[The toxicological, hygienic and clinical aspects of the action of low levels of organic solvents]. / Toksikologicheskie, gigienicheskie i klinicheskie aspekty deistviia nizkikh urovnei organicheskikh rastvoritelei.

The article presents experimental data showing that Average Shift Concentration (ASC) and Maximal Single Concentration (MSC) for some solvents (tetrachloromethane, tetrachloroethane, dimethylformamide, benzene) are expedient to be justified. Clinical and hygienic materials proved significant health parameters (nervous system, peripheral blood) and urine levels of main metabolites to depend on chlorbenzene and toluene concentrations influencing the workers. Having analyzed the results, the authors recommended following hygienic norms in the air of workplace: for chlorbenzene ASC--50 mg/cu m, MSC--100 mg/cu m; biologic MAC for urine 4-chlorcatechol--0.05 g/l; for toluene ASC--50 mg/cu m, MSC--150 mg/cu m; biologic MAC for urine hippuric acid--1.5 g/l. The article shows some features of ASC and MSC practical application.

[Materials for the substantiation of the biological MAC of benzene]. / Materialy k obosnovaniiu biologicheskoi PDK benzola.

Relatively great amount of benzene-originated phenol, the presence of a definite relationship between phenol amount in the urine and benzene content in the air indicate that it is reasonable to use a phenol sample as an exposure test. To determine the intensity of benzene exposure, data on phenol content in the urine of people working at some big-tonnage enterprises has been analyzed. On the basis of the national and foreign literature data on the correlation between the phenol urine concentration and the level of benzene exposure a regression equation was deduced, which has made it possible to calculate phenol content in the urine on the level of average working day benzene concentration adopted in the USSR. This value equals 15 mg/l, which was proposed as a biological benzene MAC.

Application of toxico-kinetic criteria as a basis for toxicometric parameters.

In an experiment with single exposure to benzene and styrene at a level corresponding, to the threshold of harmful effect established by functional indices the intensity of metabolism was found to decrease. Toxico-kinetic characteristics of the substance in a single experiment permit us to prognosticate the risk of developing chronic intoxication. In comparison with indices characterizing general state of the organism, toxicokinetic indices enhance the reliability of toxicometric parameters used in determining Mac's for the air of the working area.

Results obtained in short-term experiments and their application prospects in prognosticating threshold levels of chronic exposure to chemical compounds.

Joint studies carried out by toxicologists of CMEA countries have led to the development of new ways of approach to the problem of rapid establishment of toxicometric parameters and hygienic standards (TSEL, MAC) for the working-zone atmosphere. One of the most promising approaches is the rapid establishment of MAC from the threshold of acute specific effect. Upon this principle, methodical directives for determining MAC values for specifically active irritants were elaborated. A study of the quantitative relations between toxicometric parameters and the physicochemical properties of substances in the working-zone atmosphere furnished methods for calculating TSEL values for noxious substances in this atmosphere. The essential possibility was confirmed of using isolated mitochondria as a model for preliminarily estimating the toxicity and establishing safe concentration levels of noxious substances in the working-zone atmosphere. The application of a complex of functional, biochemical and morphometric indices made it possible to foretell from short-term experiments minimal effective concentrations of a substance on chronic exposure. Ways of further research in the field of prognosticating toxicometric parameters and hygienic regulations for chemical compounds are outlined.

Intermittent exposure to toxic compounds in the working-zone atmosphere viewed from the aspect of hygienic standardization.

Four highly cumulative substances (carbon tetrachloride, 1,1,2,2-tetrachloroethane, benzene and dimethylformamide) were studied at two exposure levels under a monotonous and an intermittent exposure regimen in subacute experiments on rats. The biological effect produced by the intermittent concentrations as compared with the stable concentrations under time-weighted average concentrations depended both on the physiochemical properties and biological action of the poisons as well as on the exposure level. The intermittent concentration rises within certain limits (threefold as a rule) were injurious with some of the substances at a relatively high exposure level, but were not detrimental as compared with stable concentrations at a low exposure level. The other substances showed no difference between the effect of the monotonous and the intermittent regimens at either low or high exposure levels. The results of these studies form an experimental basis for a dual hygienic standardization: the establishment of maximum and average-shift admissible concentrations for the compounds studied as well as other highly cumulative substances.

[Comparative characteristics of 2 morphometric methods of assessing the degree of liver fatty distrophy]. / Sravnitel'naia kharakteristika dvukh morfometricheskikh metodov otsenki stepeni zhirovoi distrofii pecheni.

The fat content in the liver of white male Wistar rats was measured over time (1, 2, 4, 8 and 14 days) after a single exposure to CCl4 within a wide concentration range (from 30 to 25700 mg/m3) by the two morphometric techniques: subjective-graduation and semi-automatic evaluation of the volumetric fat fraction, using a TAS unit (Leitz-Wetzlar). The results obtained with both the methods indicate that the CCl4 concentration equal to 260 mg/m3 is the threshold one as shown by the morphological signs of liver fatty dystrophy. The semi-automatic method offered enables an objective evaluation of the findings, making the research time shorter. To obtain adequate results with the method, it is necessary to observe the rules of the morphological material treatment (contrast selective color, uniform and sufficient thickness of the sections).

Development of methodological approaches to the determination of safe levels of activity of harmful substances in the air of the working environment.

1. An experiment study was carried out to substantiate fundamental approaches to the determination of shift-average and maximum instantaneous concentration of highly cumulative substances in the air of the working environment. 2. The determination of maximum instantaneous concentrations in the air of the working environment is maintained for some groups of chemical compounds (irritant poisons, substances having acute effect, etc). An express, method of determining MAC in the air of the working environment has been developed for the purpose of hygienic norm-setting for irritant substances.