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JOURNAL

ISSN 2077-7477 (Print)
ISSN 2077-7485 (Online)

A journal "Dovkillia ta zdorovia" (Environment & Health) publishes the articles on the problems in the field of medical ecology, hygiene, health protection and ecological safety.

Founder of the Journal:
State Institution "O.M. Marzeiev Institute for Hygiene and Medical Ecology of the National Academy of Medical Sciences of Ukraine"

Frequency of publication:
quarterly

Environment & HealthISSN: 2077-7477 eISSN: 2077-7485
No: 1 (102)   -   FEBRUARY, 2022   -   Pages: 20-30
Assessment of toxicity and mechanism of the drug (camphoric acid derivative) effect on the organism
Palagina ..1, Kudria M.Ya.1
1 State Institution V. Danilevsky Institute of Endocrine Pathology Problems, National Academy of Medical Sciences of Ukraine, Kharkiv

ABSTRACT:
The drugs, their active ingredients under conditions of manufacture and pharmaceutical waste at the ingress in the environment can be hazardous to the human health. The toxicological examination enables to predict the risk of their adverse effects on the organism with a determination of the prior criteria of hazard.

Objectives: We defined the probable toxic effects and the mechanism of their formation under various conditions of the exposure of the original anti-diabetic drug based on a camphoric acid derivative (Diacamph - DCMPh) under various conditions of its exposure.

Methods: The peculiarities of DCMPh effect on the organism were studied in the acute, sub-acute, and chronic experiments under different conditions of the drug introduction to animals by the indicators characterizing a state of the organism in a whole and the separate organs and systems of the organism and individual organs and systems, including prooxidant- antioxidant and immune systems. Its possible allergenic and mutagenic effects were studied in a separate run of the experiments.

Results: Our studies showed that DCMPh is virtually non-toxic in terms of an acute toxicity, does not accumulate, has no local irritant, mutagenic and allergenic effects, but is capable of the skin resorption. Adverse effect of DCMPh on the organism under its oral and inhalation introduction are realized through the disturbance of the prooxidant-antioxidant balance and cellular components of the immunological resistance. We determined a high sensitivity of lungs to the inhalation impact of DCMPh, taking into account an increase of the free radical oxidation in the organ tissue on the background of the weakening of the antioxidant system and a decrease of the functional reserve of neutrophils manifested in the aftereffect period. The high sensitivity of the lungs to the inhalation effect of DCMPh was determined taking into account the increase in free radical oxidation in the organ tissue on the background of the weakening of the antioxidant system and the decrease in the functional reserve of neutrophils, which manifests itself during the aftereffect period.

Conclusions: Taking into account the mechanism of toxic action, the maximum permissible concentration of DCMPh in the air of the working area was substantiated at the level of 0.4 mg / m3, hazard class II.

