keyword
MENU ▼
Read by QxMD icon Read
search

Predictive toxicology

keyword
https://www.readbyqxmd.com/read/27923611/cumulative-effects-of-antiandrogenic-chemical-mixtures-and-their-relevance-to-human-health-risk-assessment
#1
REVIEW
Kembra L Howdeshell, Andrew K Hotchkiss, L Earl Gray
Toxicological studies of defined chemical mixtures assist human health risk assessment by establishing how chemicals interact with one another to induce an effect. This paper reviews how antiandrogenic chemical mixtures can alter reproductive tract development in rats with a focus on the reproductive toxicant phthalates. The reviewed studies compare observed mixture data to mathematical mixture model predictions based on dose addition or response addition to determine how the individual chemicals in a mixture interact (e...
November 19, 2016: International Journal of Hygiene and Environmental Health
https://www.readbyqxmd.com/read/27920722/a-new-structure-activity-relationship-sar-model-for-predicting-drug-induced-liver-injury-based-on-statistical-and-expert-based-structural-alerts
#2
Fabiola Pizzo, Anna Lombardo, Alberto Manganaro, Emilio Benfenati
The prompt identification of chemical molecules with potential effects on liver may help in drug discovery and in raising the levels of protection for human health. Besides in vitro approaches, computational methods in toxicology are drawing attention. We built a structure-activity relationship (SAR) model for evaluating hepatotoxicity. After compiling a data set of 950 compounds using data from the literature, we randomly split it into training (80%) and test sets (20%). We also compiled an external validation set (101 compounds) for evaluating the performance of the model...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27916216/endocarditis-as-a-marker-for-new-epidemics-of-injection-drug-use
#3
Susana Williams Keeshin, Judith Feinberg
BACKGROUND: We examined discharges for infective endocarditis (IE) at an academic teaching hospital for over 10 years to evaluate if an increase in hospitalizations for IE and increase in hepatitis C virus (HCV) in patients with IE could predict a new epidemic of injection drug use (IDU). MATERIALS AND METHODS: Retrospective medical record review of discharged patients with the diagnosis of IE as defined by the modified Duke criteria. Student's t test, chi-squared test and Fisher's exact test were used to calculate P values...
December 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27909741/the-role-of-epigenetic-modifiers-in-extended-cultures-of-functional-hepatocyte-like-cells-derived-from-human-neonatal-mesenchymal-stem-cells
#4
M Cipriano, J C Correia, S P Camões, N G Oliveira, P Cruz, H Cruz, M Castro, J L Ruas, J M Santos, J P Miranda
The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO)...
December 1, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27903868/allee-effect-in-polar-bears-a-potential-consequence-of-polychlorinated-biphenyl-contamination
#5
Viola Pavlova, Jacob Nabe-Nielsen, Rune Dietz, Christian Sonne, Volker Grimm
Polar bears (Ursus maritimus) from East Greenland and Svalbard exhibited very high concentrations of polychlorinated biphenyls (PCBs) in the 1980s and 1990s. In Svalbard, slow population growth during that period was suspected to be linked to PCB contamination. In this case study, we explored how PCBs could have impacted polar bear population growth and/or male reproductive success in Svalbard during the mid-1990s by reducing the fertility of contaminated males. A dose-response relationship linking the effects of PCBs to male polar bear fertility was extrapolated from studies of the effects of PCBs on sperm quality in rodents...
November 30, 2016: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/27894055/indirect-effects-of-climate-changes-on-cadmium-bioavailability-and-biological-effects-in-the-mediterranean-mussel-mytilus-galloprovincialis
#6
Alessandro Nardi, Luana Fiorella Mincarelli, Maura Benedetti, Daniele Fattorini, Giuseppe d'Errico, Francesco Regoli
Despite the great interest in the consequences of climate change on the physiological functioning of marine organisms, indirect and interactive effects of rising temperature and pCO2 on bioaccumulation and responsiveness to environmental pollutants are still poorly explored, particularly in terms of cellular mechanisms. According to future projections of temperature and pH/pCO2, this study investigated the main cellular pathways involved in metal detoxification and oxidative homeostasis in Mediterranean mussels, Mytilus galloprovincialis, exposed for 4 weeks to various combinations of two levels of pH/pCO2 (8...
