Taft Sigma and Sigma, Constants Improve Log Octanol/Water Partition Coefficient Based QSAR for Fathead Minnow Toxicity

Purdy, Rich

doi:10.1007/978-94-009-3937-0_21

Cited by 7 publications

(7 citation statements)

References 7 publications

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“…Historically, QSAR approaches for electrophiles used the Hammett substituent constant σ. 35 More recently, molecular orbital descriptors have been used. Namely the molecule-based descriptor E lumo 31,36 and the atom-centered maximum acceptor superdelocalizability A max .…”

Section: Discussionmentioning

confidence: 99%

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Response-Surface Analyses for Toxicity to Tetrahymena pyriformis: Reactive Carbonyl-Containing Aliphatic Chemicals

Schultz

Cronin

1999

J. Chem. Inf. Comput. Sci.

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A response-plane has been developed with Tetrahymena pyriformis population growth impairment toxicity data [log 1/50% growth inhibitory concentration (IGC50)], the 1-octanol/water partition coefficient (log Kow), and the energy of the lowest unoccupied molecular orbital (Elumo). A statistically robust plane [log 1/IGC50 = 0.530 (log Kow) -0.890 (Elumo) -0.271, n = 50, s = 0.295, r2 = 0.855, F = 145] was found for reactive carbonyl-containing aliphatic chemicals. These compounds had a variety of electrophilic mechanisms of action and included aldehydes acting as Schiff-base formers, alpha,beta-unsaturated aldehydes and alpha,beta-unsaturated ketones acting as Michael-type acceptors, and selected alpha-diones acting as selective binders to arganine residues; gamma-diones acting as selective binders to tubulin; and beta-diones with unknown mechanisms of action. Outliers to this model broadly fell into two groups: small reactive molecules (e.g., acrolein) that were more toxic than predicted and molecules in which the reactive center was sterically hindered by an alkyl group (e.g., 2,4-dimethyl-2,6-heptadienal) that were less toxic than predicted.

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Section: Discussionmentioning

confidence: 99%

“…In the past, the study of electro(nucleo)philic reactivity has been impeded by the lack of both experimental toxicity data and molecular-based descriptors. Historically, QSAR approaches for electrophiles used the Hammett substituent constant σ . More recently, molecular orbital descriptors have been used.…”

Section: Discussionmentioning

confidence: 99%

Response-Surface Analyses for Toxicity to Tetrahymena pyriformis: Reactive Carbonyl-Containing Aliphatic Chemicals

Schultz

Cronin

1999

J. Chem. Inf. Comput. Sci.

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“…Furthermore, compounds may have multiple modes of action. For such compounds, the use of inappropriate models will give inaccurate results and may underestimate the toxicity of compounds (McKim et al, 1987;Hunter et al, 1987;Hodson et al, 1988;Purdy, 1987).…”

Section: Introductionmentioning

confidence: 97%

“…In this case, we try to estimate the probable chemodynamics and effects of compounds based on known relationships between organisms of interest and other members of the class of compounds to which the compound of interest belongs. This is done by relating the functional properties of the class of compounds to toxicity by the use of quantitative structure activity relationships or QSAR for short (McKim et al, 1987;Wallace and Niemi, 1988;Hodson et al, 1988;Purdy, 1987;Lipnick et al, 1986;Thompson et al, 1987;Kaiser, 1987;Lipnick et al, 1985;Newsome et al, 1984;Newsome et al, 1987;Boethling et al, 1988;Kier and Hall, 1976;Hunter et al, 1987;Sampaolo and Binetti, 1986). Unfortunately, many old compounds other than pesticides have not been tested for their potential fate in the environment or toxicity to animals.…”

