[Rapid methods for evaluation of hygienic standards of drugs in the air at the workplace]. / Uskorennye metody obosnovaniia gigienicheskikh normativov lekarstvennykh sredstv v vozdukhe rabochei zony.

System of calculating methods for staged prognostication of toxicometric parameters and hygienic standards of synthetic drugs was elaborated. This system gives possibility to substantiate quantitative criteria for determination of capacity and directions of investigations in pharmaceutical industry.

[The testing of the carcinogenicity of dispirotripiperazine derivatives by combined administration with sodium nitrite]. / Testirovanie kantserogennosti proizvodnykh dispirotripiperaziniia pri kombinirovannom vvedenii s nitritom natriia.

The cancerogenic activity of the dispirotripiperasinium derivatives prospidine and spirobromine was tested in concurrent use with sodium nitrite. The drugs were intragastrically administered once a week. It was combined with sodium nitrite, 35 mg/kg, to non-inbred rats of both sex during 24 months. A morphological study revealed no statistically significant reduction of latency and no increase in the incidence of tumors in laboratory animals. No cancerogenic effect of sodium nitrite was found.

[The carcinogenic activity of spirobromine]. / Kantserogennaia aktivnost' spirobromina.

The carcinogenic activity of spyrobromin was studied during the chronic experiment on 1.5-2-month-old rats and mice of both sexes. The drug was administered intragastrically and intraperitoneally once a week in the maximally tolerant dose for 24 months. Under the given experimental conditions spyrobromin can diminish the latent period of the development of tumours in the experimental rats at intraperitoneal administration. At intragastric administration of the drug no decrease was noted in the latent period and no increase of tumours was observed in the experimental groups of the animals as compared with control. Spyrobromin is considered to be a weak carcinogen. The oral route of administration is the most safe with respect to the oncogenic risk.

[The hematotoxic and nephrotoxic actions of dispirotripiperazine derivatives in a chronic experiment]. / Gematotoksicheskoe i neirotoksicheskoe deistvie proizvodnykh dispirotripiperaziniia v khronicheskom éksperimente.

The effects of dispirotripiperazine derivatives spirobromin and prospidin on the parameters of the peripheral blood and behavioral reactions in a chronic 12-month experiment were studied. The experiment was performed on noninbred rats of both sexes. The maximal tolerated doses of the drugs were administered by two routes (intragastrically or intraperitoneally). Hemoglobin, erythrocytes, leukocytes, platelets, reticulocytes, eosinophils were determined in the blood. The behavioral reactions were registered by the methods of the "open field" and the "open area". Under the conditions of the chronic experiment spirobromin and prospidin were shown to exert no significant effect on the parameters of the peripheral blood except a decrease in the amount of erythrocytes. It was noted that spirobromin exerted the most pronounced toxic action on erythrocytes. As to the behavioral reactions, after the administration of prospidin, the neurotoxic action on the rats was found after 12-14 months of observation.

[Methodological approaches to evaluating the sensitizing properties of new drug preparations in preclinical trials]. / Metodicheskie podkhody k otsenke sensibiliziruiushchikh svoistv novykh lekarstvennykh preparatov na stadii doklinicheskogo ispytaniia.

For testing allergenic activity of 18 drugs with various pharmacological properties the reaction of specific leukocyte agglomeration, specific leukocyte lysis reaction, determination of Mg2+ blood serum content and epicutaneous drug application were used. An attempt was made to establish the relationship between the development of immunological response and the time and duration of allergization, the dosage and routes of allergen administration and also to determine the optimal experimental conditions for appearance of the most pronounced response.

[Evaluation of the effect of the antihistaminic preparations dimebon and diprazin on embryogenesis in rats]. / Otsenka vliianiia antigistaminnykh preparatov dimebona i diprazina na émbriogenez krys.

A single administration of dimebon (800 mg/kg) to rats per os (2/3 of the LD50 isoeffective for females) raises the preimplantation death, whereas pipolphen increases the intrauterine lethality and inhibits the development of fetuses. Pipolphen in a dose of 175 mg/kg and dimebon in doses of 300-150 mg/kg (exceeding 25- and 300-150-fold, respectively, the therapeutic dose for man) do not exert any specific embryotropic action.

[Preclinical study of the safety of the antihistaminic preparation dimebon]. / Doklinicheskoe izuchenie bezvrednosti antigistaminnogo preparata dimebona.

