Predicting Modes of Toxic Action From Chemical Structure: Acute Toxicity in the Fathead Minnow (Pimephales Promelas)

Russom, Christine L.; Bradbury, Steven P.; Broderius, Steven J.; Hammermeister, Dean E.; Drummond, Robert A.

doi:10.1897/1551-5028(1997)016<0948:pmotaf>2.3.co;2

Cited by 293 publications

(329 citation statements)

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“…To complete the classification, they were further profiled with Toxtree and the post-processing filter encoded as a KNIME workflow (Ellison et al 2015) that has recently been developed in order to improve the predictivity of the Toxtree software. In case of conflicting results or MOA 5 chemicals, other data from the literature has been used to attribute a final MOA (Barron, Lilavois, and Martin 2015;ECETOC 2007;Russom et al 1997).…”

Section: Assignment Of Modes Of Actionmentioning

confidence: 99%

Waiving chronic fish tests: possible use of acute-to-chronic relationships and interspecies correlations

Kienzler

Halder

Worth

2016

Toxicological & Environmental Chemistry

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EU chemicals legislation requires the use of all available information for hazard and risk assessment before new tests on vertebrates are proposed or conducted. In this context, extrapolation approaches for avoiding chronic fish testing on the basis of existing data have been explored. Simple linear relationships and interspecies sensitivity ratios between Daphnia and fish were calculated and acute-to-chronic relationships and ratios were calculated for fish, taking into consideration the mode of action. The best fitted relationships for the prediction of chronic fish toxicity are obtained based on acute fish and Daphnia data. Chemicals acting by unspecific reactivity and non-polar narcosis give the strongest acute and chronic Daphnia-to-chronic fish relationship. With acute fish data, strong relationships are obtained for all mode of action. Daphnia was found to be more sensitive than fish to several aniline derivatives and pesticides acting through cholinesterase inhibition, and less sensitive than fish to known endocrine disruptors. Extreme (i.e. <1 or >100) interspecies sensitivity ratios were mainly evident for chemicals acting by polar narcosis and specific reactivity. The safety factor of 100 commonly applied in environmental risk assessment does not seem to be equally protective for each mode of action.

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Section: Assignment Of Modes Of Actionmentioning

confidence: 99%

Waiving chronic fish tests: possible use of acute-to-chronic relationships and interspecies correlations

Kienzler

Halder

Worth

2016

Toxicological & Environmental Chemistry

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“…One typical approach is employed in the commercial system LHASA [1], which compiles empirical knowledge with QSAR results in toxicology and uses an expert system framework to predict the toxic effects of a new compound. Characteristic substructures of dopamine agonists have been extracted based on purely empirical considerations [2].…”

Section: Introductionmentioning

confidence: 99%

The development of a knowledge base for basic active structures: an example case of dopamine agonists

Okada

Yamakawa

Ohmori

et al. 2010

Chemistry Central Journal

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BackgroundChemical compounds affecting a bioactivity can usually be classified into several groups, each of which shares a characteristic substructure. We call these substructures "basic active structures" or BASs. The extraction of BASs is challenging when the database of compounds contains a variety of skeletons. Data mining technology, associated with the work of chemists, has enabled the systematic elaboration of BASs.ResultsThis paper presents a BAS knowledge base, BASiC, which currently covers 46 activities and is available on the Internet. We use the dopamine agonists D1, D2, and Dauto as examples and illustrate the process of BAS extraction. The resulting BASs were reasonably interpreted after proposing a few template structures.ConclusionsThe knowledge base is useful for drug design. Proposed BASs and their supporting structures in the knowledge base will facilitate the development of new template structures for other activities, and will be useful in the design of new lead compounds via reasonable interpretations of active structures.

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“…Corresponding Balanced Accuracy values of the developed models varied in the range from 0.85 to 0.93. A number of studies [85,86] with the regression analysis have been published including the original publication of this data set [61]. The carcinogenicity data involved in this study has been used in QSAR studies mostly as a source of further data retrieval.…”

Section: Resultsmentioning

confidence: 99%

“…Data from EPA Fathead Minnow Acute Toxicity Database [61] after data preparation stage containing 612 compounds (578 actives and 34 inactives). This database was generated by the U.S. EPA Mid-Continental Ecology Division (MED) for the purpose of developing an expert system to predict acute toxicity from chemical structures based on mode of action considerations.…”

Section: Methodsmentioning

confidence: 99%

Supervised extensions of chemography approaches: case studies of chemical liabilities assessment

et al. 2014

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Chemical liabilities, such as adverse effects and toxicity, play a significant role in modern drug discovery process. In silico assessment of chemical liabilities is an important step aimed to reduce costs and animal testing by complementing or replacing in vitro and in vivo experiments. Herein, we propose an approach combining several classification and chemography methods to be able to predict chemical liabilities and to interpret obtained results in the context of impact of structural changes of compounds on their pharmacological profile. To our knowledge for the first time, the supervised extension of Generative Topographic Mapping is proposed as an effective new chemography method. New approach for mapping new data using supervised Isomap without re-building models from the scratch has been proposed. Two approaches for estimation of model’s applicability domain are used in our study to our knowledge for the first time in chemoinformatics. The structural alerts responsible for the negative characteristics of pharmacological profile of chemical compounds has been found as a result of model interpretation.

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Predicting Modes of Toxic Action From Chemical Structure: Acute Toxicity in the Fathead Minnow (Pimephales Promelas)

Cited by 293 publications

References 0 publications

Waiving chronic fish tests: possible use of acute-to-chronic relationships and interspecies correlations

Waiving chronic fish tests: possible use of acute-to-chronic relationships and interspecies correlations

The development of a knowledge base for basic active structures: an example case of dopamine agonists

Supervised extensions of chemography approaches: case studies of chemical liabilities assessment

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