Showing papers in "Sar and Qsar in Environmental Research in 1997"
TL;DR: In this article, a set of 40 simple heterogeneous compounds is used to show the main characteristics, some properties and the modelling power of WHIM descriptors by using simple scatter plots of the descriptors.
Abstract: WHIM descriptors are 3-dimensional molecular indices that represent different sources of chemical information. WHIM descriptors contain information about the whole 3D-molecular structure in terms of size, shape, symmetry and atom distribution. These indices are calculated from (x, y, z)-coordinates of a molecule within different weighting schemes in a straightforward manner and represent a very general approach to describe molecules in a unitary conceptual framework. A set of 40 simple heterogeneous compounds is used to show the main characteristics, some properties and the modelling power of WHIM descriptors by using simple scatter plots of the descriptors. These descriptors have been used to search for quantitative structure-activity and structure-property relationships for several classes of environmental relevant compounds. Comparisons with other sets of descriptors have also been performed.
82 citations
TL;DR: The results show that the hierarchical QSAR approach using the algorithmically derived molecular descriptors can estimate the LC50 values of the benzene derivatives reasonably well.
Abstract: Four classes of theoretical structural parameters, viz., topostructural, topochemical, geometrical and quantum chemical descriptors, have been used in the development of quantitative structure-activity relationship (QSAR) models for a set of sixty-nine benzene derivatives. None of the individual classes of parameters was very effective in predicting toxicity. A hierarchical approach was followed in using a combination of the four classes of indices in QSAR model development. The results show that the hierarchical QSAR approach using the algorithmically derived molecular descriptors can estimate the LC50 values of the benzene derivatives reasonably well.
57 citations
TL;DR: A number of structure-odor relationships concerning odor intensity and odor quality are presented and an attempt was made to recognize principal trends in the field of structure -odor relationships.
Abstract: A number of structure-odor relationships concerning odor intensity and odor quality are presented. The sets which were used, the statistical methods which were employed and the principal results of the studies are analyzed and discussed. An attempt was made to recognize principal trends in the field of structure-odor relationships.
51 citations
TL;DR: In this paper, two new molecular complexity measures, namely topological complexities (TC) and zero-order complexity (ZOC), are introduced, based on the idea that topological complexity increases with the overall connectivity of the molecular graph.
Abstract: The development of molecular complexity measures is reviewed. Two novel sets of indices termed topological complexities are introduced proceeding from the idea that topological complexity increases with the overall connectivity of the molecular graph. The latter is assessed as the connectivity of all connected subgraphs in the molecular graph, including the graph itself. First-order, second-order, third-order, etc., topological complexities i TC are defined as the sum of the vertex degrees in the connected subgraphs with one, two, three, etc., edges, respectively. Zero-order complexity is also specified for the simplest subgraphs–the graph vertices. The overall topological complexity TC is then defined as the sum of the complexities of all orders. These new indices mirror the increase in complexity with the increase in the number of atoms and, at a constant number of atoms, with the increase in molecular branching and cyclicity. Topological complexities compare favorably to molecular connectiviti...
43 citations
TL;DR: Structural, topological, and 3D-WHIM descriptors are used for modelling toxicological and physico-chemical properties of compounds that are included in the European Union's so-called "List 1" of priority chemicals dangerous for the aquatic environment.
Abstract: In environmental and ecotoxicological problems, the need for more general predictive models is one of the aims of the science. To reach this objective, the models, even if capable of producing more approximate values, must be applicable to the huge number of chemicals put on the market that are discharged in the environment, at least for setting priority lists among potentially hazardous substances. Theoretically, the problem is not insurmountable if one assumes that all properties of a chemical (physico-chemical, biological, toxicological) are related to its structural features. The challenge is to describe and represent, on a quantitative basis, all molecular structural features in order to use them as independent variables in a quantitative structure-activity model. In this paper, structural, topological, and 3D-WHIM descriptors are used for modelling toxicological and physico-chemical properties of compounds that are included in the European Union's so-called “List I” of priority chemicals da...
39 citations
TL;DR: The characterization of molecular structure using structural invariants has increased greatly over the last ten years as mentioned in this paper, and topological indices have become more widely used in the quantification of molecular structures for use in quantitative structure-activity relationship studies, chemical documentation, and molecular similarity studies.
Abstract: The characterization of molecular structure using structural invariants has increased greatly over the last ten years. Specifically, topological indices have become more widely used in the quantification of molecular structure for use in quantitative structure-activity relationship studies, chemical documentation, and molecular similarity studies. The basis, calculation, and utility of topological indices has been examined, with an eye to the specific advantages and problems in their use. In addition, variable clustering and principal component analysis are examinee as two potential solutions to the problem of index intercorrelation.
