and-their-mixtures-in-experimental-model-with-zebrafish-liver-cells
#16
Matjaž Novak, Bojana Žegura, Barbara Modic, Ester Heath, Metka Filipič
Anticancer drugs enter aquatic environment predominantly via hospital and municipal wastewater effluents where they may, due to their genotoxic potential, cause adverse environmental effects even at very low doses. In this study we evaluated cytotoxic and genotoxic potential of two widely used anticancer drugs, cyclophosphamide (CP) and ifosfamide (IF) as individual compounds and in a complex mixture together with 5-fluorouracil (5-FU) and cisplatin (CDDP) because these four drugs have been frequently detected in an oncological ward effluents...
May 27, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28557712/an-integrated-chemical-environment-to-support-21st-century-toxicology
#17
Shannon M Bell, Jason Phillips, Alexander Sedykh, Arpit Tandon, Catherine Sprankle, Stephen Q Morefield, Andy Shapiro, David Allen, Ruchir Shah, Elizabeth A Maull, Warren M Casey, Nicole C Kleinstreuer
Access to high-quality reference data is essential for the development, validation, and implementation of in vitro and in silico approaches that reduce and replace the use of animals in toxicity testing. Currently, these data must often be pooled from a variety of disparate sources to efficiently link a set of assay responses and model predictions to an outcome or hazard classification. To provide a central access point for these purposes, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods developed the Integrated Chemical Environment (ICE) web resource...
May 24, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28552772/pcb-28-metabolites-elimination-kinetics-in-human-plasma-on-a-real-case-scenario-study-of-hydroxylated-polychlorinated-biphenyl-oh-pcb-metabolites-of-pcb-28-in-a-highly-exposed-german-cohort
#18
Natalia Quinete, André Esser, Thomas Kraus, Thomas Schettgen
Polychlorinated biphenyls (PCBs) are suspected of carcinogenic, neurotoxic and immunotoxic effects in animals and humans. Although background levels of PCBs have been slowly decreased after their ban, they are still among the most persistent and ubiquitous pollutants in the environment, remaining the subject of great concern. PCB 28 is a trichlorinated PCB found in high concentrations not only in human plasma but also in indoor air in Europe, yet little is known about its metabolic pathway and potential metabolites in humans...
July 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28551075/diagnostic-accuracy-of-post-mortem-ct-with-targeted-coronary-angiography-versus-autopsy-for-coroner-requested-post-mortem-investigations-a-prospective-masked-comparison-study
#19
Guy N Rutty, Bruno Morgan, Claire Robinson, Vimal Raj, Mini Pakkal, Jasmin Amoroso, Theresa Visser, Sarah Saunders, Mike Biggs, Frances Hollingbury, Angus McGregor, Kevin West, Cathy Richards, Laurence Brown, Rebecca Harrison, Roger Hew
BACKGROUND: England and Wales have one of the highest frequencies of autopsy in the world. Implementation of post-mortem CT (PMCT), enhanced with targeted coronary angiography (PMCTA), in adults to avoid invasive autopsy would have cultural, religious, and potential economic benefits. We aimed to assess the diagnostic accuracy of PMCTA as a first-line technique in post-mortem investigations. METHODS: In this single-centre (Leicester, UK), prospective, controlled study, we selected cases of natural and non-suspicious unnatural death referred to Her Majesty's (HM) Coroners...
May 24, 2017: Lancet
https://www.readbyqxmd.com/read/28540764/japan-flavour-and-fragrance-materials-association-s-safety-assessment-of-food-flavouring-substances-uniquely-used-in-japan-that-belong-to-the-class-of-aliphatic-primary-alcohols-aldehydes-carboxylic-acids-acetals-and-esters-containing-additional-oxygenated
#20
Kenji Saito, Yasuko Hasegawa-Baba, Fumiko Sekiya, Shim-Mo Hayashi, Yoshiharu Mirokuji, Hiroyuki Okamura, Shinpei Maruyama, Atsushi Ono, Madoka Nakajima, Masakuni Degawa, Shogo Ozawa, Makoto Shibutani, Tamio Maitani
We performed a safety evaluation using the procedure devised by the Joint FAO/WHO Expert Committee on Food Additives of the following four flavouring substances that belong to the class of 'aliphatic primary alcohols, aldehydes, carboxylic acids, acetals, and esters containing additional oxygenated functional groups' and are uniquely used in Japan: butyl butyrylacetate, ethyl 2-hydroxy-4-methylpentanoate, 3-hydroxyhexanoic acid and methyl hydroxyacetate. Although no genotoxicity study data were found in the published literature, none of the four substances had chemical structural alerts predicting genotoxicity...
May 25, 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
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