Abstract：
INTRODUCTION:Computational methods have been widely applied to toxicology across pharmaceutical, consumer product and environmental fields over the past decade. Progress in computational toxicology is now reviewed. METHODS:A literature review was performed on computational models for hepatotoxicity (e.g. for drug-induced liver injury (DILI)), cardiotoxicity, renal toxicity and genotoxicity. In addition various publications have been highlighted that use machine learning methods. Several computational toxicology model datasets from past publications were used to compare Bayesian and Support Vector Machine (SVM) learning methods. RESULTS:The increasing amounts of data for defined toxicology endpoints have enabled machine learning models that have been increasingly used for predictions. It is shown that across many different models Bayesian and SVM perform similarly based on cross validation data. DISCUSSION:Considerable progress has been made in computational toxicology in a decade in both model development and availability of larger scale or 'big data' models. The future efforts in toxicology data generation will likely provide us with hundreds of thousands of compounds that are readily accessible for machine learning models. These models will cover relevant chemistry space for pharmaceutical, consumer product and environmental applications.
journal_name
J Pharmacol Toxicol Methodsjournal_title
Journal of pharmacological and toxicological methodsauthors
Ekins Sdoi
10.1016/j.vascn.2013.12.003subject
Has Abstractpub_date
2014-03-01 00:00:00pages
115-40issue
2eissn
1056-8719issn
1873-488Xpii
S1056-8719(13)00325-0journal_volume
69pub_type
杂志文章,评审abstract：INTRODUCTION:Although therapeutically beneficial in the treatment of certain diseases, L-type calcium channel antagonism can result in unwanted off-target pharmacology leading to adverse drug reactions and to the termination of the development of otherwise promising compounds. In the present study three marketed calciu...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2016.11.002
更新日期：2017-01-01 00:00:00
abstract：:Small interfering RNA (siRNA) directs the targeted destruction of mRNA encoding a specific protein, in a process known as RNA interference (RNAi). This stops translation of the targeted mRNA into protein, effectively silencing the gene. RNAi is a recent discovery, identified in mammalian cells in 2001, but it has rapi...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2004.08.012
更新日期：2005-05-01 00:00:00
abstract：:The potentiation of the antinociceptive effect of morphine by dipyrone (metamizol) and the possible participation of a peripheral mechanism on such synergism were studied with the use of the formalin test in the rat. Nociception was induced by the intraplantar injection of diluted formalin (1%) in the right hind paw. ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(00)00046-0
更新日期：1999-10-01 00:00:00
abstract：INTRODUCTION:The purpose of this study was to determine the sensitivity and specificity for predicting the liability of a compound to lengthen QTc using isolated, perfused guinea pig hearts (Langendorff preparation). METHODS:QTc (Fridericia correction) was calculated from bipolar transventricular electrograms. Hearts ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2003.08.003
更新日期：2004-01-01 00:00:00
abstract：INTRODUCTION:The aim of this experiment was to establish the usefulness of assessing temporal variability of the QT interval and changes in the T wave morphology in dogs as markers of pro-arrhythmic risk in humans. For this purpose, the electrocardiographic effects of astemizole and cisapride, two well known pro-arrhyt...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2008.03.001
更新日期：2008-05-01 00:00:00
abstract：:Chronic use of beta2-agonists and increased production of inflammatory mediators during the late allergic reaction after antigen challenge results in the desensitization of beta-adrenoceptors in the airways and the accompanying rise in nonspecific airway hyperresponsiveness. In this study, we established an in vivo mo...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(98)00046-x
更新日期：1998-08-01 00:00:00
abstract：:A model of gingival inflammation was performed in Sprague-Dawley rats weighing 180-200 g. Mechanical bamboo stick-induced injury was inflammatory when bacteria contaminated the sticks. Bacteria were first obtained from gingival fluid collected from a patient with adult periodontitis. Another strain from Institut Paste...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(94)90070-1
更新日期：1994-11-01 00:00:00
