Quantitative Structure-Activity Relationships of Chemicals Acting by Non-polar Narcosis—Theoretical Considerations

Abstract

Theoretical quantitative structure-activity relationships have been established based on narcotic mechanisms of action and toxicity data to the fathead minnow, Daphnia magna and Vibrio ®scheri. The results con®rmed that hydrophobicity is important in modelling narcosis. However, the results of the present investigation also con®rmed that molecular bulk may play an important role in toxicity to aqueous organisms, especially in the toxicity to organisms with lower lipid content, for example, V. ®scheri. The results are discussed in the light of other inter-species differences that may occur as a consequence of accumulation and clearance kinetics and the relative metabolism of xenobiotics by each organism. Because of the complex tissue structure of organisms, classi®cation of narcotic compounds using hydrophobicity parameters alone can sometimes lead to errors.Abbreviations: QSAR, quantitative structure-activity relationship; P, 1-octanolawater partition coef®cient; Vx, McGowan characteristic volume; Vi, Leahy's intrinsic volume; V M , molar volume; BCF, bioconcentration factor; EC 50 , concentration causing 50% inhibition of bioluminescence to Vibrio ®scheri; IC 50 , immobilisation concentration for 50% of Daphnia magna at 24 hours; LC 50 , lethal concentration for 50% of fathead minnow at 96 hours.

Data Quality in the Human and Environmental Health Sciences: Using Statistical Confidence Scoring to Improve QSAR/QSPR Modeling

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Discrimination of excess toxicity from narcotic effect: Influence of species sensitivity and bioconcentration on the classification of modes of action

“…The concentration values causing a 50% inhibition of bioluminescence after 15 or 30 min exposure to V. fischeri (expressed as IBC 50 ) for 1239 compounds were taken mainly from several references (Kaiser and Palabrica, 1991;Cronin et al, 2000;Zhao et al, 1998;Terasaki et al, 2009;Dearden et al, 2000;Aruoja et al, 2011;Jones et al, 2011;Qin et al, 2010;Shi et al, 2012;Villa et al, 2012). No significant difference was observed in the two toxicity endpoints.…”

Toxicity of substituted benzenes and algae (Scenedesmus obliquus) with solvation equation

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“…Toxicity data and some molecular descriptorsThe test set is compounds3,7,8,18,21,25,26, 30, 32, 33. The rest of the compounds are the training set.…”