Maria Livia Tosato

A strategy for ranking environmentally occurring chemicals

A systematic methodology for quantitative structure-activity relationship (QSAR) development in environmental toxicology is provided. The methodology is summarized in a strategy with six sequential ...

Herbicidal triazines: Acute toxicity onDaphnia, fish, and plants and analysis of its relationships with structural factors

The 24- and 48-hr EC50 immobilization test of Daphnia magna has been performed on 14 herbicidal triazines characterized by structural differences with respect to the substituent groups at the three carbon atoms in the s-triazinic ring. EC50 values of the tested compounds were found to vary within a factor of 6 to 7; such variations of toxicity have been analyzed in terms of structural variations concerning (i) the type of substituents, i.e., Cl, SCH3, or OCH3, at the carbon atom C-2, and (ii) the number and size of the alkyl groups at the aminic nitrogen atoms bound to the ring carbons C-4 and C-6. Literature data relative to the acute toxicity of the considered herbicides on fish and plants were also analyzed with reference to the above structural features. The possibility that separate contributions to toxic effects of triazines are provided by specific groups bound to the common structural moiety, constituted by the 1,3,5-triazinic ring, is examined and discussed.

Approaches to modeling toxic responses of aquatic organisms to aromatic hydrocarbons

Acute toxic effects on Salmo gairdneri, Poecilia reticulata, Daphnia magna, and the growth inhibition of Selenastrum capricornutum were measured for eight aromatic hydrocarbons. Toxicity measurements were carried out following the OECD standard guidelines modified as appropriate in order to prevent hydrocarbon loss by volatilization; the concentrations of the substrates in the test solutions were periodically measured by HPLC. The toxic responses were analyzed in terms of the n-octanol/water partition coefficients, by means of linear regression analysis, and in terms of five molecular properties simultaneously, by means of the partial least squares analysis in latent variables (PLS). The univariate and multivariate quantitative structure-activity relationship models obtained by the two approaches are compared and discussed.

Comparison of the susceptibility of daphnids and fish to benzene derivatives

Abstract A battery of acute toxicity tests with a variety of aquatic organisms may represent a valid approach for preliminary hazard assessment. As the difference in sensitivity among species can be very large, it is fundamental that the test organisms are properly selected. The paper compares the sensitivity of three aquatic species — Ceriodaphnia dubia, Daphnia magna , and Pimephales promelas (fathead minnow) larvae — to acute effects of toxicants. The comparison is based on data for nine compounds; namely, benzene and eight monosubstituted benzenes (MBs) expected to span a sufficiently wide range of toxicity. The results of acute toxicity tests with Ceriodaphnia dubia and fish larvae showed that the two organisms have a very similar susceptibility towards the tested chemicals, with the major exception of aniline, which was more toxic to daphnids than to fish (the actual LC 50 s differing by more than two orders of magnitude). Toxicity data for Daphnia magna , available from a previous study, show a trend similar to that observed with Ceriodaphnia dubia , but, at the same time, suggest that this species is equally or more sensitive than Ceriodaphnia dubia and fathead minnow.

Multivariate modelling of the rate constant of the gas-phase reaction of haloalkanes with the hydroxyl radical

Abstract A QSAR strategy for screening toxic substances and identifying priorities for testing has been applied to haloalkanes with the objective of modelling their reaction rate constant with the hydroxyl radical in the gas phase, k(OH). A model has been calibrated using a training set of nine haloalkanes selected from a series of 58 by means of a statistical design. The model correlating the rate constant with 12 structural descriptors was obtained using partial least squares (PLS), and found to explain almost 90% of the variation in k(OH). Its predictive capability was tested using 16 validation compounds not included in the model calibration. The analysis indicated that several structural variables simultaneously contribute to the variation in k(OH). A simplified multivariate model based on qualitative and indicator variables has also been developed for estimating the rate constant of haloalkanes, aliphatic alcohols, ketones and aldehydes. The multi-class model was developed under the assumption of a similar mechanism of reaction with the hydroxyl radical.

Atmospheric chemistry: rate constants of the gas-phase reactions between haloalkanes of environmental interest and hydroxyl radicals

Abstract The rate constant (K OH ) of the gas-phase oxidation of hydrohalo-methanes and -ethanes by hydroxyl radical (OH) has been modelled in terms of eleven qualitative descriptors drawn from the chemical structure. The multivariate model was calibrated on a training set of 16 compounds selected by a statistical design out of the investigated range of structures. It was experimentally validated by comparing the predicted with the actual K OH .S available for 15 additional compounds. The standard deviation of the prediction errors in the reactivity range of the series (−14.77 ⩽ log(k OH ) ⩽ 12.40 in our study) was found to be ± 0.24.