November 25, 2016: Chemosphere
https://www.readbyqxmd.com/read/27890808/use-of-physiologically-based-kinetic-modeling-facilitated-reverse-dosimetry-of-in-vitro-toxicity-data-for-prediction-of-in-vivo-developmental-toxicity-of-tebuconazole-in-rats
#7
Hequn Li, Mengying Zhang, Jacques Vervoort, Ivonne M C M Rietjens, Bennard van Ravenzwaay, Jochem Louisse
Toxicological hazard and risk assessment largely rely on animal testing. For economic and ethical reasons, the development and validation of reliable alternative methods for these animal studies, such as in vitro assays, are urgently needed. In vitro concentration-response curves, however, need to be translated into in vivo dose-response curves for risk assessment purposes. In the present study, we translated in vitro concentration-response data of the antifungal compound tebuconazole, obtained in the ES-D3 cell differentiation assay, into predicted in vivo dose-response data for developmental toxicity using physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry...
November 24, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27888373/combined-toxic-effect-of-airborne-heavy-metals-on-human-lung-cell-line-a549
#8
Yeowool Choi, Kihong Park, Injeong Kim, Sang D Kim
Many studies have demonstrated that heavy metals existing as a mixture in the atmospheric environment cause adverse effects on human health and are important key factors of cytotoxicity; however, little investigation has been conducted on a toxicological study of a metal mixture from atmospheric fine particulate matter. The objective of this study was to predict the combined effects of heavy metals in aerosol by using in vitro human cells and obtain a suitable mixture toxicity model. Arsenic, nickel, and lead were selected for mixtures exposed to A549 human lung cancer cells...
November 25, 2016: Environmental Geochemistry and Health
https://www.readbyqxmd.com/read/27886581/a-multi-omic-approach-to-elucidate-low-dose-effects-of-xenobiotics-in-zebrafish-danio-rerio-larvae
#9
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/27885692/physiologically-based-pharmacokinetic-model-for-ethyl-tertiary-butyl-ether-and-tertiary-butyl-alcohol-in-rats-contribution-of-binding-to-%C3%AE-2u-globulin-in-male-rats-and-high-exposure-nonlinear-kinetics-to-toxicity-and-cancer-outcomes
#10
Susan J Borghoff, Caroline Ring, Marcy I Banton, Teresa L Leavens
In cancer bioassays, inhalation, but not drinking water exposure to ethyl tertiary-butyl ether (ETBE), caused liver tumors in male rats, while tertiary-butyl alcohol (TBA), an ETBE metabolite, caused kidney tumors in male rats following exposure via drinking water. To understand the contribution of ETBE and TBA kinetics under varying exposure scenarios to these tumor responses, a physiologically based pharmacokinetic model was developed based on a previously published model for methyl tertiary-butyl ether, a structurally similar chemical, and verified against the literature and study report data...
November 24, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27884470/the-first-exposure-assessment-of-legacy-and-unrestricted-brominated-flame-retardants-in-predatory-birds-of-pakistan
#11
Naeem Akhtar Abbasi, Igor Eulaers, Veerle Leontina Bernard Jaspers, Muhammad Jamshed Iqbal Chaudhry, Adrien Frantz, Per Lennart Ambus, Adrian Covaci, Riffat Naseem Malik
The exposure to legacy polybrominated diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDDs) and unrestricted 1,2-bis (2,4,6-tribromophenoxy) ethane (BTBPE), bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP) and 2-ethylhexyl-2,3,4,5-tetrabromo-benzoate (EH-TBB) was examined in tail feathers of 76 birds belonging to ten predatory species inhabiting Pakistan. In addition, different feather types of six individuals of Black kite (Milvus migrans) were compared for their brominated flame retardant (BFR) levels...
January 2017: Environmental Pollution
https://www.readbyqxmd.com/read/27874325/mixed-beam-murine-harderian-gland-tumorigenesis-predicted-dose-effect-relationships-if-neither-synergism-nor-antagonism-occurs
#12
Nopphon Siranart, Eleanor A Blakely, Alden Cheng, Naval Handa, Rainer K Sachs
Complex mixed radiation fields exist in interplanetary space, and little is known about their late effects on space travelers. In silico synergy analysis default predictions are useful when planning relevant mixed-ion-beam experiments and interpreting their results. These predictions are based on individual dose-effect relationships (IDER) for each component of the mixed-ion beam, assuming no synergy or antagonism. For example, a default hypothesis of simple effect additivity has often been used throughout the study of biology...
November 22, 2016: Radiation Research
https://www.readbyqxmd.com/read/27871868/quantitative-risk-assessment-for-skin-sensitization-success-or-failure
#13
Ian Kimber, G Frank Gerberick, David A Basketter
Skin sensitization is unique in the world of toxicology. There is a combination of reliable, validated predictive test methods for identification of skin sensitizing chemicals, a clearly documented and transparent approach to risk assessment, and effective feedback from dermatology clinics around the world delivering evidence of the success or failure of the hazard identification/risk assessment/management process. Recent epidemics of contact allergy, particularly to preservatives, have raised questions of whether the safety/risk assessment process is working in an optimal manner (or indeed is working at all!)...
