[Methods in the assessment of combined effect of substances].

Russian and foreign approaches to estimating the combined effect of substances are considered depending on the problems to be solved Data are given on the relationship of the type of combined effect to the mechanism of the toxic action of components and acting doses (concentrations). Various mathematical models for calculating the combined efect of mixtures are discussed There is evidence that it is necessary to study the combined effects of the mixtures of constant composition, which are used in water supply upon chronic exposure of the substances that are constituents of the mixtures. Based on their studies and the data available in the literature, the authors inferred that the nature of the combined effect of such mixtures should be investigated under the conditions suiting those of application, as well as when used at low concentrations.

[Dependence of carcinogenic properties of benzene derivatives on structure of their substituents adjusted for biotransformation].

An oxenoid model of the effect of cytochrome P450 and quantum chemical calculations were used to study a relationship of the carcinogenic activity of the benzene derivatives C6H5-X and C6H4-XY to the nature of the substituents X and Y For mono- and disubstituted benzenes, the methods based on the neglect of diatomic differential overlap was used to calculate the minimal values of AE for this compound, which is the minimum difference in the complete energies of the arenoxide intermediate OC6-H5-X or OC6H4-XY with one tetraedrically coordinated carbon atom in the benzene ring in reference to the initiar molecule of substituted benzene. The boundary value of the parameter deltaE min' which separated cancerogenic compounds from noncancerogenous ones was determined. A classification for nitrosubstituted benzenes was clarified using the parameter characterizing bioactivation via nitro group reduction to form phenylhydroxylamines and then nitrenic ions.

[Classification of substances to predict the order of magnitude of their safe water levels in terms of carcinogenic effect].

A classification has been developed to predict the safe water levels of chemical compounds in terms of their carcinogenic effect, by using as the base the LTD@10 value that is a lower 95% confidence limits for the lowest dose that statistically significantly causes a 10% increase in the incidence of cancer in laboratory animals continuously receiving a daily dose of the compound throughout their life, which is given in the CPDB internet resource, and the carcinogenicity classification adopted by the International Agency or Research on Cancer Based on an analysis ofthe maximum allowable concentration (MAC) of the standardized water substances in terms of their carcinogenic effect, the authors determined MA4 C ranges corresponding to different classes in accordance with the proposed classification. They predicted the orders of magnitude of MAC of the standardized water substances without taking into account their carcinogenic effect and those of four substances unstandardized in Russia.

[Experimental study of proflavine acetate phototransformation processes].

Changes in proflavine acetate phototransformation processes upon exposure to visible-range irradiation were studied by high performance liquid chromatography. Proflavine acetate was offered as a photosensitizer during photodynamic water disinfection. Dye transformation products upon time-varying exposure to irradiation were identified.

[General and specific aspects of the toxic properties of nanoparticles and other chemical substances in the context of classical toxicology].

The properties of nanoparticles versus chemical compounds in other physical forms were evaluated in the context of classical toxicology. A relationship of the toxicity of nanomaterials to the structure of molecules and the size of nanoparticles is discussed. Summing up the data available in the literature leads to the conclusion that there are general and specific aspects in the study of the toxicity of nanoparticles and chemical substances in other physical forms.

Directions in QSAR modeling for regulatory uses in OECD member countries, EU and in Russia.

The aim of this article is to show the main aspects of quantitative structure activity relationship (QSAR) modeling for regulatory purposes. We try to answer the question; what makes QSAR models suitable for regulatory uses. The article focuses on directions in QSAR modeling in European Union (EU) and Russia.

Regulatory assessment of chemicals within OECD member countries, EU and in Russia.

The chemical risk assessment is essesntial part of new chemical legislation registration, evaluation, and authorization of chemicals (REACH). The article presents a review of chemical legislation policies in the European Union (EU) and in Russia, and changes in chemicals regulations to meet the requirement of REACH. The risk assessment paradigm, toxicological parameters, safe limits and classification criteria used by different agencies and authorities in different countries are reported.

[Application of quantum-chemical methods to prediction of the carcinogenicity of chemical substances].

A version of logical-combinatorial JSM type intelligent system was used to predict the presence and the degree of a carcinogenic effect. This version was based on combined description of chemical substances including both structural and numeric parameters. The new version allows for the fact that the toxicity and danger caused by chemical substances often depend on their biological activation in the organism.

[A system for predicting the toxicity and hazard of chemical substances, based on the joint use of logistic and numerical methods].

A version of a logical combinatorial intellectual system (DMS system) has been developed to predict the toxicity and hazards of chemical substances. The system is based on the combined description of the substances, which includes both structural and numerical descriptors, particularly those characterizing the reactivity of compounds or their metabolites. The selection of numerical descriptors is based on the classification of processes of the interaction of the substance with the body in accordance with the key stage of the mechanism responsible for its toxic action.

[Quantum chemical model for prediction of the site of hydroxylation of aromatic substances mediated by cytochrome P450].

An approach based on the oxenoid model of monooxygenase action and semiempirical quantum chemical calculations was applied to the prediction of aromatic hydroxylation sites of cytochrome P450 substrates. The results were compared with experimental data on the metabolism in mammals and human from Metabolite database.

A new statistical approach to predicting aromatic hydroxylation sites. Comparison with model-based approaches.

A new approach is described that is able to predict the most probable metabolic sites on the basis of a statistical analysis of various metabolic transformations reported in the literature. The approach is applied to the prediction of aromatic hydroxylation sites for diverse sets of substrates. Training is performed using the aromatic hydroxylation reactions from the Metabolism database (Accelrys).

[Comparative assessment of enteral and inhaled n-butanol in laboratory animals].

Enteral and inhaled n-butanol given to albino rats was tested for toxicity in 2 series of subacute 30-day toxicological experiments. Enteral and inhalant administration caused membrano-, hepato-, adrenotoxic effects, and inhalant administration produced neurotoxic ones. The threshold dose was 0.

[Formation of organochlorine compounds in the chlorination of water containing industrial contaminants: Experimental assessment and forecasting].

The hazard of GSS production from commercial chemicals was evaluated during water chlorination by analyzing the results of experimental study of chlorination of chemicals from different classes. Structural fragments were found, their presence in the molecule determined the capacity of a substance to undergo intensive transformation to form GSS. The regularities that associates the structure of a substance with the rate of chlorination were detected.

[Bases of safe substance levels for unified sanitary standards].

The study was undertaken to detect substances whose threshold and safe levels cannot be used without their correction in order to provide unified sanitary standardization. The criteria for choosing the substances were their high stability, capacity of bioaccumulation, the presence of mutagenic and/or carcinogenic properties and great discrepancy between the values of chronic toxicity of a substance and structure-activity relationships, which are typical of the structural series it belongs to. The use of these criteria may identify 155 substances standardized in water and 126 in the ambient air, whose threshold and safe levels in their oral and inhaled administrations are to be clarified.

[Theoretical rationale for structure-genotoxicity relationships in the series of halogenated short-chain aliphatic compounds for mammals and bacteria].

Structure-genotoxicity relationships for mammals and structure-mutagenic activity relationships for bacterial were derived in the series of halogenated short-chain hydrocarbons and alcohols, by using the calculated quantum chemical parameters, namely the energy differences of frontier molecular orbitals and the electronic characteristics of the probable metabolites.