Four periods of the development of clinical toxicology in Russia can be distinguished with the help of scientifically validated criteria: the 1st (2nd half of the XIX century) – period of incipience, the 2nd (1st half of XX century) – period of formation, the third (50ties–70ties years of XX century) – period of development (formation as an independent scientific and practical direction) and the 4th (1980 –up to date) – technological (modern) period. Peculiarities of clinical toxicology as an independent scientific and practical direction of clinical medicine are: the dependence of its development on the scientific level of the basic areas of medicine; close relationship with scientific and technological achievements that have secured the development of multi-component technologies for obtaining an accurate diagnosis and controlled management of detoxification of the body and the necessity to create a specialized toxicology service operating on the basis of a relevant regulatory framework in order to implement achievements of clinical toxicology in practice. It is noted that the combination of subjective (choice of treatment methods) and objective factors (availability of material and technical capabilities) has provided the progressive development of clinical toxicology.

Keywords: history of medicine, clinical toxicology, periods of development

Toxicological and hygienic risk assessment of pesticides widespread use to human health includes the analysis of their mutagenic activity as a compulsory part. A risk assessment strategy of pesticides mutagenic impacts based on their hygiene classification by mutagenicity criterion is presented. Changes in tactical approaches having occurred recently are considered. A set of methods harmonized with international requirements for assessment of mutagenic activity of pesticides, main metabolites and components of their preparative forms is recommended. It allows to determine a hazard class by a given harmful index. Issues are considered in respect to the usage of short-time testing for assessment of generic pesticides mutagenicity, determination of preparative forms potential genotoxicity and forecasting carcinogenic properties of substances under consideration.

Keywords: pesticide, generics, mutagenic activity, assessment strategy

Lately there is an increasing interest in forensic and clinical toxicology to detect drugs and psychotropic substances in hair samples. This biological object extends opportunity to detect drugs and other toxic substances in the human body. The main difficulty in investigating the hair is a correct selection of sample preparation conditions of the object subject to chemical and toxicological studies in order to obtain a more complete extraction of toxins from the inside of the hair. For this purpose the following methods are applied: organic solvent-based extraction; organic solvent-based extraction at lower temperatures; thermal decomposition of objects; alkaline or acidic hydrolysis followed by mixed solvents-based liquid-liquid extraction; methanol-based extraction or acidified methanol-based extraction in an utrasonic bath; enzymatic hydrolysis followed by mixed solvents-based liquid-liquid extraction.

Keywords: hair, drugs, psychotropic substances, chemical and toxicological analysis, sample preparation, acid hydrolysis, enzymatic hydrolysis, barbituric acid derivatives, tropicamide

In rats with gentamicin nephropathy (gentamicin injected intra-abdominally, 60 mg/kg daily over 10 days), a combination of taurine with zinc diaspartate administrated in the stomach in the ratio of 1.0 g + 0.14g -250 mg/kg and particularly of 1.0+0.06 g - 500 mg/ kg ) has a nephroprotective effect that is proved by weakened lesions of cortical nephrons proximal convoluted tubules.

Keywords: rats, gentamicin nepthropathy, combination of taurine with zinc diaspartate, nephroprotective action

In experimental animals with 30-day and to a greater extent 60-day ethanol intoxication, the development of toxic lesion of the liver, «oxidative stress», disturbances of functional and metabolic activity of erythrocytes and neutrophils in peripheral blood was established. The application of a combination of immune modulator (longidaza), antioxidant (mexicor) and membrane protector (essentiale forte H) completely corrects metabolic disturbances at 30-day ethanol intoxication and partially at 60-day ethanol intoxication.