37 citations
TL;DR: A backpropagation neural network model, implemented in AUTOLOGP (Version 40), was developed for estimating the n-octanol/water partition coefficient of organic molecules from their structure described by means of a modified autocorrelation method as mentioned in this paper.
Abstract: A backpropagation neural network model, implemented in AUTOLOGP (Version 40), was developed for estimating the n-octanol/water partition coefficient of organic molecules from their structure described by means of a modified autocorrelation method The advantages of the autocorrelation method, which allows the description of any kind of molecules by means of computerized molecular descriptors presenting a physicochemical meaning, were emphasized through the simulation performances obtained with AUTOLOGP (Version 40) and from a comparative study involving two regression models derived from various topological indices
28 citations
TL;DR: In this paper, four graph operators are used to compute 19 topological indices for a set of 306 alkanes and the intercorrelation coefficients of these indices are computed and used to identify highly intercorrelated indices.
Abstract: A number of recently graph matrices encoding in various ways the topological information is presented. Four graph operators are used to compute 19 topological indices for a set of 306 alkanes. The intercorrelation coefficients of the 19 topological indices are computed and used to identify highly intercorrelated indices.
25 citations
TL;DR: An efficient algorithm for deriving QSPR/QSAR models with non-orthogonal and ordered descriptors, based on orthogonalization of topological indices, is presented in this article.
Abstract: An efficient algorithm for deriving QSPR/QSAR models with nonorthogonal and ordered orthogonal descriptors, based on orthogonalization of topological indices, is presented. It is applied to structure-boiling point modeling of nonanes as the test case. The selection of the best descriptors from multivariate linear regression modeling is carried out using descriptors which are first orthogonalized. It is shown that such an algorithm is applicable for the selection of the best descriptors in a multivariate linear regression model even to very large sets of descriptors. A computationally-effective method for the (ordered) orthogonalization of topological indices is also introduced. By the use of an ordered orthogonalization procedure it is possible to select the best order of descriptors for orthogonalization. The orthogonalization in the selected order of descriptors produces models with a smaller number of significant descriptors. The comparison between QSPR/QSAR models with nonorthogonal and order...
22 citations
TL;DR: CBR QSARs may not be applicable to very hydrophobic chemicals, chemicals with specific modes of action, or those with toxicity controlled by kinetic processes such as biotransformation, and may be affected by genetic, hormonal or environmental variation.
Abstract: The critical body residue (CBR) is the concentration of chemical bioaccumulated in an aquatic organism that corresponds to a defined measure of toxicity (e.g., mortality). The CBR can provide an alternative measure of toxicity to traditional waterborne concentration measurements (e.g., concentration in water causing 50% mortality). The CBR has been suggested as a better estimator of dose than the external water concentration and has been postulated to be constant for chemicals with the same mode of action. CBR QSARs have both theoretical and experimental support, developed primarily from studies on the acute toxicity of narcotic chemicals to small fish. CBR QSARs are less well developed for the aquatic toxicity of non-narcotic chemicals. CBRs vary substantially with the mode of action and toxicity endpoint, and may be affected by genetic, hormonal or environmental variation. CBR QSARs may not be applicable to very hydrophobic chemicals, chemicals with specific modes of action, or those with toxicity controlled by kinetic processes such as biotransformation. CBRs models have not been developed or evaluated for sediment and dietary exposure routes. Application of CBR QSARs to contaminated site assessments will require further research and development.
18 citations
TL;DR: In this paper, the authors used the fragmental/regression model of Klopman and co-workers and the autocorrelation/backpropagation neural network model implemented in AUTOLOGPTM (Version 4.0).
Abstract: The values of log P (n-octanol/water partition coefficient) for 1449 chemicals were calculated from the fragmental/regression model of Klopman and co-workers (J. Chem. Inf. Comput. Sci. 1994, 34, 752-781) and from the autocorrelation/backpropagation neural network model implemented in AUTOLOGPTM (Version 4.0). Both models provided good simulation results but the superiority of the latter was demonstrated.
TL;DR: Two new physiologically-based pharmacokinetic (PBPK) models are developed which predict the concentration of Dibromomethane in the blood of rats after dermal vapor exposure and could be a great improvement over previous models in the ability to extrapolate results for different species, doses, and durations.
