The Journal “Toksikologicheskiy vestnik” (Toxicological Review)


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Jan–Feb, 2019
# 1


TOXICOLOGICAL CHARACTERISTIC OF DESIGNER DRUGS FROM THE GROUP OF SYNTHETIC OPIOIDS
Authors: Golovko A. I. , Ivanov M. B. , Rejniuk V. L. , Rejniuk V. L. , Ivnitsky Yu. Yu. , Ivnitsky Yu. Yu. , Barinov V. A. , Borodavko V. K. , Borodavko V. K.

Toxicological characteristic of designer drugs from the group of synthetic opioids is presented. The historical aspects of illicit drug trafficking are considered. In the illicit drug market of EU countries 38 synthetic opioids, 22 of them belonging to fentanyl derivatives, have been revealed for the period 2005-2017. The widespread use of synthetic opioids among drug addicts has been accompanied by an increase in the number of fatal overdoses. In the United States the number of fatal poisonings by synthetic opioids of fentanyl series increased by 40.3 times between 1999 and 2017. The similar situation is emerging in other countries. This is due to the fact that the biological activity and toxicity of synthetic opioids far exceed those of morphine and heroin. The differences between the metabolism of heroin and synthetic opioids are considered. Data on the toxicity of synthetic opioids are presented. The neurotransmitter mechanisms of their respiratory depression, including disorders of opioid, GABAergic, glutamatergic and serotoninergic neurotransmitter systems are discussed. A brief description of the antidote activity of opioid receptor antagonists in acute poisoning by synthetic opioids is given.

Keywords: designer drugs from the group of synthetic opioids, opioid epidemic, metabolism and toxicity of opioids, respiratory depression, antidotes for the treatment of acute poisoning with synthetic opioids


EXPERIMENTAL EVALUATION OF CHRONIC ORAL TOXICITY AND LONG-TERM EFFECTS OF SOLID ROCKET FUELS COMPONENT
Authors: Maslennikov A. A. , Antonov V. A. , Antonov V. A. , Bocharova L. Yu. , Tochilkina L. P. , Novikova O. N. , Khodykina N. V. , Grishina M. A. , Grishina M. A. , Pocheptsov A. Ya.

The chronic oral toxicity and long-term effects of the basic lead-nickel salt of phthalic acid have been investigated by long-term oral ingestion of white outbred rats. The compound at doses of 1.0 mg/kg; 0.3 mg/kg and 0.1 mg/kg have changed the physiological, behavioral, hematological, biochemical, immunological parameters, as well as the relative weight of internal organs of animals in the six months experiments. The threshold of chronic oral toxicity of the substance is set at 0.1 mg / kg. The study of long-term effects revealed the absence of its mutagenic activity both at the gene (Ames test) and chromosomal (dominant lethal method) levels. In addition, the analyzed compound did not adversely affect the reproductive function of male rats. When entering the body of females during gestation, the toxicant did not reveal embryo-lethal and teratogenic properties. However, chronic administration of the compound into the body of non-pregnant animals at a dose of 1.0 mg/kg contributed to a significant decrease relative to the control of the mass and disk diameter of the placenta, which indirectly indicated the functional inferiority of the organ. Therefore, the considered level of the substance is defined as a threshold for gonadotoxic effect. The obtained data are taken into account in developing of hygienic standard of the estimated component of solid rocket fuels in water reservoirs.

Keywords: water, basic lead-nickel salt of phthalic acid, chronic oral toxicity, long-term effects, threshold doses


CITOTOXICITY OF INDIUM-111-LABELED AUTOLOGOUS WBC
Authors: Luneva K. A. , Luneva K. A. , Ternovskaya K. E. , Klement O. E. , Klement O. E. , Lunev A. S.

A.I. Burnasyan Federal Medical Biophysical Center|, 123098, Moscow, Russian Federation K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology|, 109472, Moscow, Russian Federation The radiopharmaceutical precursor «Oxind, 111In» is a complex compound for labeling autologous leukocytes of human blood and their subsequent introduction for non-specific visualization and localization of inflammation foci of different nature by single-photon emission computed tomography (SPECT). The cytotoxic effect of lyophilisate for preparation of radiopharmaceutical preparation «Oxind, 111In» and its radiopharmaceutical precursor on rabbit blood leukocytes has been investigated. In the course of studies of the cytotoxicity of the lyophilisate for the preparation of a radiopharmaceutical precursor with successively increasing concentrations of the main substance, 8-hydroxyquinoline, the permissible concentrations have been determined and the absolutely cytotoxic concentration was achieved. In the study of the cytotoxic effect of the precursor of radiopharmaceutical on two dosages that differ by 10 times in volume activities (MBq / ml), the absence of cytotoxic effects has been confirmed.

Keywords: 8-hydroxyquinoline, Indium-111, 111In-oxin, oxind, cytotoxicity, safety use, leukocytes, radiopharmaceutical, lyophilisate, SPECT, preclinical studies


NEUROTOXICOLOGICAL PROFILE OF 5-IO2A-ANTAGONIST OF IMIDAZOBENZIMIDAZOLE DERIVATIVE
Authors: Spasov A. A. , Yakovlev D. S. , Yakovlev D. S. , Maltsev D. V. , Maltsev D. V. , Miroshnikov M. V. , Miroshnikov M. V. , Sultanova K. T. , Sultanova K. T. , Zhukovskaya O. N. , Zhukovskaya O. N. , Anisimova V. A. , Anisimova V. A. , Nechaeva K. A. , Nechaeva K. A.

