[The main hygienic aspects of biotechnological processes]. / Osnovnye gigienicheskie aspekty biotekhnologicheskikh protsessov.

It was shown that the present technologies and implementation at the majority of biotechnological plants do not completely meet the hygienic requirements. Under such conditions, there is a complex of unfavourable factors which can have a negative effect on the production areas and environment and consequently on the workers and nearby population. The biological and, at some plants, chemical factors are the leading in the complex. The main aspects of the studies aimed at increasing the safety of biotechnological production, improving the labor conditions and decreasing the disease incidence in the personnel are described in general.

[Current problems of work hygiene in the production of semisynthetic penicillins]. / Aktual'nye voprosy gigieny truda v proizvodstve polusinteticheskikh penitsillinov.

The hygienic pattern of the technological process for production of semisynthetic penicillins is described. It is shown that the chemical factor is the leading one of the environment in manufacture of semisynthetic penicillins unlike production of natural antibiotics. The characteristics of the chemical factor by the conditions of its creation, physicochemical properties and effect on man is presented. A set of hygienic recommendations for safe performance of the technological process for production of semisynthetic penicillins was developed and is now being introduced.

[Prediction of dysbiotic effect in toxico-hygienic assessment of antibiotics]. / O prognozirovanii disbioticheskogo éffekta pri toksiko- gigienicheskoi otsenke antibiotikov.

The results of the studies showed that there was relation between the changes in the size of the typhlon and the composition of the microflora of its contents under antibiotic effect. On the basis of the analysis of the literature data and the experimental results a new toxicometric index i. e. a typhlon weight coefficient was proposed. A procedure for probabilistic estimation of the index is described. Close coincidence of the values of the threshold concentrations determined by the typhlon weight coefficient and the bacteriological methods was observed.

[Substantiation of hygienic standard of lincomycin in the air of the work area]. / Obosnovanie gigienicheskogo standarta linkomitsina v vozdukhe rabochei zony.

The main parameters of lincomycin toxicometry were studied in animals. It was shown that the compound was low toxic after its oral or intraperitoneal administration in single doses, had no local irritant and skin resorptive effects and did not accumulate. The allergenic properties were slightly pronounced. The intoxication picture after a single inhalation was characterized by renal dysfunction, erythropenia, neutrophilia, lymphopenia and impairment of the normal intestinal microflora. The zone of the specific antimicrobial effect was equal to 8. On chronic inhalation, the signs of the specific antimicrobial effect were of the paramount importance: Limch am was equal to 4.7 mg/m3 and Limch exceeded 18.3 mg/m3. In the concentrations used, the substance had no embryotoxic and gonadotropic effects. The level of 0.5 mg/m3 (for Hazard Class 2) was recommended and approved as the maximum allowable concentration.

[Comparative study of rifampicin distribution in the body of pregnant and nonpregnant white rats exposed to the antibiotic by inhalation]. / Sravnitel'noe izuchenie raspredeleniia rifampitsina v organizme beremennykh i neberemennykh belykh krys pri ingaliatsionnom vvedenii antibiotika.

When rifampicin was administered to albino rats in the form of inhalations, it was absorbed by the blood and penetrated into various organs, the levels of the antibiotic in the biosubstrates being dependent on its concentration in the inhalation air. Rifampicin distribution in the gravid animals was mainly of the same character as that in the nongravid rats. However, when the animals were exposed to the antibiotic effect during the whole period of the gravidity, a significant increase in the antibiotic levels in the blood and internal organs was observed.

[State of certain indices of natural, nonspecific immunity in workers engaged in the manufacture of neomycin and monomycin]. / Sostoianie nekotorykh pokazatelei estestvennogo nespetsificheskogo immuniteta u rabochikh, zaniatykh na proizvodstve neomitsina i monomitsina

Women occupied at various stages of neomycin and monomycin production were examined immunologically. The examination revealed insignificant changes in the phagocytic activity of the blood neutrophils, however no relation between the changes level and the level of contact with the antibiotics was observed. Changes in composition of the microflora in the deep skin layers in direction of an increase in the number of pathogenic microbes and a decrease in the bactericidal function of the skin were found in the women occupied at the final stages of the technological process, i.e. drying, packing and control.

