Journal ArticleDOI
Reactivity and aquatic toxicity of aromatic compounds transformable to quinone-type Michael acceptors
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TLDR
The reactivity of potential pre-electrophile polyphenolics was investigated using an in chemico assay based on glutathione depletion and the toxicity to Tetrahymena pyriformis was determined; no direct relationship between toxic potency and reactivity to GSH was obtained.Abstract:
Reactive toxicity encompasses important endpoints such as skin and respiratory sensitization, hepatotoxicity and elevated acute aquatic toxicity. These adverse effects are initiated by, among others, electrophilic chemicals and those transformed into electrophiles; i.e. non-reactive chemicals activated into reactive electrophilic species by either a biotransformation (pro-electrophiles) or abiotic mechanism (pre-electrophiles). The presence of pro- and pre-electrophiles is important when developing quantitative structure–activity relationships (QSARs). In this study, the reactivity of potential pre-electrophile polyphenolics was investigated using an in chemico assay based on glutathione (GSH) depletion; in addition, the toxicity to Tetrahymena pyriformis was determined. For pre-electrophiles, no direct relationship between toxic potency and reactivity to GSH was obtained. The structural determinants for the pre-electrophile domain were characterized qualitatively by assessing structure–activity relations...read more
Citations
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A review of the electrophilic reaction chemistry involved in covalent protein binding relevant to toxicity.
TL;DR: The literature defining the structural alerts associated with covalent protein binding and the associated electrophilic reaction chemistry are reviewed and incorporated into the OECD (Q)SAR Toolbox, a freely available software tool designed to fill data gaps in a regulatory environment without the need for further animal testing.
Journal ArticleDOI
Inhibition of urease activity by different compounds provides insight into the modulation and association of bacterial nickel import and ureolysis.
TL;DR: This report reports the first comprehensive comparison of the inhibition of urease activity by compounds analysed under the same conditions, and finds that carbon disulfide, N-phenylmaleimide, diethylenetriaminepentaacetic acid, sodium pyrrolidinedithiocarbamate, and 1,2,4-butanetricarboxylic acid have not previously been reported to possess anti-ureolytic properties.
Journal ArticleDOI
Molecular fingerprint-derived similarity measures for toxicological read-across: Recommendations for optimal use.
Claire L. Mellor,R.L. Marchese Robinson,Romualdo Benigni,D.J. Ebbrell,Steven J. Enoch,James W. Firman,Judith C. Madden,Gopal Pawar,Chihae Yang,Mark T. D. Cronin +9 more
TL;DR: This study investigated the value and concordance of the Tanimoto similarity values calculated using six widely used fingerprints within six toxicological datasets and suggested generic fingerprint‐derived similarities are likely to be optimally predictive for local datasets, i.e. following sub‐categorisation.
Journal ArticleDOI
Investigation of the Verhaar scheme for predicting acute aquatic toxicity: Improving predictions obtained from Toxtree ver. 2.6
TL;DR: Modifications to the implementation of Verhaar between version 1.5 and 2.6 of Toxtree have improved performance by reducing the number of incorrectly classified compounds, and the utility of the modification described herein is demonstrated through building quality, mechanism-specific Quantitative Structure Activity Relationship (QSAR) models for the compounds within specific mechanistic categories.
Journal ArticleDOI
Self-Propelled Micromotors for Naked-Eye Detection of Phenylenediamines Isomers.
TL;DR: Self-propelled micromotors act as peroxidase-like mobile platforms that offer efficient phenylenediamines detection and discrimination in just 15 min and hold considerable promise for its application in sensing systems in a myriad of environmental, industrial, and health applications.
References
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Mechanistic Applicability Domains for Nonanimal-Based Prediction of Toxicological End Points: General Principles and Application to Reactive Toxicity
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Journal Article
Sequential oxidation and glutathione addition to 1,4-benzoquinone: correlation of toxicity with increased glutathione substitution.
TL;DR: The conjugation of glutathione with quinones does not necessarily result in detoxification, even when the resulting conjugates are more stable to oxidation, and the inhibition of gamma-glutamyl transpeptidase by AT-125 protected against 2,3,5-(triglutathion-S-yl)hydroquinone-mediated nephrotoxicity.
Journal ArticleDOI
A conceptual framework for predicting the toxicity of reactive chemicals: modeling soft electrophilicity.
Terry W Schultz,R E Carlson,Mark T. D. Cronin,Joop L. M. Hermens,R Johnson,Peter J. O'Brien,David W. Roberts,Arno G. Siraki,Kendall B. Wallace,Gilman D. Veith +9 more
TL;DR: Empirical measures of the chemical reactivity of xenobiotics with a model nucleophile are used to simulate the relative rates at which a reactive chemical is likely to bind irreversibly to cellular targets.