Abstract: Understanding the absorption of chemicals through the skin is of importance to many fields of study. Biologically-based models can be used to simulate the absorption process and predict the rate of absorption and the amount of the chemical in various parts of the body and skin. When these models consist of physiological and biochemical parameters that can be measured, they can be extremely useful. When a model is appropriately validated, the results can be extrapolated across species to predict the effect of human exposure. In this paper we develop two new physiologically-based pharmacokinetic (PBPK) models which predict the concentration of Dibromomethane in the blood of rats after dermal vapor exposure. These two new models expand a previously developed homogeneous skin model by adding parallel skin subcompartments to represent skin appendages and layered subcompartments to represent the distinct layers of the skin. The predictions of these new models match the experimental data better than the...
TL;DR: In this paper, two sets of molecular indices have been employed for modelling: Topological Indices (TIs) and Weighted Holistic Invariant Molecular (WHIM) descriptors.
Abstract: Quantitative Structure-Activity Relationships (QSAR) studies are powerful tools to rationalize complex systems where physico-chemical properties and biological activities of compounds of environmental and toxicological interest are involved. In these fields, due to costs, time, and difficulties in obtaining experimental measures, one of the main objectives is to fill the need for general predictive models. The challenge is to describe and represent, on a quantitative basis, all the molecular structural features in order to use them as descriptors in quantitative structure-activity models. In this study, two different sets of molecular indices have been employed for modelling: Topological Indices (TIs) and Weighted Holistic Invariant Molecular (WHIM) descriptors. In particular, the recently proposed WHIM indices, containing complete 3D information on molecular size, shape, symmetry and atom distribution, have already been successfully used in modelling physico-chemical properties and biological ac...
TL;DR: To describe the role of each of the descriptors, a new method was suggested based upon the estimation of the connection weights, the identification and the rationalisation of the residuals, which proved to give better results than a regression analysis technique and the most accurate predictions.
Abstract: Structure-toxicity relationships for 120 insecticidal DDT-type molecules including diaryl nitropropanes (Prolan analogs), diaryl trichloroethane and other DDT isosters, collected from different literature sources, to Musca domestica, were analysed by regression analysis (RA) and a neural network model (NN). The steric factors are extremely important to the toxicity of all the DDT-type analogs. The lipophilicity is also important for the groups, because it facilitates delivery of these neurotoxicants to the site of action in the nerve. On the basis of training results, the NNs proved to give better results than a regression analysis technique and the most accurate predictions. To describe the role of each of the descriptors we suggested a new method based upon the estimation of the connection weights, the identification and the rationalisation of the residuals.
TL;DR: A plausible mechanism for the mutagenic activity of halogenated furanones (so called MX compounds) in Salmonella typhimurium TA100 tester strain is proposed and it seems reasonable to suggest that the Mutagenicity of these direct-acting compounds may be a purely thermodynamic phenomenon, rather than the result of site-specific binding or adduct formation.
Abstract: Combining our previous QSAR work with recent high-level quantum mechanical calculations, a plausible mechanism for the mutagenic activity of halogenated furanones (so called MX compounds) in Salmonella typhimurium TA100 tester strain is proposed. The mechanism involves one-electron reduction as a key step and it seems reasonable to suggest that the mutagenicity of these direct-acting compounds may be a purely thermodynamic phenomenon, rather than the result of site-specific binding or adduct formation. Overall, the proposed model is consistent with the most experimental findings.
TL;DR: In this article, the normal boiling point was modeled for a set of 372 saturated compounds, including 154 alkanes, 108 alcohols and 110 (poly)chloroalkanes, using artificial neural networks with back propagation of error.
Abstract: The normal boiling point is modeled for a set of 372 saturated compounds, including 154 alkanes, 108 alcohols and 110 (poly)chloroalkanes. The newly introduced atom type electrotopological state indices serve as the structure variables and artificial neural networks (with back propagation of error) are used for the analysis. A network with a 6:7:1 architecture produces an average relative error of 0.97% for the whole data set, including the 21% of the data used as the test set. The mean absolute error (MAE) for this model is 4.00 for the whole set, corresponding to an rms error of 5.41; for the test set the MAE is 4.03 with an rms of 5.23. The low error on the test set indicates that this model has predictive power.
TL;DR: A review of factors that have combined to create an incentive for the applying of mass balance modelling concepts to elucidating the sources, fate, and effects of contaminants in the environment is presented in this article.
