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Predictive toxicology

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https://www.readbyqxmd.com/read/28936609/a-hierarchical-testing-strategy-for-micropollutants-in-drinking-water-regarding-their-potential-endocrine-disrupting-effects-towards-health-related-indicator-values
#1
Jochen Kuckelkorn, Regine Redelstein, Timon Heide, Jennifer Kunze, Sibylle Maletz, Petra Waldmann, Tamara Grummt, Thomas-Benjamin Seiler, Henner Hollert
In Germany, micropollutants that (may) occur in drinking water are assessed by means of the health-related indicator value (HRIV concept), developed by the German Federal Environment Agency. This concept offers five threshold values (≤ 0.01 to ≤ 3 μg l(-1)) depending on availability and completeness of data regarding genotoxicity, neurotoxicity, and germ cell-damaging potential. However, the HRIV concept is yet lacking integration of endocrine disruptors as one of the most prominent toxicological concerns in water bodies, including drinking water...
September 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28934728/has-toxicity-testing-moved-into-the-21st-century-a-survey-and-analysis-of-perceptions-in-the-field-of-toxicology
#2
Virginia Zaunbrecher, Elizabeth Beryt, Daniela Parodi, Donatello Telesca, Joseph Doherty, Timothy Malloy, Patrick Allard
BACKGROUND: Ten years ago, leaders in the field of toxicology called for a transformation of the discipline and a shift from primarily relying on traditional animal testing to incorporating advances in biotechnology and predictive methodologies into alternative testing strategies (ATS). Governmental agencies and academic and industry partners initiated programs to support such a transformation, but a decade later, the outcomes of these efforts are not well understood. OBJECTIVES: We aimed to assess the use of ATS and the perceived barriers and drivers to their adoption by toxicologists and by others working in, or closely linked with, the field of toxicology...
August 30, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28922667/integrated-strategy-for-mutagenicity-prediction-applied-to-food-contact-chemicals
#3
Serena Manganelli, Benoît Schilter, Emilio Benfenati, Alberto Manganaro, Elena Lo Piparo
Food contamination due to unintentional leakage of chemicals from food contact materials (FCM) is a source of increasing concern. Since for many of these substances, only limited or no toxicological data are available, the development of alternative methodologies to establish rapidly and cost-efficiently level of safety concern is critical to ensure adequate consumer protection. Computational toxicology methods are considered the most promising solutions to cope with this data gap. In particular, mutagenicity assessment has a particular relevance and is a mandatory requirement for all substances released from plastic FCM, regardless how low migration and exposure are...
September 18, 2017: ALTEX
https://www.readbyqxmd.com/read/28918194/cleaning-and-asthma-a-systematic-review-and-approach-for-effective-safety-assessment
#4
Melissa J Vincent, Ann Parker, Andrew Maier
Research indicates a correlative relationship between asthma and use of consumer cleaning products. We conduct a systematic review of epidemiological literature on persons who use or are exposed to cleaning products, both in occupational and domestic settings, and risk of asthma or asthma-like symptoms to improve understanding of the causal relationship between exposure and asthma. A scoring method for assessing study reliability is presented. Although research indicates an association between asthma and the use of cleaning products, no study robustly investigates exposure to cleaning products or ingredients along with asthma risk...
September 13, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28903775/nonclinical-and-clinical-pharmacology-evidence-for-cardiovascular-safety-of-saxagliptin
#5
REVIEW
Pia S Pollack, Kristina D Chadwick, David M Smith, Martin Billger, Boaz Hirshberg, Nayyar Iqbal, David W Boulton
BACKGROUND: In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial in patients with type 2 diabetes mellitus (T2D) at high risk of cardiovascular (CV) disease, saxagliptin did not increase the risk for major CV adverse events. However, there was an unexpected imbalance in events of hospitalization for heart failure (hHF), one of six components of the secondary CV composite endpoint, with a greater number of events observed with saxagliptin...
