Eñaut Urrestarazu Ramos

Classifying environmental pollutants. 2: Separation of class 1 (baseline toxicity) and class 2 (‘polar narcosis’) type compounds based on chemical descriptors

A large part of the xenobiotics that are encountered as aquatic pollutants can be regarded as belonging to the so‐called class 1 or baseline toxicity compounds. It is generally accepted that these compounds act through or can be considered to act through one and the same mechanism. A second important class of aquatic pollutants is formed by the slightly more toxic class 2 or polar narcosis compounds; this class of compounds is made up of, among others, phenols, anilines and similar slightly polar species and can also be considered to act through a single toxic mechanism.

Quantitative Structure−Activity Relationships for the Aquatic Toxicity of Polar and Nonpolar Narcotic Pollutants

QSARs were developed for the acute toxicity of narcotic pollutants (nonpolar and polar) to the water flea (Daphnia magna), the guppy (Poecilia reticulata), and the pond snail (Lymnaea stagnalis) using hydrophobicity (log KOW) and hydrogen bonding capacity descriptors (Q-, Q+, eHOMO, eLUMO). Toxicity increases with increasing hydrophobicity and to a minor extent with decreasing LUMO energies and increasing absolute charges in the molecule. The models are rationalized by taking into account the composition of biomembranes, into which chemicals must partition for displaying narcosis. The similarity of these results with models for the membrane/water partition coefficients supports the hypothesis that the toxicity of narcotics is directly related to the accumulation in biological membranes. The results indicate that baseline toxicity based on log KOW should be redefined for chemicals for which log KOW is not a good surrogate for partitioning into biological membranes.

Acute toxicity of polar narcotics to three aquatic species (Daphnia magna, poecilia reticulata and Lymnaea stagnalis) and its relation to hydrophobicity

Abstract The acute toxicity of a set of 11 polar narcotics was tested to the water flea, the guppy and the pond snail. As expected, the toxicity of these chemicals is higher than predicted from their respective baseline QSARs. Except for some ‘oudiers’ (anilines to the water flea), the toxicity is related to hydrophobicity. In addition, the LBB s (lethal body burdens) of these compounds were determined for the fish and the snail. Obtained LBB s for the fish are consistent with previously reported ranges for this class of pollutants. For both species, systematically lower LBB values have been found at lower exposure concentrations. Based on LB B and 96h- LC50 , bioconcentration factors ( BCF ) were calculated for the fish and the snail. Our estimates are in good agreement with measured and reported BCF s.

Algal growth inhibition of Chlorella pyrenoidosa by polar narcotic pollutants: toxic cell concentrations and QSAR modeling

Abstract The effects of 11 polar narcotic pollutants (phenols, nitrobenzenes and anilines) on the algae Chlorella pyrenoidosa have been investigated in 72 h population growth inhibition tests. The lowest observed effect concentration and no-observed effect concentrations were determined. The partial effect concentrations were estimated (EC 1 0 and EC 5 0 ) by the Weibull function, and no-effect concentrations were determined by using the debtox program. In addition, for four of the chemicals, the internal cell concentrations yielding 10 and 50% growth inhibition were estimated from internal concentration–response curves. The toxic cell concentrations vary from 0.1 to 1.6 and from 0.5 to 17 mmol kg −1 , for 10 and 50% inhibition, respectively. These values are in agreement with reported data for Selenastrum capricornutum (0.7–2.3 and 2–14 mmol kg −1 , respectively). Finally, the determined (no-)effect concentrations have been used to construct quantitative structure–activity relationship models using hydrophobicity and hydrogen bonding capacity descriptors. The models indicate that toxicity increases with hydrophobicity, good hydrogen bonding donor capacity, and low hydrogen bonding acceptor capacity. The models can be interpreted based on the composition of biomembranes, which are supposed to be the target of narcotic pollutants.

Polar narcosis: Designing a suitable training set for QSAR studies

Substituted phenols, anilines, pyridines and mononitrobenzenes can be classified as polar narcotics. These chemicals differ from non-polar narcotic compounds not only in their toxic potency (normalized by log Kow), but also in their Fish Acute Toxicity Syndrome profiles, together suggesting a different mode of action.For 97 polar narcotics, which are not ionized under physiological conditions, 11 physico-chemical and quantum-chemical descriptors were calculated. Using principal component analysis, 91 % of the total variance in this descriptor space could be explained by three principal components which were subsequently used as factors in a statistical design. Eleven compounds were selected based on a two-level full factorial design including three compounds near the center of the chemical domain (a 23+3 design).QSARs were developed for both the design set and the whole set of 63 polar narcotics for which guppy and/or fathead minnow data were available in the literature. Both QSARs, based on partial least squares regression (3 latent variables), resulted in good models (R2=0.96 and Q2=0.82; R2=0.86 and Q2=0.83 respectively) and provided similar pseudo-regression coefficients. In addition, the model based on the design chemicals was able to predict the toxicity of the 63 compounds (R2 =0.85).Models show that acute fish toxicity is determined by hydrophobicity, HOMO-LUMO energy gap and hydrogen-bond acceptor capacity.