Structure‐activity relationships for Pimephales and Tetrahymena: A mechanism of action approach

Abstract

The toxicity data of 74 chemicals tested in both the 96‐h fathead minnow (Pimephales promelas) mortality assay and the 2‐d Tetrahymena pyriformis (a protozoan) growth inhibition assay were evaluated using quantitative structure‐activity relationships (QSARs). Each chemical was a priori assigned a mechanism of acute toxic action from either nonpolar narcosis, polar narcosis, weak acid respiratory uncoupling, soft electrophilicity, or proelectrophilicity. The polar narcotics were further split into a phenol group and an aniline group. The relationship between bioreactivity and the importance of penetration to the site of action in both systems was studied. Bioreactivity showed a trend to be inversely proportional to the value of the hydrophobicity term. The data were examined to investigate how different molecular descriptors modeled the mechanisms of action. Models were produced for nonpolar narcotics and anilines for both species with the 1‐octanol/water partition coefficient (log Kow) alone. Soft electrophiles were best predicted by the average acceptor superdelocalizability (Snav), whereas proelectrophiles were modeled by log Kow and Snav. The weak acid uncouplers modeled with either log Kow or log Kow plus the ionization constant (pKa) for Pimephales and Tetrahymena, respectively. Phenols yielded predictive models using a either a combination of log Kow with Snav or lowest unoccupied molecular orbital, for fathead minnow and protozoan, respectively.

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

“…log K ow ) and acidity descriptor (e.g. the acid ionisation constant, pK a ) but pK a does not always appear a successful descriptor [76]. In a supervised discriminant analysis, these compounds were initially grouped together with the soft electrophiles [77] based on their E LUMO alone but the log K ow model was more similar to the one developed for polar narcosis.…”

A Machine Learning Approach to Designing Guidelines for Acute Aquatic Toxicity

“…How these properties are relevant to acute toxicity has been described previously [32,[55][56][57][58][59][60][61]. As mentioned in the introduction many of the initial classical QSAR models for acute aquatic toxicity were based on octonal-water coefficient.…”

“…For this pair of features the large differences between the LUMO and HOMO account for a chemicals non toxicity while the PSA can either be small or large. Furthermore, previous studies have shown that compounds with high octonal-water coefficient are more bioaccumulative [57,58]. The aqueous solubility and the polarity of molecule can be mechanistically related to how bioavailable the compounds will be to fish since molecules with high aqueous solubilities and high polarity will be more bioavailable to fish compared to compounds with smaller aqueous solubilities and small polarity.…”

QSAR study of the octanol/water partition coefficient of organophosphorous compounds: The hybrid GA/MLR and GA/ANN approaches

“…Repeated application leads to loss of biodiversity. 1 Many pesticides are not easily degradable, they persist in the soil, leach to groundwater and surface water and contaminate the wide environment. Depend-468 AMIRI, MESSADI and BOUAKKADIA ing on their chemical properties, they can enter the organism, bioaccumulate in food chains and consequently influence human health.…”