Abstract: A review is presented of factors which have combined to create an incentive for the applying of mass balance modelling concepts to elucidating the sources, fate, and effects of contaminants in the environment. These factors include increased understanding of environmental processes, availability of better data on contaminant properties and toxicology, changes in regulatory approaches, growth in computing power, and the demand for comprehensive education on environmental issues. It is suggested that a set of compatible models may be emerging which treat QSARs and QSPRs; far-field, regional and global processes; near-field or local processes including bioaccumulation; and finally human exposure. Recommendations are made for actions which will enhance the use of mass balance models as an integral part of increasing our scientific understanding of chemical behaviour in the environment and especially contributing to improved chemical stewardship in the environment.
TL;DR: A validation exercise performed from eight practical case studies on EASE (version 2.0), a knowledge-based system allowing to estimate the workplace exposure to chemicals, shows that EASE represents a valuable simulation tool in occupational hygiene.
Abstract: This article presents a validation exercise performed from eight practical case studies on EASE (version 2.0), a knowledge-based system allowing to estimate the workplace exposure to chemicals. Our results show that EASE represents a valuable simulation tool in occupational hygiene. However, it requires to be refined and extended to more realistic and precise situations to be easily used in practice.
TL;DR: This study shows that a direct relation exists between one of the two components for the calculation of free energy (G degree CDS) in water and n-hexadecane, and the ecotoxicity values for five biological systems.
Abstract: Free energies of solvation of chlorophenols were calculated in two solvents: water and n-hexadecane from the AMSOL program. These free energies of solvation are the sum of two terms: polarization free energies (ΔG ENP) and cavity, dispersion, solvent structure free energies (G° CDS). This study shows, in the case of chlorophenols, that a direct relation exists between one of the two components for the calculation of free energy (G°CDS) in water and in n-hexadecane, and the ecotoxicity values for five biological systems. We point out the interest of using these new descriptors in QSAR study.
TL;DR: The aim of this study is to show that CHEMFRANCE provides valuable simulation results for understanding the environmental fate behavior of atrazine.
Abstract: Mathematical simulation models of fate and transport of chemicals have been identified by researchers and regulators as potentially valuable tools for improving the understanding of the environmental behavior of chemicals which may be released to the environment as a consequence of routine (i.e., normal manufacturing, use, disposal) and non-routine (e.g., accidental spillage) events. In this context, CHEMFRANCE, a regional fugacity model level III, which calculates the environmental distribution of organic chemicals in 12 defined regions of France, or France as a whole, has been designed. The aim of this study is to show that CHEMFRANCE provides valuable simulation results for understanding the environmental fate behavior of atrazine.
TL;DR: In this article, the relationship between structure and green or bell-pepper or nutty odours was established for a set of 88 pyrazines and 32 thiazoles by means of backpropagation neural networks (BNN).
Abstract: Relationships between structure and green or bell-pepper or nutty odours were established for a set of 88 pyrazines and 32 thiazoles by means of backpropagation neural networks (BNN). Each molecule was described by six steric hindrance or electronegativity descriptors. Excellent classification rates were obtained for the green note (97.7%, much better than the 67% obtained by discriminant analysis) and for the nutty note (96.6%). Correct prediction rates of 97.9% and 96.6% were obtained for the green and nutty notes respectively. A further test on 32 thiazoles gave a correct prediction rate of 87.5% for the bell-pepper note, and 81 3% for the green note. In another part of this study, based on similarity calculations, bell-pepper, green and nutty notes were again considered on the same compounds. First, Euclidean distances were calculated for all pairs of pyrazines, using the same descriptors as with BNN. A pyrazine possessing a given odour was considered as correctly classified if two or more of...
TL;DR: The GEOTOX estimations were in good agreement with measured values, with the ingestion pathway was the main absorption route for adults, with vegetables and fruits contributing almost 80% of the dietary intake of Mn.
Abstract: Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic derivative of manganese (Mn) used as an additive in unleaded gasoline. The combustion of MMT leads to the formation of oxides of manganese. The objective of the present study is to predict the environmental levels of Mn and the human exposure in the St-Lawrence ecozone (fluvial section, Quebec, Canada) using an environmental fate/exposure model: GEOTOX. The results of our MMT research program on abiotic and biotic components of the ecosystem and on the human exposure were used to validate the model estimations. Air and surface soil were selected as source terms with an annual Mn input rate in each compartment of 0.083-0.113 mol km-2 d-1 and 0.44-0.87 mol km-2 d-1 respectively (Mn3O4 equivalent). The predicted air, soil, plant, surface water and sediment concentrations were similar (+/- 50%) to values measured in the Montreal region. As expected, the ingestion pathway was the main absorption route for adults (> 99%), with vegetables and fruits contributing almost 80% of the dietary intake of Mn. The multimedia exposure doses for adult men predicted by the model ranged between 0.04 and 0.08 mg kg-1 d-1 compared to 0.004 and 0.201 mg kg-1 d-1 (average = 0.05) for workers from the MMT study. Considering the landscape configuration and the source vectors (air and soil) included in the model, GEOTOX estimations were in good agreement with measured values.