[Placental permeability for rifampicin]. / O pronitsaemosti platsenty dlia rifampitsina.

Albino rats were exposed to rifampicin inhalations for a prolonged period of time (during gravidity). It was found that the antibiotic penetrated through the placental barrier and its levels in the fetus were proportional to its content in the air inhaled. At later gravidity periods rafampicin absorption in albino rats increased and in parallel its levels in the ovum also increased. The exposure of albino rats to rifampicin inhalations during the whole period of their gravidity in concentrations lower than the Limac (the limit of the acute effect with respect to the general toxic parameters) did not affect the structure of the placenta and its permeability by the antibiotic.

[Acute toxicity and the cumulative properties of carfecillin]. / Ostraia toksichnost' i kumuliativnye svoistva karfetsillina.

Acute toxicity of oral and intraperitoneal carfecillin was studied on different species of laboratory animals, such as albino mice, rats and guinea pigs. The average lethal doses equal to 3040 (2393.7-3860.8) and 1325 (1104.2-1590) mg/kg for oral and intraperitoneal administration respectively allowed the authors to consider the antibiotic as a low toxic substance under conditions of a single administration. Higher toxicity of carfecillin as compared to carbenicillin may be due to production of free phenol on carfecillin hydrolysin in the animal organism. The different laboratory animals of both sexes had almost the same sensitivity to the antibiotic. On repeated administration of carfecillin to the albino mouse stomach (in portions of LD50) no cumulative properties of the antibiotic were observed.

[Evaluation of the antimicrobial action of substances for the setting of hygienic standards]. / Otsenka antimikrobnogo deistviia veshchestv s tsel'iu gigienicheskogo normirovaniia.

The notion of antimicrobial effect threshold as an index of hygienic importance for toxicological estimation of chemotherapeutic agents is grounded by the generally accepted conception of thresholds of substances harmful effect. The methodical means used in determining the antimicrobial effect threshold including the recommended set of the measurable indices of intestinal microflora are discussed.

[Problems of the hygienic standardization of antibiotics]. / Problemy gigienicheskogo normirovaniia antibiotikov.

Some of the results of the development of hygienic standardization of antibiotics are discussed. The main scheme proposed earlier was tested in hygienic investigation of antibiotics of various groups. Separate elements of the scheme were shown to be reliable and approaches to its further improvement were suggested. The trends of promising studies on toxicology of antibiotics aimed at their hygienic standardization are presented.

[Experimental studies to set hygienic standards for benzylpenicillin in the air of a work area]. / Eksperimental'nye issledovaniia po gigienicheskomu normirovaniiu benzilpenitsillina v vozdukhe rabochei zony.

The character and level of benzylpenicillin toxic effect was studied in accordance with the methodic instruction for performance of the experiments on toxicological estimation and hygienic norms of antibiotics in the air of working areas in production premises. It was shown that the antibiotic was of low toxicity under conditions of a single exposure, did not cumulate and had no local irritating and resorbing effect. It was shown to be an allergen. Prolonged inhalation of benzylpenicillin in a concentration of 14 mg/m3 resulted in reversible changes in the function of the kidneys and liver of the animals, their sensitization and development of pronounced dysbacteriosis of the mouth and intestine mucosa. In a concentration of 1 mg/m3 benzylpenicillin had no general toxic and sensitizing effect but induced reversible changes in the normal autoflora. This allowed the authors to consider the above concentration to be maximum with respect to the antibacterial effect. On the basis of the experiments the maximum permissible norm (MPN) of the aerosol of benzylpenicillin disintegration was recommended at the level of 0.1 mg/m3.

[Comparative toxicity of oxytetracycline and its semisynthetic derivatives, methacycline and doxycycline]. / Sravnitel'naia toksichnost' oksitetratsiklina i ego polusinteticheskikh proizvodnykh metatsiklina i doksitsiklina.