Section: Introductionmentioning

confidence: 98%

“…While not perfect, the QSAR technology allows screening for substances, which based on their chemical and physical properties will most likely be relatively toxic or relatively nontoxic (McKim et al, 1987;Wallace and Niemi, 1987;Hodson et al, 1988;Purdy, 1987;Kaiser, 1987;Newsome et al, 1984;Boethling et al, 1988). The use of a QSAR system is especially useful to screen large numbers of existing chemicals to identify those that are more likely to cause adverse environmental effects, to identify gaps in the existing fate and effects data and finally to identify and prioritize those chemicals on which limited resources for detailed studies of toxicity and/or environmental fate should be spent (Sampaolo and Binetti, 1986;Hunter et al, 1987;.…”

Section: Introductionmentioning

confidence: 99%

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Utility of the QSAR modeling system for predicting the toxicity of substances on the European inventory of existing commercial chemicals∗

Fiedler

Hutzinger

Giesy

1990

Toxicological & Environmental Chemistry

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Many chemicals are in common commercial use for which no information on the environmental fate or toxicity exists. Recent legislation requires that many substances be assessed for their toxicity to aquatic organisms within a very short time and determine which of these chemicals need to be studied in greater detail. It would be impossible to measure the acute and chronic effects of all of these compounds on a single organism, let alone a battery of different types of organisms, communities or ecosystems. Initially, the chemicals on the European Inventory of Existing Commercial Chemical Substances (EINECS) need to be screened and relative hazard to the environment determined. In response to OECD directives, there has been a great deal of activity by government and industry scientists. At the International Workshop on Advances in Environmental Hazard and Risk Assessment it was concluded that quantitative structure activity relationships (QSAR) could and should be used in the hazard assessment process. Papers published in that volume outline the advantages, disadvantages, limitations, advances and research requirements.The QSAR, structure-activity based chemical modeling and information system, which was developed by the US-Environmental Protection Agency was used to predict the acute toxicity of 113 substances from the "Old Substances" list of the German government to the four commonly used aquatic toxicity test organisms: Daphnia magna (DM), fathead minnow (FHM), rainbow trout (RBT), and blue-gill sunfish (BG).Of these compounds the QSAR system predicted the acute toxicity of 87 substances towards fathead minnow. For the other three species examined the QSAR system could be used to predict toxicity for 78 compounds.The predicted toxicities were compared to observed toxicities of compounds which have been evaluated and stored in the "Aquire" data base. Observed toxicity values were available for at least one species for 38 compounds. The toxicities of some compounds are well predicted while those of other compounds were not well predicted. Overall, the QSAR system accurately classified the acute toxicity ranges of 50%, 64%, 56% and 56% of the compounds investigated for DM, FHM, RBT and BG, respectively. Of the compounds studied 10 were very poorly predicted, of these the QSAR system overpredicted the toxicity of three, while underpredicting the toxicity of seven. Of these seven compounds, five contained amino groups.

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QSAR in Toxicology. 1. Prediction of Aquatic Toxicity

Cronin

Dearden

1995

Quant. Struct.‐Act. Relat.

148

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A critical review is given of quantitative and qualitative structureactivity relationships (QSAR) for the prediction of some acute aquatic toxicological endpoints. Consideration is given to sources of biological data and, as in all areas of toxicology, there is concern over the validity, quality and quantity of toxicological data to model. Despite these problems it is now possible to predict the acute aquatic toxicity of unreactive chemicals to many species with considerable accuracy. Predictions for other mechanisms of toxic action become less accurate as more specific toxicities are investigated. Surprisingly little work has been performed on the prediction of toxicity of inorganic elements and their complexes, to both aquatic species and other organisms.

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Taft Sigma and Sigma, Constants Improve Log Octanol/Water Partition Coefficient Based QSAR for Fathead Minnow Toxicity

Cited by 7 publications

References 7 publications

Response-Surface Analyses for Toxicity to Tetrahymena pyriformis: Reactive Carbonyl-Containing Aliphatic Chemicals

Response-Surface Analyses for Toxicity to Tetrahymena pyriformis: Reactive Carbonyl-Containing Aliphatic Chemicals

Utility of the QSAR modeling system for predicting the toxicity of substances on the European inventory of existing commercial chemicals∗

QSAR in Toxicology. 1. Prediction of Aquatic Toxicity

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