September 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28903496/editor-s-highlight-development-of-novel-neural-embryonic-stem-celltests-for-high-throughput-screening-of-embryotoxic-chemicals
#6
Kumiko Kobayashi, Noriyuki Suzuki, Kiyoshi Higashi, Akane Muroi, Florian Le Coz, Hirohisa Nagahori, Koichi Saito
There is a great demand for appropriate alternative methods to rapidly evaluate the developmental and reproductive toxicity of a wide variety of chemicals. We used the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes as a basis for establishing a rapid and highly reproducible invitro embryotoxicity test known as the Hand1-Luc Embryonic Stem Cell Test (Hand1-Luc EST). In this study, we developed novel neural-Luc ESTs using two marker genes for neural development, tubulin beta-3 (Tubb3) and Reelin (Reln), and evaluated the capacity of these tests to predict developmental toxicity...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903495/rna-seq-of-human-neural-progenitor-cells-exposed-to-lead-pb-reveals-transcriptome-dynamics-splicing-alterations-and-disease-risk-associations
#7
Peng Jiang, Zhonggang Hou, Jennifer M Bolin, James A Thomson, Ron Stewart
Lead (Pb) is a well-known toxicant, especially for the developing nervous system, albeit the mechanism is largely unknown. In this study, we use time series RNA-seq to conduct a genome-wide survey of the transcriptome response of human embryonic stem cell-derived neural progenitor cells to lead treatment. Using a dynamic time warping algorithm coupled with statistical tests, we find that lead can either accelerate or decelerate the expression of specific genes during the time series. We further show that lead disrupts a neuron- and brain-specific splicing factor NOVA1 regulated splicing network...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903485/editor-s-highlight-mechanistic-toxicity-tests-based-on-an-adverse-outcome-pathway-network-for-hepatic-steatosis
#8
Michelle M Angrish, Charlene A McQueen, Elaine Cohen-Hubal, Maribel Bruno, Yue Ge, Brian N Chorley
Risk assessors use liver endpoints in rodent toxicology studies to assess the safety of chemical exposures. Yet, rodent endpoints may not accurately reflect human responses. For this reason and others, human-based invitro models are being developed and anchored to adverse outcome pathways to better predict adverse human health outcomes. Here, a networked adverse outcome pathway-guided selection of biology-based assays for lipid uptake, lipid efflux, fatty acid oxidation, and lipid accumulation were developed...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28898253/engineering-human-cell-spheroids-to-model-embryonic-tissue-fusion-in-vitro
#9
David G Belair, Cynthia J Wolf, Carmen Wood, Hongzu Ren, Rachel Grindstaff, William Padgett, Adam Swank, Denise MacMillan, Anna Fisher, Witold Winnik, Barbara D Abbott
Epithelial-mesenchymal interactions drive embryonic fusion events during development, and perturbations of these interactions can result in birth defects. Cleft palate and neural tube defects can result from genetic defects or environmental exposures during development, yet very little is known about the effect of chemical exposures on fusion events during human development because of a lack of relevant and robust human in vitro assays of developmental fusion behavior. Given the etiology and prevalence of cleft palate and the relatively simple architecture and composition of the embryonic palate, we sought to develop a three-dimensional culture system that mimics the embryonic palate and could be used to study fusion behavior in vitro using human cells...
2017: PloS One
https://www.readbyqxmd.com/read/28894778/role-of-serum-creatinine-phosphokinase-in-outcome-prediction-of-intoxicated-patients-a-brief-report
#10
Bita Dadpour, Shahrad Tajoddini, Elham Shaarbaf Eidgahi, Mohsen Shokouhizadeh, Azam Shafahi
INTRODUCTION: Several mechanisms were introduced as causes of serum creatinine phosphokinase (CPK) raise in intoxicated patients. This study aimed to assess the relationship between serum CPK level in the first 24 hours and baseline characteristics as well as outcomes of these patients. METHODS: This one year retrospective cross-sectional study was conducted on all intoxicated patients, who were admitted to a referral toxicology center, Northwest of Iran, stayed for at least 24 hours and had serum CPK level more than 500 IU/L in the first 24 hours of admission...
