Reproducibility of toxicity across mode of toxic action in the Tetrahymena population growth impairment assay

Seward, Julie R.; Sinks, Glendon D.; Schultz, T.W.

doi:10.1016/s0166-445x(00)00158-2

Cited by 33 publications

(25 citation statements)

References 34 publications

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“…There are modulating effects coming from the molecular environment surrounding the reactive centre, and in case of previously unknown functionality the classification becomes very difficult. Finally, the variability in toxicity data was found to be higher for reactive chemicals than for narcotics [61].…”

Section: (Q)sar Models For Other Modes Of Actionmentioning

confidence: 93%

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Review of (Quantitative) Structure–Activity Relationships for Acute Aquatic Toxicity

2008

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This paper reviews different approaches described in the literature for estimating the aquatic toxicity of chemical substances. It is based on an extended review performed by the European Chemicals Bureau of the European Commissions Joint Research Centre in support of the development of technical guidance for the implementation of the REACH legislation, and is one of a series of minireviews in this journal. The paper is organised by approach for (Q)SAR development and includes a review of: (i) (Q)SARs for acute aquatic toxicity by chemical class, (ii) (Q)SARs for acute aquatic toxicity by mode of action, (iii) review of statistically derived (Q)SARs, (iv) structural alerts for excess aquatic toxicity and (v) expert systems that combine structural rules and multiple (Q)SAR models to predict aquatic toxicological endpoints. Directions and recommendations for further research are also provided.

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Section: (Q)sar Models For Other Modes Of Actionmentioning

confidence: 93%

“…The classification of chemicals according to mode/mechanism of action is not an easy task [61]. Experimental methods for classification exist (e.g.…”

Section: Classification According To Mode Of Actionmentioning

confidence: 99%

Review of (Quantitative) Structure–Activity Relationships for Acute Aquatic Toxicity

2008

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“…More complicated factors could include different mechanisms of actions of molecules, e.g. chemicals considered as reactive were reported to have about two times higher variability of measurements compared to those thought to have a narcosis mode of action for the toxicity against T. Pyriformis [9]. For example, descriptor x 2 can have, e.g.…”

Section: Analysis Of a Distance To Models Using Simulated Examplesmentioning

confidence: 99%

“…In our previous study, we have developed several models to predict this environmental toxicity using a dataset of 1093 compounds [16] with data measured by Schultz and co-authors [9,[20][21][22]. We have benchmarked several DM definitions with respect to their performance to distinguish molecules with low and high prediction accuracies [10].…”

Section: Modeling Of Environmental Toxicity Against T Pyriformismentioning

confidence: 99%

Applicability domain for in silico models to achieve accuracy of experimental measurements

Sushko

Novotarskyi

Körner

et al. 2010

Journal of Chemometrics

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The accuracy of in silico models can be inhomogeneous: models can show excellent performance on some chemical subspaces but have low accuracy on others. We show that applicability domain (AD) approaches can differentiate reliable and non-reliable predictions and identify those with experimental accuracy for both regression and classification models. For reliably predicted molecules, the predicted values can be used instead of experimental measurements. This can halve time and costs of experimental measurements. The developed classification models for AMES mutagenicity test and CYP450 inhibition, which are important drug discovery properties, are publicly available at the online chemical database and modeling environment (OCHEM) site http://qspr.eu

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“…However, even within a single test, there is varying reproducibility between toxicants. Seward et al [23], in an investigation of T. pyriformis toxicity data, found that error on the measured values was greater for chemicals considered to be electrophilic than on others thought to act via narcosis.…”

Section: Dataset Should Be Both Structurally and Potency Diversementioning

confidence: 99%

Essential and desirable characteristics of ecotoxicity quantitative structure–activity relationships

Schultz

Cronin

2003

Enviro Toxic and Chemistry

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Quantitative structure-activity relationships (QSAR) developed and applied in the prediction of ecotoxic potencies far out number those in other areas, such as health effects. There are yet to be any formal guidelines for the development of ecotoxicological QSARs. Despite this, the depth and breadth of our knowledge of QSARs as they apply to ecotoxicology, especially short-term aquatic toxicity, allow for the formulation of characteristics that appear to be essential and/or desirable for high-quality QSARs. The three components of a QSAR are the biological activity, the property/structural descriptors, and the statistical methodology. Problems may arise from all three components and may be compounded by interactions between them. In an effort to minimize any tribulations associated with development and application of ecotoxic QSARs, a number of essential or desirable characteristics have been identified. Ecotoxicological data used in formulating the QSAR must be reliable, of high quality, and reflect a well-defined and continuous endpoint; this dataset should be diverse both in terms of potency and chemical structure (i.e., property). Descriptors used in formulating the QSAR should be of high quality, reproducible, of a number and type consistent with the endpoint being modeled, and when possible allow for a mechanistic interpretation of the QSAR. The statistical process used in formulating a QSAR should be as rigorous as possible, appropriate for the endpoint being modeled, and allow for the development of as easily interpretable (i.e., transparent) QSARs as possible. The resultant QSAR should be validated, only used within the descriptor space and chemical domain of the model, and relied on in relation to the total weight of evidence; precision of the QSAR and expectations from its application need to be related to the error in the original ecotoxicological and descriptor measurements. Finally, development of QSARs should be through the interaction of a group of multidisciplinary experts.

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Reproducibility of toxicity across mode of toxic action in the Tetrahymena population growth impairment assay

Cited by 33 publications

References 34 publications

Review of (Quantitative) Structure–Activity Relationships for Acute Aquatic Toxicity

Review of (Quantitative) Structure–Activity Relationships for Acute Aquatic Toxicity

Applicability domain for in silico models to achieve accuracy of experimental measurements

Essential and desirable characteristics of ecotoxicity quantitative structure–activity relationships

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