Journal ArticleDOI
Evaluation of the OECD QSAR Application Toolbox and Toxtree for estimating the mutagenicity of chemicals. Part 1. Aromatic amines
James Devillers,Enrico Mombelli +1 more
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TLDR
The Ames Salmonella typhimurium mutagenicity assay was re-computed to check its transparency and to verify its statistical validity and about 150 chemicals not previously used for the design of the model but belonging to its domain of application were tested.Abstract:
The Ames Salmonella typhimurium mutagenicity assay is a short-term bacterial reverse mutation test that was designed to detect mutagens. For several decades, it has been used in research laboratories and by regulatory agencies throughout the world for the detection and characterization of potential mutagens among natural products and man-made chemicals. Faced with the ever-growing number of chemicals available on the market, congeneric and non-congeneric (Q)SAR models have been designed from Ames test results obtained on specific S. typhimurium strains such as TA 100 or TA 98. Such models have great potential for a quick and cheap identification and classification of large numbers of potential chemical mutagens. The OECD QSAR Application Toolbox and Toxtree, which were developed for facilitating the practical use of (Q)SAR approaches in regulatory contexts, include two mechanistic SAR models for predicting the mutagenicity of aromatic amines and - unsaturated aliphatic aldehydes. The aim of this study was to estimate the interest and limitations of the former model. The model was first re-computed to check its transparency and to verify its statistical validity. Then, it was tested on about 150 chemicals not previously used for the design of the model but belonging to its domain of application. A critical analysis of the results was performed and proposals were made for increasing the model performances.read more
Citations
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Journal ArticleDOI
QSAR Modeling is not "Push a Button and Find a Correlation": A Case Study of Toxicity of (Benzo-)triazoles on Algae.
Paola Gramatica,Stefano Cassani,Partha Pratim Roy,Partha Pratim Roy,Simona Kovarich,Chun Wei Yap,Ester Papa +6 more
TL;DR: This work summarizes a methodology for a rigorous statistical approach to obtain reliable QSAR predictions, also for a large number of (B)TAZs in the ECHA preregistration list of REACH (even if starting from limited experimental data availability), and has evidenced some ambiguities and discrepancies related to SMILES notations from different databases.
Journal ArticleDOI
In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts.
TL;DR: This research presents a novel probabilistic procedure called “spot-spot analysis” that allows for real-time analysis of the response of the immune system to Epstein-Barr virus.
Journal ArticleDOI
Use of in silico systems and expert knowledge for structure-based assessment of potentially mutagenic impurities
Andreas Sutter,Alexander Amberg,Scott Boyer,Alessandro Brigo,Joseph F. Contrera,Laura Custer,Krista L. Dobo,Véronique Gervais,Susanne Glowienke,Jacky Van Gompel,Nigel Greene,Wolfgang Muster,John Nicolette,M. Vijayaraj Reddy,Véronique Thybaud,Esther Vock,Angela White,Lutz Müller +17 more
TL;DR: The procedures presented here for structure-based assessment are considered appropriate for regulatory submissions in the scope of ICH M7 and a rule-based expert system complemented by either expert knowledge or a second (Q)SAR model is appropriate.
Journal ArticleDOI
Ethics of animal research in human disease remediation, its institutional teaching; and alternatives to animal experimentation
TL;DR: This treatise compactly cover the basics of animal research ethics, ethical reviewing and compliance guidelines for animal experimentation across the developed world, “the authors'” fundamentals of institutional animal research research ethics teaching, and emerging alternatives to animal research.
References
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Journal ArticleDOI
Salmonella mutagenicity test results for 250 chemicals
TL;DR: This publication is a presentation of Salmonella testing results on 250 coded chemicals, encompassing 370 tests, designed both to summarize the results in the text and to present the data so that the reader has the opportunity of performing an independent evaluation of the data.
Journal ArticleDOI
Aromatic amines and cancer
Paolo Vineis,Roberta Pirastu +1 more
TL;DR: The consistent observation of a difference between men and women in bladder cancer risk, after allowing for known risk factors, suggests consideration of gender-related biological determinants for future investigation.
Journal ArticleDOI
Structure alerts for carcinogenicity, and the Salmonella assay system: a novel insight through the chemical relational databases technology.
Romualdo Benigni,Cecilia Bossa +1 more
TL;DR: Recent analyses on the predictive performance of various lists of structure alerts are reviewed, including a new compilation of alerts that combines previous work in an optimized form for computer implementation and the use of structural alerts for the chemical biological profiling of a large database of Salmonella mutagenicity results is reported.
Journal ArticleDOI
Genotoxic activity and potency of 135 compounds in the Ames reversion test and in a bacterial DNA-repair test
TL;DR: The genotoxic potencies in the two bacterial systems were correlated within the majority of the chemical classes under scrutiny, and the genot toxic potency varied over a 4.5 X 10(7)-fold range among compounds positive in the reversion test and over a 6X 10(9)-foldrange among compounds damaging E. coli DNA.
The Benigni / Bossa rulebase for mutagenicity and carcinogenicity - a module of Toxtree
TL;DR: This report gives an introduction to currently available QSARs and SAs for carcinogenicity and mutagenicity, and provides details of the Benigni/Bossa rulebase.
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