A5057052925- Computational Drug Discovery Methods
- Animal testing and alternatives
- Pesticide Exposure and Toxicity
- Environmental Toxicology and Ecotoxicology
- Effects and risks of endocrine disrupting chemicals
- Chemistry and Chemical Engineering
- Analytical Chemistry and Chromatography
- Chemical Safety and Risk Management
- Agricultural safety and regulations
- Cholinesterase and Neurodegenerative Diseases
- Environmental Chemistry and Analysis
- Toxic Organic Pollutants Impact
- Lipid Membrane Structure and Behavior
- Carcinogens and Genotoxicity Assessment
- bioluminescence and chemiluminescence research
- Pesticide and Herbicide Environmental Studies
- Molecular Sensors and Ion Detection
- Various Chemistry Research Topics
- Insect and Pesticide Research
- Public Administration, ICT, and Policy Development
- Advanced Chemical Sensor Technologies
- Genetics, Aging, and Longevity in Model Organisms
- Plant biochemistry and biosynthesis
- Gene Regulatory Network Analysis
- Electrochemical Analysis and Applications
Unilever (United Kingdom)
2014-2023
University of Bedfordshire
2011-2023
Vitenparken
2020
Kelly Services (United States)
2018
The Bristol-Myers Squibb Children's Hospital
2018
In-Q-Tel
2013
The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates information needed for support predictions major toxicological endpoints concern (e.g., genetic toxicity, carcinogenicity, acute reproductive developmental toxicity) regulatory bodies. Such novel (IST)...
Consumer and environmental safety decisions are based on exposure hazard data, interpreted using risk assessment approaches. The adverse outcome pathway (AOP) conceptual framework has been presented as a logical sequence of events or processes within biological systems which can be used to understand effects refine current practices in ecotoxicology. This also applied human toxicology is explored the basis investigating molecular initiating (MIEs) compounds. precise definition MIE yet reach...
The adverse outcome pathway (AOP) framework provides an alternative to traditional in vivo experiments for the risk assessment of chemicals. AOPs consist a number key events (KEs) linked by event relationships across range biological organization backed scientific evidence. first KE is molecular initiating (MIE)-the initial chemical trigger that starts AOP. Over past 3 years AOP conceptual has gained large amount momentum toxicology as animal methods, and so MIE come into spotlight. What...
The threshold of toxicological concern (TTC) concept is well established for assessing human safety food-contact substances and has been reapplied a variety endpoints, including carcinogenicity, teratogenicity, reproductive toxicity. TTC establishes an exposure level chemicals below which no appreciable risk to health or the environment expected, based on de minimis value toxicity identified many chemicals. Threshold approaches have benefits screening-level assessments, potential rapid...
The Adverse Outcome Pathway (AOP) conceptual framework has been presented as a logical sequence of events or processes within biological systems which can be used to understand adverse effects and refine the current risk assessment practice. This approach shifts focus from traditional apical endpoints development mechanistic understanding chemicals effect at molecular cellular level. In order obtain this level detail, chemistry in all its disciplines key role play. Measurement techniques...
Molecular initiating events (MIEs) are important concepts for in silico predictions. They can be used to link chemical characteristics biological activity through an adverse outcome pathway (AOP). In this work, we capture 2D structural alerts, which then as models predict MIEs. An automated procedure has been identify these and the categories they define have provide quantitative predictions of molecules that contain them. This done across a diverse group 39 pharmacological human targets...
Chemoinformatics has been successfully employed in safety assessment through various regulatory programs for which information from databases, as well predictive methodologies including computational methods, are accepted. One example is the European Union Cosmetics Products Regulations, Europe (CE) research activities non-animal methods have managed by Long Range Science Strategy (LRSS) program. The vision to use mechanistic aspects of existing New Approach Methodologies (NAMs), demonstrate...
Deep learning neural networks, constructed for the prediction of chemical binding at 79 pharmacologically important human biological targets, show extremely high performance on test data (accuracy 92.2 ± 4.2%, MCC 0.814 0.093, ROC-AUC 0.96 0.04).