A STUDY OF THE DONOR PROPERTIES OF THE CARBONYL GROUP OF PYRIDONES

Abstract The donor properties of the CO group of pyridones have been examined by studying the IR spectra of their complexes with mercury-(II)-chloride and with hydroquinone. The complexes with mercury chloride are formed by a weak O⋯Hg donor-acceptor bond, while the others have the character of strongly H-bonded salts of hydroxypyridinium cations. The dipole moment of N-methyl-3-pyridone, not reported so far, has also been measured, (7·2 D). These results, and the agreement between the theoretical and the experimental dipole moments, support the prediction that the donor properties of the CO group are very similar for the three isomers.

Application of chemometrics to the screening of hazardous chemicals A case study

Abstract Tosato, M.L., Piazza, R., Chiorboli, C., Passerini, L., Pino, A., Cruciani, G. and Clementi, S., 1992. Application of chemometrics to the screening of hazardous chemicals. A case study. Chemometrics and Intelligent Laboratory Systems , 16: 155–167. The key aspects of a priority setting process for risk assessment of chemicals are reviewed. The process is based on the assumption that chemical and biological properties can be modelled within series of closely similar compounds. It rests heavily on multivariate methodologies for the development of predictive models. Statistical design, in particular, is essential for optimizing the selection of the most informative objects and variables to be used in the calibration of the models. A case study is presented where the process is applied to all (EEC-wide) commercially available halo-methanes, -ethanes and -propanes with the objective of modelling their tropospheric reactivity and, hence, estimating their lifetimes. A training set of just nine, properly informative haloalkanes was first selected from a series of 142; their reactivity was expressed in terms of the rate constant of their reaction with the OH radical, k (OH); their structure was parametrized by a selected set of variables that, by using a new statistical method, were found to optimize the k (OH) model. The experimentally validated model provided k (OH) estimates, and hence allowed the formulation of a persistency ranking for the non-tested compounds in the series, which also included several hydro-chlorofluorocarbons, H-CFCs, presently considered as possible replacement chemicals for the extremely stable, environmentally incompatible ozone-depleting CFCs.

Updating and validation of a daphnia toxicity model for benzene derivatives

Abstract A QSAR model for predicting the acute toxicity to Daphnia of mono-substituted benzenes (MBs) has been updated and validated experimentally. The model had been previously constructed by using a training set of eight MBs, which were selected by a statistical design out of a series of 100 and subsequently tested on their toxicity. For updating the model, a recently developed data analytic method based on PLS (Partial Least Squares) has been applied. For its validation, a total number of thirteen MBs have been tested under the same conditions as used for the training set. The selection of the validation compounds was carried out with a view to identifying potential structural and mechanistic outliers. The study allowed us to clarify the range of the model and to assess the accuracy of the predictions for non-tested MBs. The agreement between actual and predicted toxicities was good for the validation compounds ( Q 2 = 0.89); it was also acceptable for other MBs whose toxicities were reported in the literature.

Quantitative Structure—Activity Relationships (QSARs): An Integrated Multivariate Approach for Risk Assessment Studies

The conditions and methods for constructing reliable QSARs are revised in relation to each component of a QSAR study: the selection of a training set out of a QSAR compatible series, the collection of data pertinent to the descriptors matrix (X) and to the effects matrix (Y), the analysis of data to connect X to Y by a regression model, and the validation of the model. In discussing these conditions, attention is given to the constraints that arise from the theoretical foundation of QSARs as analogy models of local validity and to the complexity and limited knowledge about the mechanisms of action. Hence, emphasis is placed on the need and importance to adopt multivariate methods for dealing with (1) the characterization of the structures, (2) the selection of a representative set of training compounds, and (3) analysis of the data. It is finally shown that the same integrated multivariate approach applies to the modeling of biological activities and other properties—chemical and biological—as well as to the modeling of correlations between batteries of data. The role of QSAR in risk assessment is addressed in the second part of the article. The framework of a strategy for an efficient screening assessment of toxic substances through the modeling of their exposure and toxicity-related properties is outlined. Applications of the strategy are reported that deal with two series of compounds. Examples of toxicity and persistency models are illustrated.