KEYWORDS:
antidiabetic drug camphoric acid derivative; toxicity; mechanism of toxic effect
REFERENCES:
1. Bhusnure O.G., Dongare R.B., Cholve S.B. and Giram P.S. Chemical Hazards and Safety Management in Pharmaceutical Industry. J. Pharmacy Res. 2018 ; 12 (03) : 357 - 369.
2. Nahorna A.M., Sokolova M.P., Vitte P.M., Kononova I.H. and Piatnytsia-Horpynchenko N.K. Stan profesiinoi zakhvoriuvanosti v period zakonodavchykh zmin v Ukraini [A State of Occupational Diseases During the Legislative Changes in Ukraine]. Ukr. zhurn. z probl. medytsyny pratsi. 2016 ; 1 (46) : 3 - 17 (in Ukrainian). DOI : https://doi.org/10.33573/ujoh2016.01.003
3. Nahorna A.M. and Kononova I.H. Profesiini zakhvoriuvannia : stan, problemy vyiavlennia, reiestratsii ta obliku v suchasnykh umovakh [Occupational Diseases: State, Problems of Detection, Registration and Accounting Under Modern Conditions]. Okhorona pratsi. 2018 ; 5 : 48 - 51 (in Ukrainian).
4. Gould J., Callis C.M., Dolan D.G., Stanard B. and Weideman P.A. Special Endpoint and Product Specific Considerations in Pharmaceutical Acceptable Daily Exposure Derivation (Review). Regul. Toxicol. Pharmacol. 2016; 79 (1) : 79 - 93. DOI : https://doi.org/10.1016/j.yrtph.2016.05.022
5. Asfaw S., Enquselassie F., Tefera Y., Gizaw G., Wakuma S. and Woldemariam M. Determinants of Chronic Respiratory Symptoms Among Pharmaceutical Factory Workers. J. Trop. Med. 2018 ; 3 : 1 - 10. DOI : https://doi.org/10.1155/2018/3815689
6. Nahorna A.M., Sokolova M.P. and Kononova I.H. Epidemiolohichni doslidzhennia profesiinoho zdorovia v Ukraini [Epidemiological Studies of the Occupational Health in Ukraine. Ukr. zhurn. z probl. medytsyny pratsi. 2018 ; 4 (57) : 3 - 20 (in Ukrainian). DOI : https://doi.org/10.33573/ujoh2018.04.003
7. Sussman R.G., Schatz A.R., Kimmel T.A., Ader A., Naumann B.D., and Weideman P.A. Identifying and Assessing Highly Hazardous Drugs Within Quality Risk Management Programs. Regul. Toxicol. Pharmacol. 2016 ; 79 (Supl. 1.) : 11 - 18. DOI : https://doi.org/10.1016/j.yrtph.2016.05.025
8. Zazuliak T.S. Vprovadzhennia suchasnykh vymoh do metodyk kilkisnoho kontroliu shkidlyvykh khimichnykh chynnykiv u povitri robochoi zony farmatsevtychnykh pidpryiemstv [Implementation of Modern Requirements for Methods of Quantitative Control of Harmful Chemical Factors in the Air of the Working Area of Pharmaceutical Enterprises]. Ukr. zhurn. z probl. medytsyny pratsi. 2020 ; 16 (1) : 33 - 43 (in Ukrainian). DOI : https://doi.org/10.33573/ujoh2020.01.033
9. Beek T., Weber F.-A., Bergmann A., Hickmann S., Ebert I., Hein A. and Küster A. Pharmaceuticals in the Environment - Global Occurrences and Perspectives. Environ. Toxicol. Chem. 2016 ; 35 (4) : 823 - 835. DOI : https://doi.org/10.1002/etc.3339
10. Kalapko O.M., Shtryhol S.Yu. and Merzlikin S.I. Porivnialne doslidzhennia N, N-(etan-1,2-dyil)bis(khinolin-2-karboksamidu), diacamph hidrokhlorydu ta metforminu na modeli insulinorezystentnosti [Comparative Study of N, N'-(Ethane-1,2-Diil)bis(Quinoline-2-Carboxamide), Diacamph Hydrochloride and Metformin in a Model of Insulin Resistance]. Farmakolohiia ta likarska toksykolohiia. 2017 ; 3 : 56 - 63 (in Ukrainian).
11. Guengerich F.P. Mechanisms of Drug Toxicity and Relevance to Pharmaceutical Development. Drug Metab. Pharmacokinet. 2011 ; 26 (1) : 3 - 14. DOI : https://doi.org/10.2133/dmpk.DMPK-10-RV-062