Structure-activity relationships (SARs) in toxicology have enabled the formation of structural rules which, when coded as alerts, are essential tools silico toxicology. Whilst other methods approaches for their evaluation, there is no formal process to assess confidence that may be associated with a alert. This investigation proposes twelve criteria uncertainty allowing an assessment confidence. The based around stated purpose, description chemistry, and mechanism, performance coverage, well...
A molecular initiating event (MIE) is the gateway to an adverse outcome pathway (AOP), a sequence of events ending in effect. In silico predictions MIEs are vital tool modern, mechanism-focused approach chemical risk assessment. For 90 biological targets representing important human MIEs, structural alert-based models have been constructed with automated procedure that uses Bayesian statistics iteratively select substructures. These give impressive average performance (an 92% correct across...
The contribution of each CH<sub>x</sub> unit to the overall membrane sorption affinity an organic cation depends on most favorable orientation sorbed molecule in bilayer.
Molecular initiating events (MIEs) can be boiled down to chemical interactions. Chemicals that interact must have intrinsic properties allow them exhibit this behavior, these stereochemical, electronic, or otherwise. In an attempt discover some of characteristics, we constructed structural alert-style structure–activity relationships (SARs) computationally predict MIEs. This work utilizes informatics approaches, searching the ChEMBL database for molecules bind a number pharmacologically...
The aim of human toxicity risk assessment is to determine a safe dose or exposure chemical for humans. This requires an understanding the person and how much required cause adverse effect. To do this computationally, we need understand perturb normal biological function in outcome pathway (AOP). molecular initiating event (MIE) first step can be considered as interaction between toxicant molecule. Key characteristics identified used model chemistry these MIEs. In study, just by using...
Quantitative structure-activity relationship (QSAR) modelling of aquatic toxicity for cationic surfactants has received limited attention despite the fact that this type are generally more toxic than predicted by general narcosis or polar equations. Here we report measurement log P three types aromatic quaternary ammonium halides at sub-micellar concentrations, refinement earlier rules calculation, and development a hydrophobicity based QSAR, using both calculated measured values, to Daphnia...
The sorption affinity of eighty-six charged amine structures to phospholipid monolayers (log KIAM) was determined using immobilized artificial membrane high-performance liquid chromatography (IAM-HPLC). compounds covered the most prevalent types polar groups, widely ranged in structural complexity, and included forty-seven pharmaceuticals, as well several narcotics pesticides. Amine type specific corrective increments were used align log KIAM data with bilayer coefficients (KMW(IAM)). Using...
The Ames mutagenicity assay is a long established in vitro test to measure the potential of new chemical used regulatory testing globally. One key computational approaches modeling relies on formation categories based different electrophilic compounds that are able react directly with DNA and form covalent bond. Such sometimes predict false positives, as not all Michael acceptors found be Ames-positive. such bonds can explored computationally using density functional theory transition state...
This study developed a novel classification scheme to assign chemicals verifiable mechanism of (eco-)toxicological action allow for grouping, read-across, and in silico model generation. The new unifies extends existing schemes has, at its heart, direct reference molecular initiating events (MIEs) promoting adverse outcomes. is based on three broad domains toxic representing nonspecific toxicity (e.g., narcosis), reactive mechanisms electrophilicity free radical action), specific associated...
The concept of thresholds toxicological concern as a potentially useful tool in environmental risk assessment has been applied to the inventory home and personal care products company derive series chemical class-based ecotoxicological threshold (ecoTTC) values. Cationic chemicals various types show notably higher toxicity than other classes should be treated separately. Despite this, ecoTTC for full data set present study is only slightly lower that derived previously causing via Verhaar...
Molecular initiating events (MIEs) are key in adverse outcome pathways that link molecular chemistry to target biology. As they based on chemistry, these interactions excellent targets for computational approaches silico modeling. In this work, we aim ligand chemical structures MIEs androgen receptor (AR) and glucocorticoid (GR) binding using ToxCast data. This has been done an automated algorithm perform maximal common substructure searches binders each from the dataset. The models...