The article presents the results of a study of the neurotoxicological profile of a new 5-HT2A-antagonist (compound I) using the method of multi-test observation by «S. Irwin». The test parameters were evaluated in parallel groups, receiving the compound in doses beginning with the average effective dose (ED50) and with a multiple increase of 2, 5, 7.5 and 10 times. The study revealed that the neurotoxicological properties of compound I are characterized by dose-dependent activity. It has been shown that neurotoxicological changes in the behavior of the animals did not occur with the administration of compound I at average effective dose of 10 mg / kg and doses, exceeding the effective by 2 and 5 times; the animals welfare corresponds to that of the control group. The most significant effects by the administration of the studied compound developed in high doses, exceeding the effective by 7.5 and 10 times. The limits of the minimum toxic dose (TDmin) for compound I by oral administration has been found to be 50 mg / kg

Keywords: neurotoxicity research, the method of multi-test observation according to «S. Irwin», imidazobenzimidazole derivative, compound I, average effective dose, minimal toxic dose, dose-dependent effect


THE STUDY OF THE ACUTE TOXICITY OF NIFUROXAZIDE IN FORM OF SUSPENSION
Authors: Sitnikova E. A. , Sitnikova E. A. , Rogozhnikova E. P. , Rogozhnikova E. P. , Mardanly S. G. , Mardanly S. G. , Kiseleva V. A. , Kiseleva V. A.

A comparative study of acute toxicity of nifuroxazide preparations in form of suspension has been carried out. Mature individuals of white mice (weighing 18-20 g at the age of 8-9 weeks) and rats (weighing 160-180 g at the age of 13-14 weeks) of both sexes were under observation. The administration of the suspensions was performed in increasing doses by Litchfield-Wilcoxon, dosing was carried out by volume on the total mass of the suspension. The recorded indicators were mortality, time of death of animals, symptoms of poisoning, autopsy, description of animals at the end of the study, determination of mass coefficients of internal organs. The compared drugs («Nifuroxazide», suspension for oral administration 200 mg/5 ml, LP 004858 dated 23.05.2018 and «Enterofuril», suspension for oral administration 200 mg/5 ml N014624/02 dated 06.11.2008) are equivalent in terms of acute toxicity, belonging to class VI of relatively harmless drugs, have similarities in the parameters of acute toxicity, the picture of intoxication is the same, and there are not detected signs of damage of internal organs.

Keywords: acute toxicity, nifuroxazide, preclinical studies


EXPERIMENTAL STUDIES OF THE COMBINED ACTION OF MULTICOMPONENT CHEMICAL AEROSOL AND LOW TEMPERATURE
Authors: Nikolaeva N. I. , Rakitskii V. N. , Filin A. S.

The comparative complex cytomorphological study of the combined action of low temperature and mixed aerosol containing sulfuric compounds has been conducted. The experiments were made on animals adapted and not adapted to cold action. The analysis of the obtained results allows to state that the combined effect of the factors studied has a pronounced effect on the development of disorders in the bronchopulmonary, cardiovascular, and liver systems. The data obtained show unidirectional changes in cytomorphological parameters with changes in the bronchopulmonary system. However, in non-adapted animals, structural and metabolic changes in the lungs, liver, heart and subcutaneous connective tissue were recorded earlier (60 days) than in the adapted ones (120 days).

Keywords: multicomponent chemical aerosol, combined action, pathomorphological studies, histoenzymatic analysis


ASSESSMENT OF TOXICITY AND HAZARD OF TECHNICAL PRODUCT OF TRIAZINONE DERIVATIVE
Authors: Rakitskii V. N. , Apishina T. M. , Apishina T. M. , Chkhvirkiya E. G. , Chkhvirkiya E. G. , Sinitskaya T. A. , Mukhina A. A. , Mukhina A. A.

Experimental assessment of toxicity and hazard of technical product of triazinone’s derivative at its peroral administration into warm-blooded animals’ bodies (male rats) has been conducted to determine the character of the substance biological action. Its acute peroral toxicity was at the level of LD50 -1693 ± 470 mg/kg of body weight, hazard class – 4 according to Hygienic Classification of Pesticides (Sanitary Rules & Standards 1.2.2584-10). Effective dose was 62.5 mg/kg b.w., non-effective dose (NOEL) was 12.5 mg/kg b.w. ADI was 0.1 mg/kg b.w.

Keywords: technical product, triazinone’s derivative, acute peroral toxicity (LD50), laboratory animals, peroral administration, toxicity


’din MORPHOLOGIC SPECIFICITIES OF HEPATOPROTECTIVE EFFECTS OF ANTIHYPOXANTS IN EXPERIMENTAL ACUTE LIVER DAMAGE WITH CARBON TETRACHLORIDE
Authors: Repina E. F. , Khusnutdinova N. Yu. , Timasheva G. V. , Baigil S. S. , Baigil S. S. , Karimov D. O. , Musina L. A. , Musina L. A. , Myshkin V. A. , Bakirov A. B. , Gimadieva A. R.

The article presents the results on liver morphologic changes in acute carbon tetrachloride damage and its preventive correction by antihypoxants: complex oxymethyluracil agents (with sodium succinate and ascorbic acid). It has been shown that carbon tetrachloride causes pronounced morphologic changes in the liver and preventive use of the antihypoxants studied decreases intensity and prevalence of dystrophic processes in liver tissues. The analysis of comparative efficiency of the agents studied has been carried out.

Keywords: carbon tetrachloride, antihypoxants, oxymethyluracil, sodium succinate, ascorbic acid, liver, morphologic structure


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Magazine Founder: FBEPH “Russian Register of Potentially Hazardous Chemical and Biological Substances”