12. Doklinichni doslidzhennia likarskykh zasobiv : metodychni rekomendatsii [Preclinical Studies of Medicines: Guidelines]. Stefanova O.V. (Ed.). Kyiv : Avitsena ; 2002 : 528 p. (in Ukrainian).
13. Klimkina N.V. and Plitman S.Y. Kolorimetricheskiy metod opredeleniya gistamina v krovi i organakh laboratornykh zhivotnykh [Colorimetric Method for the Determination of Histamine in the Blood and Organs of Laboratory Animals]. In : Biokhimicheskiye metody issledovaniya v gigiyene [Biochemical Research Methods in Hygiene]. Moscow : Meditsina ; 1973 : 87 p. (in Russian).
14. Frolov V.M., Richnev V.E. and Bala M.A. Issledovaniye tsirkuliruyushchikh immunnykh kompleksov pri rozhe: diagnosticheskoye i prognosticheskoye znacheniye [Study of Circulating Immune Complexes in Erysipelas: Diagnostic and Prognostic Significance]. Laboratornoye delo. 1986 ; 3 : 159 - 161 (in Russian).
15. Vladimirov V.A. and Suslova T.B. Reaktsii tsepnogo okisleniya lipidov v membrannykh strukturakh kletki [Lipid Chain Oxidation Reactions in Cell Membrane Structures]. In : Sverkhslaboye svecheniye v biologii: trudy MOIP [Ultra-Weak Glow in Biology: Works of MOIP]. Moscow : Nauka ; 1974 : 38-51 (in Russian).
16. Sovremennyye metody v biokhimii [Modern Methods in Biochemistry]. V.N. Orekhovich (Ed.). Moscow : Meditsina ;1977 : 392 p. (in Russian).
17. Moshynska O.V., Tretiak N.N., Anoshina M.Y. and Yagovdick M.V. Hemoglobin-Induced Lipid Peroxidation in Anemia. Likarska sprava. 2001 ; 4 : 39 - 43.
18. Misheneva V.S. and Goryukhina T.A. Nalichie glutationa v normalnikh i opukholevykh tkanyakh cheloveka i zhivotnykh [The Presence of Glutathione in Normal and Tumor Tissues of Humans and Animals]. Voprosy onkologii. 1968 ; 14 (10) : 46 49 (in Russian).
19. Hansen L.G. and Warwick W.J. A Fluorometric Micromethod for Fat Tocopherol. Clin. Biochem. 1970 ; 30 : 225 - 229. DOI : https://doi.org/10.1016/S0009-9120(70)80031-5
20. Korolyuk M.A., Ivanova L.I., Mayorova I.G and Tokarev V.E. Metod opredeleniya aktivnosti katalazy [Method for the Determination of Catalase Activity]. Laboratornoye delo. 1988 ; 1 : 16 - 19 (in Russian).
21. Kostyuk V.A., Potopovich A.I. and Kovaleva Zh.V. Prostoy i chuvstvitelnyy metodopredeleniya superoksiddismutazy. osnovannyy na reaktsii okisleniya kvertsitina [A Simple and Sensitive Method for the Determination of Superoxide Dismutase Based on the Oxidation Reaction of Quercetin]. Voprosy meditsinskoy khimii. 1990 ; 36 (2) : 88 - 91 (in Russian).
22. Lemeshko V.V. Sistema mikrosomalnogo okisleniya pri razvitii i starenii organizma [Microsomal Oxidation System During Development and Aging of the Organism]. Biokhimiya. 1980 ; 45 (11) : 1964 - 1969 (in Russian).
23. Frimmel G. Immunologicheskie metody [Immunological Methods]. Moscow : Meditsina ; 1987 : 382 - 385 (in Russian).
24. Menshikov V.V., Delektorskaya L.I. and Zolotnitskaya R.P. Laboratornyye metody issledovaniya v klinike : spravochnik [Laboratory Research Methods in a Clinic: Handbook]. Moscow : Meditsina ; 1987 : 386 p. (in Russian).
25. Chernushenko E.F. and Kogosova L.S. Immunologicheskiye issledovaniya v klinike [Immunological Tests in a Clinic]. Kiev : Zdorovia ; 1978 : 20 - 21 (in Russian).
26. Kuzovkova N.A. Otsenka aktivnosti estestvennykh killerov kolorimetricheskim metodom [Estimation of Activity of Natural Killers by Colorimetric Method]. Immunologiya. 1991 ; 4 : 59 - 61 (in Russian).
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