2017: Emergency (Tehran, Iran)
https://www.readbyqxmd.com/read/28893587/current-nonclinical-testing-paradigm-enables-safe-entry-to-first-in-human-clinical-trials-the-iq-consortium-nonclinical-to-clinical-translational-database
#11
Thomas M Monticello, Thomas W Jones, Donna M Dambach, David M Potter, Michael W Bolt, Maggie Liu, Douglas A Keller, Timothy K Hart, Vivek J Kadambi
The contribution of animal testing in drug development has been widely debated and challenged. An industry-wide nonclinical to clinical translational database was created to determine how safety assessments in animal models translate to First-In-Human clinical risk. The blinded database was composed of 182 molecules and contained animal toxicology data coupled with clinical observations from phase I human studies. Animal and clinical data were categorized by organ system and correlations determined. The 2×2 contingency table (true positive, false positive, true negative, false negative) was used for statistical analysis...
September 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28886606/high-throughput-analysis-of-ovarian-cycle-disruption-by-mixtures-of-aromatase-inhibitors
#12
Frederic Y Bois, Nazanin Golbamaki-Bakhtyari, Simona Kovarich, Cleo Tebby, Henry A Gabb, Emmanuel Lemazurier
BACKGROUND: Combining computational toxicology with ExpoCast exposure estimates and ToxCast™ assay data gives us access to predictions of human health risks stemming from exposures to chemical mixtures. OBJECTIVES: We explored, through mathematical modeling and simulations, the size of potential effects of random mixtures of aromatase inhibitors on the dynamics of women's menstrual cycles. METHODS: We simulated random exposures to millions of potential mixtures of 86 aromatase inhibitors...
July 19, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28885075/compnanotox2015-novel-perspectives-from-a-european-conference-on-computational-nanotoxicology-on-predictive-nanotoxicology
#13
Miguel A Bañares, Andrea Haase, Lang Tran, Vladimir Lobaskin, Günter Oberdörster, Robert Rallo, Jerzy Leszczynski, Peter Hoet, Rafi Korenstein, Barry Hardy, Tomasz Puzyn
A first European Conference on Computational Nanotoxicology, CompNanoTox, was held in November 2015 in Benahavís, Spain with the objectives to disseminate and integrate results from the European modeling and database projects (NanoPUZZLES, ModENPTox, PreNanoTox, MembraneNanoPart, MODERN, eNanoMapper and EU COST TD1204 MODENA) as well as to create synergies within the European NanoSafety Cluster. This conference was supported by the COST Action TD1204 MODENA on developing computational methods for toxicological risk assessment of engineered nanoparticles and provided a unique opportunity for cross fertilization among complementary disciplines...
September 8, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28866265/chemical-induced-asthma-and-the-role-of-clinical-toxicological-exposure-and-epidemiological-research-in-regulatory-and-hazard-characterization-approaches
#14
Melissa J Vincent, Jonathan A Bernstein, David Basketter, Judy S LaKind, G Scott Dotson, Andrew Maier
Uncertainties in understanding all potential modes-of-action for asthma induction and elicitation hinders design of hazard characterization and risk assessment methods that adequately screen and protect against hazardous chemical exposures. To address this challenge and identify current research needs, the University of Cincinnati and the American Cleaning Institute hosted a webinar series to discuss the current state-of-science regarding chemical-induced asthma. The general consensus is that the available database, comprised of data collected from routine clinical and validated toxicological tests, is inadequate for predicting or determining causal relationships between exposures and asthma induction for most allergens...
September 1, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28853170/first-generation-annotations-for-the-fathead-minnow-pimephales-promelas-genome
#15
Travis W Saari, Anthony L Schroeder, Gerald T Ankley, Daniel L Villeneuve
Ab initio gene prediction and evidence alignment were used to produce the first annotations for the fathead minnow (Pimephales promelas) genome. We also describe a genome browser, hosted by the Society of Environmental Toxicology and Chemistry, that provides simplified access to the annotation data in context with the genomic sequence. The present study extends the utility of the fathead minnow genome and supports the continued development of this species as a model organism for predictive toxicology. Environ Toxicol Chem 2017;9999:1-7...