Keywords: ethanol intoxication, correction of metabolic disturbances

In experiments on laboratory rats and mice, features of toxic effect of a promising plant growth regulator 5-aminolevulinic acid hexyl ester (ALA-HE) were investigated under conditions of single and multiple intra gastric administration. At single intra gastric administration, a median lethal dose of ALA-HE (LD50ac ) is 3000 mg/kg for mice ( males) and 7800 mg/kg for rats ( females), specific resistivity is not expressed ( EHF<3).The threshold of acute effect Limac of 73 mg/kg was established at the level of median effective dose ED50 ( mice) . The cumulation coefficient obtained according to Lim et al method in experiments on mice makes 6.1. In experiments on rats according to Yu.S. Kagan and V.V.Stankevich method, the value of the cumulation coefficient was 1.6 at exposure to 1/5-fold of LD50. As a maximum tolerated dose, the value of 440 mg/kg ( 1/20 of LD50.) was adopted.

Keywords: aminolevulinic acid hexyl ester, toxicity, single exposure. cumulative properties

Some postulates of the theory and mathematical modeling of combined toxic effect are considered critically and their further development is suggested. To this end, results of experiments on rats exposed to repeated intraperitoneal injections of several binary and a three-factorial combination of chemicals, mostly toxic metals salts or metalcontaining nanoparticles were analyzed. Intoxications were quantitatively characterized with tens of functional, biochemical and morphometric indices. The mathematical description of combined effects was based both on common descriptive statistics and two mathematical models using analysis of variance ANOVA (a) and (b) mathematical theory of response surface construction which correlate with widely recognised paradigms of the combined toxicity theory- additivity of effects and doses additivity respectively. It was concluded that these paradigms are virtually interchangeable and should be considered as different methods of combined toxicity modelling rather than as representing fundamentally differing processes. Thus, the zero interactive response surface regression model seems preferable because it is invariant with respect to these paradigms. Within a mathematical model there exist not only three traditionally used types of combined toxicity (additivity, subadditivity and super additivity) but a lot of its variants depending on which effect is exactly considered and on its level, as well as on the dose levels and their ratio. A special attention is given to modeling opposing effects of toxics. The expedience of introducing a concept of a main (determinant) type of combined toxicity is emphasized, and criteria of its choice are proposed. For characterizing the three-factorial toxicity, a new health risk-oriented approach is suggested, the gist of which is a classification of effects depending on whether a binary combined toxicity type remains virtually the same or appears to be either more or less adverse when modeled against the background of the third toxic. The relevance of the above results to health risk analysis and management is briefly discussed.

Keywords: combined toxicity, risk analysis, isobolograms

Sensitivity of hydrobionts to PVC plasticates decreasing in the following series: infusoria Paramecium caudatum > bacterial test-system «Ecolum»> Ceriodaphnia affinis> Daphnia magna is demonstrated., It was shown on the example of Daphnia magna manifesting the highest viability that water extracts of PVC plasticates inhibit the trophic activity of crustaceans, their reproductive power and increase species mortality. It is probable that those effects are caused by the presence of phthalates in water extractions. The search for safe formulations should be directed towards finding an optimal correlation between PVC polymer, plasticizer and heat stabilizer and replacement of composition ingredients with safe substances as well.

Keywords: toxicity, bio testing, polyvinyl chloride plasticates, plasticizers, hydrobionts

The influence of different concentrations of TiO2 nano-particles water suspensions (anatase and rutile isoforms) on survival and fertility of cladocerans Ceriodaphnia affinis was investigated. A statistically significant decrease of crustaceans survival in 400 mg/l and 100 mg/l anatase water suspensions over 7 days was observed. Median life span of animals authentically differed from control values in rutile 2.00 mg/l and 0.2 mg/l suspensions and anatase in all studied concentrations. The indicator value decreased with an increasing substance concentration (r=-0.21; p < 0.02). TiO2 isoforms produced negative effect on the Ceriodaphnia reproduction function. An authentic reduction of crustaceans total fertility over life span was recorded for anatase in concentrations of 0.2 mg/l and 0.02 mg/l and rutile in concentration of 0.2 mg/l. Anatase having equal concentrations with rutile posed a more expressed toxic effect on Ceriodaphnia which is linked to its lesser particles size.

Keywords: titanium dioxide, nanoparticles, toxicity, ceriodaphnia