Safety Evaluation of Eucalyptus globulus Essential Oils through Acute and Sub-acute Toxicity and Skin Irritation in Mice and Rats

Page: [187 - 195] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: The Eucalyptus globulus extractions have been used by the traditional healers to treat diseases in the study area. Our previous study revealed that the essential oil has antimicrobial and antifungal activity. This study determined phytochemical analysis, skin irritation, acute and subacute toxicity of Eucalyptus globulus essential oil in mice and rats.

Methods: The phytochemicals were analyzed using GC-MS mass spectrometry. The acute toxicity study was determined at three dose levels of 1500 mg/kg, 1750mg/kg, and 2000 mg/kg. The essential oil limit test at a dose of 1000 mg/kg was administered to mice for 28 consecutive days for sub-acute toxicity study. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were analyzed for histopathological analyses. The 5% ointment formulation was applied to the rat skin to determine skin irritation effects.

Results: The Eucalyptus globulus essential oil showed no effect on the mice at a dose of 1500mg/kg and below, but caused signs of toxicity and death at a dose of 1750mg/kg and above compared to the controls (p<0.05). The LD50 value was 1650 mg/kg. There was no significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control at 1000 mg/kg subacute toxicity study. No histopathological changes were detected in the organs tested. The 5% ointment formulation did not show any abnormal skin reaction.

Discussion: In the present study, the Eucalyptus globulus essential oil was comparable with other studies in terms of both chemical composition and its effects on sub-acute and topical application.

Conclusion: This toxicity study demonstrated that Eucalyptus globulus essential oil is nontoxic at a relatively lower concentration.

Keywords: Acute toxicity, essential oil, Eucalyptus globules, skin irritation, sub-acute toxicity, GC/MS.

