[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.

[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.

[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.

[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. By using structure-activity relationships and information from toxicity databases, the authors evaluated the hazard of the identified products and identified the most hazardous ones.

[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. There is a relationship of their toxicity to the dose and time of exposure for both nanoparticles and other chemical substances. It is noted that, as in classical toxicology, main conclusions on the toxicity and hazard of nanoparticles can be drawn only from traditional chronic toxicological experiments on the adequate route of their entry into the body.

[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. The authors substantiate classifying chemicals according to their carcinogenic activity, and illustrate the use of the system to predict the carcinogenicity of polycyclic aromatic hydrocarbons using a model of bioactivation via the formation of diolepoxides, and the carcinogenicity of halogenated alkanes using a model of bioactivation via oxidative dehalogenation. The paper defined the boundary level of an energetic parameter, the exceeding of which correlated with the inhibition of halogenated alkanes's metabolism and the absence of carcinogenic activity.

[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 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. The new version of the DSM system takes into account the fact that the toxicity and hazard of chemicals are frequently determined by their bioactivation. Examples of how to apply the system to the prediction of carcinogenicity are given.

[Comparative assessment of enteral and inhaled n-butanol in laboratory animals]. / Sravnitel'naia otsenka toksichnosti n-butanola pri énteral'nom i ingaliatsionnom postuplenii v organizm laboratornykh zhivotnykh.

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 0.2 mg/kg, the maximum ineffective one was 0.04 mg/kg. The threshold concentration was not established in the experiment. The less than 95% confidence limits of reference points (BMDL and BMCL), which cause a 10%-increase in the frequency of adverse reactions (blood catalase induction), were 0.052 mg/kg with enteral administration and 0.18 mg/m3 (0.076 mg/kg) on inhalation. The comparative toxicity coefficient (BMDLent/BMDLinh = 0.68) for n-butanol suggests that there is no difference in toxicity on different routes of administration.

[Formation of organochlorine compounds in the chlorination of water containing industrial contaminants: Experimental assessment and forecasting]. / Eksperimental'naia otsenka i prognoz obrazovaniia khlororganicheskikh soedinenii pri khlorirovanii vody, soderzhashchei promyshlennye zagriazneniia.

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. Some theoretical approaches to the determination of the ability of chemical to chlorinate are outlined.

[Bases of safe substance levels for unified sanitary standards]. / O obosnovaniiu bezvrednykh urovnei dlia edinogo gigienicheskogo normirovaniia veshchestv.

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]. / Teoreticheskoe obosnovanie sviazi struktura-genotoksichnost' dlia mlekopitaiushchikh i bakterií v riadu galogenozameshchennykh alifaticheskikh soedinenií s korotkoí tsep'iu.

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.