The antihistaminic drug dimebon was subjected to toxicological study. It was demonstrated that as regards the level of the mean lethal doses dimebon can be attributed to little toxic substances. Administration of the drug in the doses approximating the therapeutic ones (1 and 5 mg/kg) for 2 months did not produce any alterations in rats, guinea-pigs or dogs. When administered in high doses (10 and 70 mg/kg) the drug provoked compensated abnormalities of some functions of the liver and kidneys in the presence of moderate and reversible structural changes in these organs. Dimebon did not exert any local irritating effect on the gastrointestinal tract. Administration of the drug in doses of 150 and 300 mg/kg at different times of pregnancy (days 1-7, 8-13, 14-19) did not produce any embryolethal or teratogenic effects.

[Carcinogenic activity of dioxidine]. / Izuchenie kantserogennoi aktivnosti dioksidina.

A study was made of the blastomogenic activity of dioxydin, a new antibacterial broad-action drug. Administration of dioxydin in doses of 20-100 mg/kg (exceeding 2-10-fold the therapeutic dose for humans) to mice and rats intragastrically for 18 months and intraperitoneally (2 years of observation) as well as combined administration of the drug to rats transplacentally and postnatally (1.5 years of observation) did not induce any neoplasms.

[Assessment of the effect of sex steroids on the sexual behavior of the rat at late periods of observation]. / Otsenka vliianiia polovykh steroidov na polovoe povedenie krys v otdalennye sroki nabliudeniia.

A study was made of sexual behavior of male rats exposed to prolonged (4 months) metandrostenolone (MAS) inhalations at the level Limch spec as of the effect of methyltestosterone (MT) on sexual behavior of the progeny following drug applications to the skin of pregnant rats in a dose at the level Limac spec. Methodological approaches to the appraisal of sexual behavior of rats are described. MAS (0.01 mg/m3) did not produce any deviations in sexual behavior of males. MT (1 mg/kg) applied during pregnancy had a masculinizing effect on the progeny females, that manifested in anatomical disorders of the urogenital area, thereby giving rise to alterations in sexual behavior of the progeny females and in that of their partners--intact males. The conclusion is made about high risk of the manifestations of specific effects of sexual steroids applied to the skin in the doses approximating the Limac spec.

[Mathematical model of the dose-time-effect relationship in the intramuscular administration of testosterone esters]. / Matematicheskaia model' zavisimosti doza-vremia-éffekt pri vnutrimyshechnom vvedenii éfirov testosterona.

Two equations of the dose-time-effect dependence during repeated intramuscular injections of testosterone esters are presented. The equation coefficients characterizing both properties of the drugs injected and individual features of the organs exposed to their action are interpreted. Moreover, two equations for calculating duration of the mitotic cycle of the test organ cells are given.

[Rat postnatal development after bonafton exposure]. / Postnatal'noe razvitie krys posle vozdeistviia bonaftona.

The first generation progeny of rats received days 10-13 of pregnancy a new antiviral drug bonaphthon (400 mg/kg) which exerts a toxic effect on females. The progeny did not show postnatal death or reduction of the life span. Moreover, no impairment of muscle work capacity, basal metabolism, cardiovascular system, peripheral blood parameters, or changes in the function of organs and systems were recorded. Morphological and functional deviations in the liver of 2-month-old progeny were unstable and got repaired by 3 months of age.

[Effect of bonafton on the bodies of pregnant animals]. / Vliianie bonaftona na organizm beremennykh zhivotnykh.

The toxicity of the original drug bonaphthon was studied in pregnant and nonpregnant mice and rats given the drug orally and intraperitoneally. In a dose of 100 mg/kg bonaphthon had no toxic effect on pregnant rats after 4-time administration per os, while in a single dose of 400 mg/kg the drug elicited side effects such as congestion phenomena and inconsistent dystrophic changes in the parenchymal organs. Toxic effects in the liver were most pronounced when the drug was administered in the earlier periods of pregnancy.

[Effect of bonaphthone on embryogenesis in white rats and mice]. / Vliianie bonaftona na émbriogenez belykh krys i myshei.

Results of testing the embryotropic activity of bonaphthone used in different doses (700; 400; 100; 50 and 2 mg/kg) are reported. With its oral introduction to pregnant rats bonaphthone, given in doses at the level of the therapeutid one (2 mg/kg) and exceeding it by as much as 25 times (50 mg/kg), was found not to produce any damaging effect on the fetus. With its action in doses of 100 and 400 mg/kg a slight embryotoxic effect was noted. In the sublethal dose of 700 mg/kg the preparation displays a moderate embryotoxic action and produces a number of circulatory changes in the fetuses. It is concluded that bonaphthone displays no teratogenic properties.