TL;DR: The sensitivity analysis showed that the half-life of benzo[a]pyrene in the root-zone soil is the most sensitive parameter and that it contributes significantly to the variability of the cancer risk estimation.
Abstract: This paper presents the results of a risk assessment study made using CalTOX, a multimedia, multiple pathway risk assessment model. The case study is based on the Polycyclic Aromatic Hydrocarbon (PAH) soil contamination resulting from the activities of a natural gas power station over a period of 70 years. It describes model characteristics and input parameters such as physico-chemical properties, landscape description, and human exposure factors. Model simulations and risk estimations corresponding to different remedial scenarios in an industrial zone are also presented. These estimations were based on soil contamination by 16 PAHs in the root-zone and vadose-zone layer. Results show that adult exposure (workers) to contaminated soil will lead to a potential health risk of carcinogenic effects, and to no potential risk of non-carcinogenic effects. On the other hand, the addition of 10 cm of clean soil over the contaminated soil (mitigated scenario) decreases the lifetime cancer risk to an accept...
TL;DR: In this article, molecular volumes of tetrachlorobenzyltoluenes were multilinearly regressed from their descriptors molecular volumes (V) and globularity factor (G).
Abstract: Molar volumes (v) of tetrachlorobenzyltoluenes were multilinearly regressed from their descriptors molecular volumes (V) and globularity factor (G). Regression parameters were derived from experimental liquid densities of 28 structurally related benzene- and biphenyl derivatives. The QSAR equation v = 36.1579 (±4.0228) + 0.92978(±0.1100)V+ 1.2656(±0.2685)V(1–G)(n= 28; radj 2= 0.9975; s= 1.48; F = 5313.5) appeared to be a good predictor of molar volumes. The predicted molar volumes of tetrachlorobenzyltoluenes ranged within 236.63 and 241.84 cm3·mol−1, whereas the experimental molar volume of the technical mixture Ugilec 141 was 229.78 cm3-mol−1. In general, the isomer-specific molar volumes predicted by the multilinear regression appeared to be physically more realistic compared with the molar volume obtained by the non isomer-specific additive fragment method of LeBas.
TL;DR: In this paper, a comparison of five different multi-media models (i.e., HAZCHEM, CHEMCAN, CALTOX, SIMPLEBOX, USES) was conducted.
Abstract: Although multi-media models are based on the same principle of mass balance, different assumptions may be invoked in the model construct that ultimately can lead to inconsistencies in international fate/exposure assessments. To determine the precision of five different models (i.e., HAZCHEM, CHEMCAN, CALTOX, SIMPLEBOX, USES), a comparison exercise was conducted. Calculations were performed for a set of five disparate nonpolar organic chemicals (benzene, methyl tertiary butyl ether, isopropanol, diethylhexyl phthalate and benzo[a]pyrene), with each model using the same set of inputs to define a ‘unit world’ environment and a chemical-specific emission scenario. Resulting steady-state predicted' environmental concentrations (PECs) in primary (air, water, soil, sediment) and secondary (plants, fish, meat) compartments were analyzed to assess inter-model precision. The precision of estimated residence and persistence times for each chemical was also examined. Results indicated primary compartment PEC...
TL;DR: In this paper, the authors proposed several mathematical models to estimate the environmental concentration of a chemical substance, as required by the legislation of the European Union in the context of the risk assessment of chemical substances.
Abstract: To estimate the environmental concentration of a chemical substance, as required by the legislation of the European Union in the context of the risk assessment of chemical substances, several mathematical models are proposed. Representative and reliable analytical monitoring data for the different environmental compartments are indeed only seldom available. The proposed models are simple models as for instance multimedia fugacity models. Although the results of these models only provide an imperfect approximation of the concentration in the different compartments, very high uncertainties can lie upon certain input parameters, like the quantities of the substance released during one of its life-stages, its biodegradation rate in the respective compartments or its partition coefficients between those compartments. The improvement of the risk assessment scheme as proposed by the EU-Member States should focus on these input parameters. This might imply further adapting the test methods or even the re...