abstract：:A method for the rapid detection of intracellular nitric oxide (NO) generation in dissociated cerebellar granule cells using dichlorofluorescin (DCFH) and flow cytometry was developed. DCFH can be oxidized specifically by NO and this was assessed by 1) the use of SIN-1 (10 nM-100 microM), an NO donor, that induced a c...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(97)00066-x
更新日期：1997-10-01 00:00:00
abstract：INTRODUCTION:Parts A and B of the ICH S7 guidelines on safety pharmacology describe the in vivo studies that must be conducted prior to first time in man administration of any new pharmaceutical. ICH S7A requires a consideration of the sensitivity and reproducibility of the test systems used. This could encompass maint...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,多中心研究
doi：10.1016/j.vascn.2013.04.008
更新日期：2013-07-01 00:00:00
abstract：INTRODUCTION:The purpose of this study was to evaluate the feasibility of using gel electrophoresis combined with autoradiographic image analysis for quantitating protein drug concentrations in biological fluid for pharmacokinetic studies. METHODS:Protein drugs were iodinated using the Iodogen reagent and injected int...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(02)00203-4
更新日期：2002-01-01 00:00:00
abstract：:The application of microdialysis technique for the investigation of pharmacokinetics and pharmacodynamics of drugs requires careful assessment of probe performance to ensure validity of the data obtained using this technique. The aim of this study was to establish and validate the microdialysis technique for investiga...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(00)00117-9
更新日期：2000-11-01 00:00:00
abstract：INTRODUCTION:Ex vivo studies of human fetal hepatic drug metabolism are uncommon as it requires access to functional liver tissue and therefore raises practical and ethical concerns. Large animal models provide an alternative opportunity to study changes in cytochrome P450 (CYP) activity in the mother and fetus during ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2020.106934
更新日期：2020-01-01 00:00:00
abstract：INTRODUCTION:Recently we have demonstrated that to the choice of tissue type is important in identifying I(Kr) and I(Ks)-induced prolongation of the action potential. However, the differential sensitivity of cardiac tissues to other ionic current blockers or modulators is relatively unknown. The aim of the present stud...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2007.06.005
更新日期：2008-01-01 00:00:00
abstract：:There are three major assays that must be conducted in standard investigational new drug (IND) -enabling ototoxicity study designs: 1) functional acoustic threshold measurements (Auditory Brainstem Respsonse, ABR); 2) otohistopathology and 3) cytocochleograms. We provide evidence to demonstrate the unreliability of au...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/j.vascn.2017.09.254
更新日期：2017-01-01 00:00:00
abstract：:Lipid peroxidation is a major consequence of oxidative stress and an important cause of neuronal damage in ischaemic injuries and neurodegenerative disorders such as Parkinson's disease. Recent research has focused on the development of antioxidant drugs which may delay or minimize neurodegeneration. Rapid and reliabl...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(98)00022-7
更新日期：1998-04-01 00:00:00
abstract：INTRODUCTION:A variety of in vitro tests to replace the Draize test have been developed; however, there is no available method for assessing the full spectrum of Globally Harmonized System (GHS) categories. Human cornea-like three-dimensional (3D) reconstructed tissue models are the most promising in vitro systems. The...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2018.02.007
更新日期：2018-01-01 00:00:00
abstract：INTRODUCTION:Reversible protein cysteine oxidation is recognised as a pivotal post-transitional modification that transduces physiological as well as pathological signalling. Pharmacological interventions that target specific sources of oxidant formation are currently being trialled to ascertain their potential ability...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2013.07.001
更新日期：2013-11-01 00:00:00
abstract：INTRODUCTION:Dipeptidyl peptidases (DPPs) 8 and 9 are homologous, cytoplasmic postproline-cutting enzymes, which have similar enzymatic activity and preferred substrates as DPP4. DPP4 is a well-known target for treating diabetes mellitus. With the increased concern of non-selectivity and toxicities caused by DPP4 inhib...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2014.11.002
更新日期：2015-01-01 00:00:00