November 18, 2016: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/27867423/marginalized-zero-altered-models-for-longitudinal-count-data
#14
Loni Philip Tabb, Eric J Tchetgen Tchetgen, Greg A Wellenius, Brent A Coull
Count data often exhibit more zeros than predicted by common count distributions like the Poisson or negative binomial. In recent years, there has been considerable interest in methods for analyzing zero-inflated count data in longitudinal or other correlated data settings. A common approach has been to extend zero-inflated Poisson models to include random effects that account for correlation among observations. However, these models have been shown to have a few drawbacks, including interpretability of regression coefficients and numerical instability of fitting algorithms even when the data arise from the assumed model...
October 2016: Statistics in Biosciences
https://www.readbyqxmd.com/read/27866008/organs-on-chips-research-and-commercial-perspectives
#15
REVIEW
Aarathi Balijepalli, Vaibhav Sivaramakrishan
Traditional preclinical drug testing methods utilize animal models to predict pharmacology and toxicology profiles. However, the data obtained from such methods cannot be directly extrapolated to humans and often do not provide a safe starting dose for first-in-human studies. To overcome these limitations, researchers have developed organs-on-chips - microfluidic devices that can mimic the cellular architecture and physiology more accurately than conventional methods. Because accurate organ-level interactions can be achieved with these devices, they have the potential to provide a realistic determination of a drug's pharmacokinetics, pharmacodynamics and toxicity profile...
November 16, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27862218/toxicity-of-individual-pharmaceuticals-and-their-mixtures-to-aliivibrio-fischeri-evidence-of-toxicological-interactions-in-binary-combinations
#16
Valeria Di Nica, Sara Villa, Antonio Finizio
The combined toxicities of binary mixtures of veterinary pharmaceuticals active compounds (PhACs) were examined using the bioluminescent bacterium Aliivibrio fischeri as a test organism (Microtox® test). Mixtures were prepared at an equitoxic ratio that corresponded to the IC10 of individual PhACs. In addition, we determined the toxicity of a multi-component mixture that contained all of the investigated PhACs mixed at the ratio corresponding to their individual values of Predicted No Effect Concentrations (PNEC)...
November 16, 2016: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/27859025/modeling-drug-induced-neuropathy-using-human-ipscs-for-predictive-toxicology
#17
Ryo Ohara, Keiko Imamura, Fukiko Morii, Naohiro Egawa, Kayoko Tsukita, Takako Enami, Ran Shibukawa, Toshiki Mizuno, Masanori Nakagawa, Haruhisa Inoue
Drugs under development can cause unpredicted toxicity in humans due to differential drug responsiveness between humans and other disease models, resulting in clinical trial failures. Human induced pluripotent stem cells (iPSCs) are expected to represent a useful tool for toxicity testing. However, among many assays, appropriate cellular assays for predicting neurotoxicity in an iPSC-based model are still uncertain. Here, we generated neurons from iPSCs of Charcot-Marie-Tooth disease (CMT) patients, who are sensitive to anti-cancer drugs and present with the adverse reaction of neuropathy, and analyzed cellular phenotypes...
November 9, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27846345/systems-biology-for-organotypic-cell-cultures
#18
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/27829332/in-vitro-metabolite-profiling-of-adb-fubinaca-a-new-synthetic-cannabinoid
#19
Jeremy Carlier, Xingxing Diao, Ariane Wohlfarth, Karl Scheidweiler, Marilyn A Huestis
Metabolite profiling of novel psychoactive substances (NPS) is critical for documenting drug consumption. N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA) is an emerging synthetic cannabinoid whose toxicological and metabolic data are currently unavailable. We aimed to determine optimal markers for identifying ADB-FUBINACA intake. Metabolic stability was evaluated with human liver microsome incubations. Metabolites were identified after 1 and 3 h incubation with pooled human hepatocytes, liquid chromatography- high resolution mass spectrometry in positive-ion mode (5600+ TripleTOF®, Sciex) and several data mining approaches (MetabolitePilot™, Sciex)...
November 8, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27818731/prediction-of-non-genotoxic-carcinogenicity-based-on-genetic-profiles-of-short-term-exposure-assays
#20
Luis Orlando Pérez, Rolando González-José, Pilar Peral García
Non-genotoxic carcinogens are substances that induce tumorigenesis by non-mutagenic mechanisms and long term rodent bioassays are required to identify them. Recent studies have shown that transcription profiling can be applied to develop early identifiers for long term phenotypes. In this study, we used rat liver expression profiles from the NTP (National Toxicology Program, Research Triangle Park, USA) DrugMatrix Database to construct a gene classifier that can distinguish between non-genotoxic carcinogens and other chemicals...
October 2016: Toxicological Research
keyword
keyword
3981
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"