Quantitative structure–activity relationship analysis of acute toxicity of diverse chemicals to Daphnia magna with whole molecule descriptors

Abstract

Quantitative structure-activity relationship analysis and estimation of toxicological effects at lower-mid trophic levels provide first aid means to understand the toxicity of chemicals. Daphnia magna serves as a good starting point for such toxicity studies and is also recognized for regulatory use in estimating the risk of chemicals. The ECOTOX database was queried and analysed for available data and a homogenous subset of 253 compounds for the endpoint LC50 48 h was established. A four-parameter quantitative structure-activity relationship was derived (coefficient of determination, r (2) = 0.740) for half of the compounds and internally validated (leave-one-out cross-validated coefficient of determination, [Formula: see text] = 0.714; leave-many-out coefficient of determination, [Formula: see text] = 0.738). External validation was carried out with the remaining half of the compounds (coefficient of determination for external validation, [Formula: see text] = 0.634). Two of the descriptors in the model (log P, average bonding information content) capture the structural characteristics describing penetration through bio-membranes. Another two descriptors (energy of highest occupied molecular orbital, weighted partial negative surface area) capture the electronic structural characteristics describing the interaction between the chemical and its hypothetic target in the cell. The applicability domain was subsequently analysed and discussed.

Exploring the role of quantum chemical descriptors in modeling acute toxicity of diverse chemicals to Daphnia magna

“…The values for the descriptors log P mix , 1 BIC and WNSA-1, are taken from a previous study by Moosus and Maran [9]. The detailed calculations of these descriptors along with the corresponding relations are described in Moosus and Maran [9].…”

“…The values for the descriptors log P mix , 1 BIC and WNSA-1, are taken from a previous study by Moosus and Maran [9]. The detailed calculations of these descriptors along with the corresponding relations are described in Moosus and Maran [9]. It should be noted that log P mix refers to 1-octanol-water partition coefficient determined either experimentally or using atom/fragment contribution method implemented in KOWWIN estimation program of EPI suite [53].…”

“…The choice of these descriptors is based on the robust models available in the literature [Ref. [9] and references therein].…”

“…Therefore, the thirst for the externally predictive QSAR models for the acute toxicity of diverse chemicals towards the D. magna had been continued since many years [5][6][7][8]. In the literature [4,[9][10][11][12], the toxic effects of various hazardous chemicals towards D. magna, have been modeled mainly through the physico-chemical descriptors like octanol/water partition coefficient (log P) representing the hydrophobicity, besides several topological and quantum-chemical descriptors particularly the energy of highest occupied molecular orbital (HOMO) [9].…”

“…This is followed by Section 3 on materials and methods, which provide information on the chemical data set and toxicity under investigation, and on the development and statistical validation of the QSAR models. The developed models are further analyzed in Section 4 on results and discussion where the internal and external predictivity of the present models is explored and compared with the robust models available in the literature [9]. Finally, the last section makes few concluding remarks.…”