Graphical Abstract

[1]
Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981-2002. J Nat Prod 2003; 66(7): 1022-37.
[http://dx.doi.org/10.1021/np030096l] [PMID: 12880330]
[2]
Joshi CS, Priya ES, Venkataraman S. Acute and subacute toxicity studies on the polyherbal antidiabetic formulation diakyur in experimental animal models. J Health Sci 2007; 53: 245-9.
[http://dx.doi.org/10.1248/jhs.53.245]
[3]
OECD (Organization for Economic Cooperation and Development). OECD guidelines for acute toxicity of chemicals; Organization for economic co-operation and development: Paris, France 2001; No 420
[4]
OECD (Organization for Economic Cooperation and Development). OECD Guideline for Testing of Chemicals Repeated Dose 28-Day Oral Toxicity Study in Rodents; Organization for Economic Cooperation and Development: Paris, France. 2008; No 407.
[5]
Akin M, Aktumsek A, Nostro A. Antibacterial activity and composition of the essential oils of Eucalyptus camaldulensis Dehn and Myrtus communis L. growing in Northern Cyprus. Afr J Biotechnol 2010; 9: 531-5.
[6]
Denardi L, Marchiori JN. Anatomia Ecolo´ gica de madeira de Blepharocalyx salicifolius (H. B. k.) Berg. Cienc Florest 2005; 15: 119-27.
[http://dx.doi.org/10.5902/198050981829]
[7]
Arfao AT, Nola M, Djimeli CL, Nougang ME, Fokou JB. Cultivability of Salmonella typhi, Vibrio cholerae and enteropathogenic Escherichia coli in water microcosm in the presence of Eucalyptus microcorys leaves extract: Effect of the concentration of leaves extract and incubation temperature. Int J Res Biosci 2013; 2: 32-46.
[8]
Siurin SA. [Effects of essential oil on lipid peroxidation and lipid metabolism in patients with chronic bronchitis Klin Med (Mosk) 1997; 75(10): 43-5.
[PMID: 9490339]
[9]
Su Y, Li Q, Yao C, Lu Y, Hong J. Antitumor action of ethanolic extractives from camphor leaves. Chemical Industry and Engineering Progress 2006; 25(2): 200.
[10]
Li H, Huang L, Zhou A, Li X, Sun J. [Study on antiinflammatory effect of different chemotype of Cinnamomum camphora on rat arthritis model induced by Freund’s adjuvant Zhongguo Zhongyao Zazhi 2009; 34(24): 3251-4.
[PMID: 20353012]
[11]
Singla N, Thind RK, Mahal AK. Potential of eucalyptus oil as repellent against house rat, Rattus rattus. ScientificWorldJournal 2014; 2014249284
[http://dx.doi.org/10.1155/2014/249284] [PMID: 24523633]
[12]
Ambaye TG, Bezabh AM, Mekonen F. Phytochemical and antimicrobial potentials leaves extract of eucalyptus globulus oil from maichew tigray Ethiopia. Int J Complement Alt Med 2016; 2(3): 00056.
[13]
Fentahun M, Ayele YB, Amsalu N, Alemayehu A, Amsalu G. Antibacterial evaluation and phytochemical analysis of selected medicinal plants against some pathogenic enteric bacteria in gozamin district, Ethiopia. J Pharmacovigil 2017; 5(5): 1-6.
[14]
Alemayehu B, Gelibo T, Kanche ZZ. Eucalyptus globulus oil versus bleach use as antiseptic agents in podoconiosis treatment: An interventional study in wolaita zone, Southern Ethiopia. Am J of Biomed Life Sci 2017; 5(6): 113-8.
[http://dx.doi.org/10.11648/j.ajbls.20170506.11]
[15]
Gebremickael A. Acute and sub-chronic oral toxicity evaluation of eucalyptus globulus essential oil-water emulsion in mice. J Cytol Histol 2017; 8(2): 1-7.
[http://dx.doi.org/10.4172/2157-7099.1000459]
[16]
Underwood W, Anthony R, Cartner S, et al. AVMA guidelines for the euthanasia of animals. 2013 edition. Schaumburg, IL: American Veterinary Medical Association 2013.
[17]
ILAR, Institute for Laboratory Animal Research. Guide for the care and use of laboratory animals. Washington, DC, USA: The National Academy Press 1996.
[18]
Bora A, Deshmukh S, Swain K. Recent advances in semisolid dosage form. Int J Pharm Sci Res 2014; 5: 3594-608.
[19]
Nair R, Sevukarajan M, Mohammed B, Kumar J. Formulation of Microemulsion based vaginal gel in-vitro and in-vivo evaluation. Der Pharmacia Lettre 2010; 2: 99-105.
[20]
Muhammad H, Makun H, Busari M, Abdullah A. Acute and sub-acute toxicity studies of aqueous and methanol extracts of Nelsonia campestris in rats. J Acute Dis 2016; 5(1): 62-70.
[http://dx.doi.org/10.1016/j.joad.2015.08.006]
[21]
Khan AM, Khatun S, Hossain MK, Rahman ML. Characterization of the Eucalyptus (E. Globulus) leaves oil. J Bangladesh Chem Soc 2012; 25: 97-100.
[http://dx.doi.org/10.3329/jbcs.v25i1.11780]
[22]
Song A, Wang Y, Liu Y. Study on the chemical constituents of the essential oil of the leaves of Eucalyptus globulus Labill from China. Asian J Tradit Med 2009; 4: 34-140.
[23]
Boukhatem MN, Amine FM, Kameli A, Saidi F, Walid K, Mohamed SB. Quality assessment of the essential oil from Eucalyptus globulus Labill of Blida (Algeria) origin. Intern Lett Chem. Phy Astron 2014; 17: 303-15.
[24]
Joshi A, Sharma A, Bachheti R, Pandey DP. A comparative study of the chemical composition of the essential oil from Eucalyptus globulus growing in Dehradun (India) and around the world. Orient J Chem 2016; 32: 31-340.
[http://dx.doi.org/10.13005/ojc/320137]
[25]
Subramanian PA, Gebrekidan A, Nigussie K. Yield, contents and chemical composition variations in the essential oils of different Eucalyptus globulus trees from Tigray, Northern Ethiopia. J Pharm Biomed Sci 2012; 17: 17.
[26]
Mekonnen A, Yitayew B, Tesema A, Taddese S. In vitro antimicrobial activity of essential oil of Thymus schimperi, Matricaria chamomilla, Eucalyptus globulus, and Rosmarinus officinalis. Int J Microbiol 2016; 20169545693
[http://dx.doi.org/10.1155/2016/9545693] [PMID: 26880928]
[27]
Duan WL, Liang XM. Technical guidelines assembly of veterinary medicine research. Beijing: Chemical Industry Press 2011.
[28]
Hu Z, Feng R, Xiang F, et al. Acute and subchronic toxicity as well as evaluation of safety pharmacology of eucalyptus oil-water emulsions. Int J Clin Exp Med 2014; 7(12): 4835-45.
[PMID: 25663980]