abstract：:Electroencephalogram (EEG) data in nonclinical species can play a critical role in the successful evaluation of a compound during drug development, particularly in the evaluation of seizure potential and for monitoring changes in sleep. Yet, while non-invasive electrocardiogram (ECG) monitoring is commonly included in...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/j.vascn.2016.03.002
更新日期：2016-09-01 00:00:00
abstract：INTRODUCTION:IonWorks automated patch clamp systems are being widely used for ion channel drug discovery, but the perforated patch mode of these systems makes it difficult to obtain a steady intracellular Ca(2+) concentration ([Ca(2+)](i)). This difficulty prevents obtaining high-quality data regarding Ca(2+)-activated...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2012.10.005
更新日期：2013-01-01 00:00:00
abstract：INTRODUCTION:Different methods for the analysis of behavioral observation data were compared to evaluate how the interpretation of a data set may depend on the analysis method employed. METHODS:Three methods of analysis were used to evaluate the same four sets of rodent behavioral FOB data: (1) evaluation by a trained...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2010.06.001
更新日期：2010-09-01 00:00:00
abstract：:The clinical value of coronary vasodilators in antianginal therapy depends on the ratio of their epicardial versus resistance coronary vessel actions. The coronary flow measured in standard isolated heart preparations, however, does not allow any conclusion about the function of epicardial vessels. Thus, we establishe...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(97)00096-8
更新日期：1997-12-01 00:00:00
abstract：INTRODUCTION:Drug-induced prolongation of the electrocardiographic QT interval (long QT syndrome) has been associated with increased risk of a serious ventricular arrhythmia, torsade de pointes. Inhibition of hERG, a cardiac potassium channel that controls action potential repolarization, is the most common cause of QT...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2008.10.004
更新日期：2009-01-01 00:00:00
abstract：:A wipe sampling procedure followed by a simple ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneous quantification of six cytotoxic drugs: 5-fluorouracil (5FU), doxorubicin (DOXO), epirubicin (EPI), ifosfamide (IF), cyclophosphamide (CP) an...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2019.106652
更新日期：2020-01-01 00:00:00
abstract：INTRODUCTION:Quantification of lactate dehydrogenase (LDH) release is a widely accepted assay for the quantitative determination of cell viability and late-stage apoptosis. Major disadvantages of commercially available LDH assay kits include proprietary formulations, limited options for optimization and high cost, all ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2015.02.001
更新日期：2015-05-01 00:00:00
abstract：:The pre-marketing testing of drugs and chemicals is now a paradigm of contribution to the safeguard of public health. As pointed out by the ICH concept paper E14/S7B, there is a need for science-based frameworks that allow a better design, conduction, and interpretation of nonclinical and toxicity tests, particularly,...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2020.106684
更新日期：2020-01-01 00:00:00
abstract：INTRODUCTION:Drug-induced cardiovascular effects identified in conscious cynomolgus monkeys equipped with tethers and prepared for radiotelemetry were compared with results from anesthetized non-human primate (cynomolgus and rhesus) models. METHODS:Remifentanil (4.0 microg/kg, bolus), esmolol (2.0 mg/kg, bolus) and do...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2008.05.004
更新日期：2008-09-01 00:00:00
abstract：INTRODUCTION:The standard Ficoll-Hypaque method used to isolate peripheral blood mononuclear cells (PBMC) gives very variable results when used with cynomolgus monkey blood. We have improved the method by using special cell processing tubes (CP-tubes), originally developed for clinical use. METHODS:Blood samples were ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2004.04.003
更新日期：2004-09-01 00:00:00
abstract：INTRODUCTION:Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2005.02.003
更新日期：2006-01-01 00:00:00
abstract：INTRODUCTION:The purpose of this study was: (1) to characterize and assess the incidence of spontaneous arrhythmias in totally naive Beagle dogs (n=51; 10 males+41 females): (2) to study the effects of permanent ECG- and LVP-probe telemetry implants both acutely and up to 233days after surgery in a subset of 11 female ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2011.04.001
更新日期：2011-07-01 00:00:00