The acute toxicity parameters of oxytetracycline and its semisynthetic derivatives was determined on laboratory animals of various species. The three antibiotics were described as belonging to the group of low toxic compounds according to the classification adopted in industrial toxicology. However, the absolute values of LD50 indicated that doxycycline was 5.6 or 2.8 times more toxic than oxyteyracycline or methacycline respectively. In addition, doxycycline had the most pronounced hepatoxic effect.

[Methodological bases for the hygienic standardization of antibiotics]. / Metodicheskie osnovy gigienicheskogo normirovaniia antibiotikov.

For determination of the maximum permissible concentrations of antibiotics it is necessary to develop some specific approaches conditioned by the peculiarities of the biological effect of antibiotics in addition to the use of the general principles of the hygienic rationing of the factors of the production environment. It is advised to determine the thresholds of the specific antibacterial and allergen effect of antibiotics in the acute experiment in addition to the threshold of the general toxic effect.

[Experimental data on hygienic norms for antibiotics of the tetracycline group]. / Eksperimental'nye materialy k gigienicheskomu normirovaniiu antibiotikov tetratsiklinovoi gfuppy

Toxicity of tetracyclines was studied experimentally on different species of laboratory animals. It was shown that tetracycline, oxytetracycline and chlortetracycline were close by their chemical structure and physico-chemical properties, as well as by the main toxicity parameters, i.e. acute toxicity, cumulative activity, skin-irritating and sensitizing effect. Under the conditions of subacute experiments the above 3 antibiotics induced evenly pronounced one direction changes in animals. The data obtained during the experiments provided recommendation of the level of 0.1 mg/m3 as the maximum allowable concentration (MAC) of oxytetracycline and chlortetracycline, i.e. the same level as the previously recommended for tetracycline.

[Experimental study of the embryotropic action of tetracycline]. / Eksperimental'noe issledovanie émbriotropnogo deistviia tetratsiklina

The general toxic and embryotropic effect of tetracycline was studied on unbred pregnant albino rats. The antibiotic was used in concentrations of 1 and 0.1 mg/m3, the maximum permissible concentration (MPC). The animals were exposed to tetracycline inhalation for 20 days of their pregnancy. On the basis of the results it was concluded that tetracycline in the concentration at the level of the MPC, i.e. 0.1 mg/m3 had under the experimental conditions a negative effect on the pregnant animals. In concentrations of 1 and 0.1 mg/m3 it had in addition an embryotropic effect. It was also shown that the pregnant animals were more sensitive to the antibiotic than the non-pregnant ones.

[Experimental study of the effect of rifampicin on the embryogenesis of white rats]. / Eksperimental'noe izuchenie vliianiia rifampitsina na émbriogenez belykh krys.

The embryotoxic and teratogenic effects of rifampicin were studied on Wistar albino rats exposed to the antibiotic inhalations during the whole period of gravidity. It was found that in the concentrations used (6.1 +/- 0.4 and 0.81 +/- 0.08 mg/m3) the antibiotic did not induce any increase in the rate of the fetus intrauterine death or any pronounced anomaly in the fetus development. Still, at higher concentrations there was a decrease in the anthropometric characteristics of the fetus, higher incidence of hemoperitoneum and disorders in liver and renal functions of the 2-month-old progeny. The damaging effect of rifampicin on the fetus should be considered as mediated since it was observed in the presence of disorders in the mother's body (changes in liver and renal function, suppressed phagocytosis).

[Microflora of theintestines of persons in contact with aminoglycosides and penicillin]. / Mikroflora kishechnika liudei, imeiushchikh kontakt s aminoglikozidami i penitsillinom

A total of 90 persons being in contact with aminoglycosides and penicillin were examined. It was found that such a contact resulted in dysbacteriosis of the intestine. The culture of Coli bacteria isolated from the persons had a low fermentative activity and lost their mobility. Bificol, a biological preparation proved to be promising in the treatment of persons with dysfunction of the intestine against the background of dysbacteriosis.