August 29, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28845507/toxicological-interactions-of-pesticide-mixtures-an-update
#16
REVIEW
Antonio F Hernández, Fernando Gil, Marina Lacasaña
Pesticides can interact with each other in various ways according to the compound itself and its chemical family, the dose and the targeted organs, leading to various effects. The term interaction means situations where some or all individual components of a mixture influence each other's toxicity and the joint effects may deviate from the additive predictions. The various mixture effects can be greatly determined by toxicokinetic and toxicodynamic factors involving metabolic pathways and cellular or molecular targets of individual pesticides, respectively...
August 28, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28844298/uv-vis-degradation-of-%C3%AE-tocopherol-in-a-model-system-and-in-a-cosmetic-emulsion-structural-elucidation-of-photoproducts-and-toxicological-consequences
#17
Ségolène De Vaugelade, Edith Nicol, Svetlana Vujovic, Sophie Bourcier, Stéphane Pirnay, Stéphane Bouchonnet
The UV-vis photodegradation of α-tocopherol was investigated in a model system and in a cosmetic emulsion. Both gas chromatography coupled with tandem mass spectrometry (GC-MS/MS) and high performance liquid chromatography coupled with ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (LC-UHR-MS) were used for photoproducts structural identification. Nine photoproduct families were detected and identified based on their mass spectra and additional experiments with α-tocopherol-d9; phototransformation mechanisms were postulated to rationalize their formation under irradiation...
August 8, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28842351/screening-of-pharmacokinetic-properties-of-fifty-dihydropyrimidin-thi-one-derivatives-using-a-combo-of-in-vitro-and-in-silico-assays
#18
Mariana Matias, Ana Fortuna, Joana Bicker, Samuel Silvestre, Amílcar Falcão, Gilberto Alves
The heterocycles dihydropyrimidin(thi)ones have been under intensive pharmacological research, but their pharmacokinetic properties remain almost unknown. Herein, fifty dihydropyrimidin(thi)ones were submitted to in vitro screening tests using parallel artificial membrane permeability assays (PAMPA) to evaluate their apparent permeability (Papp) through intestinal membrane and blood-brain barrier models, and cell-based assays to assess their interference on the efflux transporter P-glycoprotein (P-gp). Moreover, a set of kinetic and toxicological parameters was also estimated employing a new computational tool, the pkCSM...
August 24, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28837407/a-dynamic-energy-based-model-to-analyze-sublethal-effects-of-chronic-gamma-irradiation-in-the-nematode-caenorhabditis-elegans
#19
Catherine Lecomte-Pradines, Turid Hertel-Aas, Claire Coutris, Rodolphe Gilbin, Deborah Oughton, Frédéric Alonzo
Understanding how toxic contaminants affect wildlife species at various levels of biological organization (subcellular, histological, physiological, organism, and population levels) is a major research goal in both ecotoxicology and radioecology. A mechanistic understanding of the links between different observed perturbations is necessary to predict the consequences for survival, growth, and reproduction, which are critical for population dynamics. In this context, experimental and modeling studies were conducted using the nematode Caenorhabditis elegans...
August 24, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28830283/overview-on-biological-implications-of-metal-oxide-nanoparticle-exposure-to-human-alveolar-a549-cell-line
#20
Ansie Martin, Angshuman Sarkar
Metal oxides (MeOx) are exponentially being used in a wide range of applications and are the largest class of commercially produced nanomaterials. This presents unprecedented human exposure. Thus, understanding nanoparticle induced cellular stress can greatly help design strategies to combat them. Scores of studies have been carried out to understand the effects of MeOx nanoparticle exposure on human alveolar cells, which are highly susceptible to aerosolized matter. There is a huge redundancy of information generated, also, a lack of a comprehensive conglomeration of this information...
August 23, 2017: Nanotoxicology
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