Importance of the toxicological tests in the application and safety of ozone therapy

Authors

  • Silvia Menendez-Cepero Retired from National Center for Scientific Research and now collaborator of this Center
  • Zullyt Zamora National Center for Scientific Research
  • Frank Hernandez Retired from National Center for Scientific Research

DOI:

https://doi.org/10.7203/jo3t.2.3.2018.10009

Keywords:

Ozone therapy, toxicological studies, ozone rectal insufflation, ozone major autohemotherapy, ozone intraperitoneal application, National Health Regulatory Agencies.

Abstract

Until today, there is not any official registry of the different routes of systemic ozone therapy. With the aim to prove the safety of this therapy, several ways of ozone (O3) applications were evaluated, such as rectal insufflation (RI), major autohemotherapy (M-AHT) and intraperitoneal application (IP). For RI, some toxicological tests were performed such as: acute, sub-chronic, mutagenic (bone marrow chromosomic aberrations and micronucleus), teratogenic  and irritation studies (at 40 mg/L and 10 mL during 15 days). For M-AHT, acute toxicological (in rats with 21, 47 and 64 mg/L and a volume of 2 mL with daily evaluation up to 15 days) and mutagenic (chromosomal aberration analysis, micronucleus assay and sister chromatid exchange test) studies were performed. For IP application, subchronic (O3 was administered during 15 days in mice at concentrations of 11, 29 and 35 mg/L and volumes of 80 mL/kg) and genotoxic (cytotoxic and clastogenic activity) studies were evaluated. All the toxicological studies performed for the O3 RI fulfilled the requirements established for an official registry (no deleterious effects were observed). However, more toxicological studies must be done with respect to M-AHT and IP O3 applications in order to prove the complete safety of these ways.

Downloads

Download data is not yet available.

Author Biographies

Silvia Menendez-Cepero, Retired from National Center for Scientific Research and now collaborator of this Center

Full Research and PhD in Chemistry

Zullyt Zamora, National Center for Scientific Research

Natural Product Department, Full Resaercher, PhD in Veterinary

Frank Hernandez, Retired from National Center for Scientific Research

Full Research and PhD in Biochemistry

References

Razumovskii SD, Zaikov GE. Ozone and its reaction with organic compounds. Moscow (RU): Nauka; 1974.

Pryor WA. Ozone in all its reactive splendor. J Lab Clin Med. 1993;122:483-486.

Bocci V. Is it true that ozone is always toxic? The end of a dogma. Toxicol Appl Pharm. 2006;216:493-504.

Viebahn R. The use of ozone in Medicine. 3rd English ed. Iffezheim (DE): ODREI-Publishers; 1999.

Mattassi R. Ozonoterapia. Milano (IT): Organizzazione Editoriale Medico Farmaceutico; 1985.

Aubourg P. L'ozone medical: Production, posologie, modes d'applications cliniques. Bull Med Soc Med Paris. 1938;52:745-749.

Menendez S, Leon OS, Fernandez JL, Copello M, Weiser MT. Advances of Ozone Therapy in Medicine and Dentistry. La Havana (CU): Palacio de las Convenciones; 2016. 513 p. ISBN: 978069278138859999.

Victorin K. Review of genotoxicity of ozone. Mutat Res. 1992;277:221-238.

Wright DT. Ozone stimulates release of platelet activating factor and activates phospholipases in guinea pig tracheal epithelial cells in primary culture.Toxicol Appl Pharm. 1994;127:27-35.

McBride DE, Koenig JQ. Inflammatory effects of ozone in the upper airways of subjects with asthma. Am J Respir Crit Care Med. 1994;149:1192-1197.

Devlin RB, Folinsbee L, Biscardi F, Hatch G, Becker S. Inflammation and cell damage induced by repeated exposures of humans to ozone. Inhal Toxicol. 1997;9:211-235.

Harkema JR, Plopper CG, Hyde DM, St George JA. Response of macaque bronchiolar epithelium to ambient concentration of ozone. Am J Pathol. 1993;143:857-866.

Re L. Molecular Aspects and New Biochemical Pathways Underlying Ozone Effects. Clin Exp Pharmacol. 2018;8:248-252.

Centro de Toxicología Experimental (CETEX). Codigo de las buenas practicas de laboratorio. La Havana (CU): Centro nacional para la produccion de animales de laboratorio (CENPALAB); 1992.

Ministerio de Salud Publica. Codigo de las buenas practicas de laboratorio. Resolución 152 del 17 de septiembre de 1992. La Havana (CU): Ministerio de Salud Publica; 1992.

Fox JG, Cohen BJ, Loew FM. Laboratory animal medicine. Chapter 4. Biology and diseases of rats. ACLAM Series. Orlando (FL): Academic Press; 1984.

Nelson H, Hayes R. Short term repeated dosing and subchronic toxicity studies. In: Hayes W. Principles and Methods of Toxicology. 3rd ed. New York (NY): Raven Press; 1994. p. 649-762.

ECETOC. Recommendations for the harmonization of international guidelines for toxicity studies. Monograph 7. ECETOC: Brussels (BE); 1985.

OECD. Test No. 407: Repeated dose 28-day oral toxicity study in rodents. OECD Guidelines for the testing of chemicals. Section 4. Paris (FR): OECD Publishing; 2008. Available from: https://doi.org/10.1787/9789264070684-en.

International Organization for Standardization (ISO). Biological evaluation of medical devices - Part 10: Tests for irritation and sensitization (ISO 10993-10). Geneva (CH): International Organization for Standardization (ISO); 1995.

FDA. International conference on harmonisation. Guidance on specific aspects of regulatory genotoxicity tests for pharmaceuticals. Fed Register. 1996;61(80):18197-18202.

OECD. Guidelines for the testing of chemicals. In vivo mammalian bone marrow cytogenetic test-chromosomal analysis (475). Paris (FR): OECD Publishing; 1993.

Kirkland DL. Genetic toxicology testing requirements: Official and unofficial views from Europe. Environ Mol Mutagen. 1993;21(1):8-14.

Aeschbscher HU. Rates of micronuclei induction in different mouse strains. Mutat Res. 1986;164:109-115.

Heddle J, Hite M, Salamone M. The induction of micronucleus, a measure of genotoxicity. Mutat Res. 1983;123:61-118.

Hart Y, Hartley A. Induction of micronucleus in the mouse. Mutat Res. 1983;120:127-132.

Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantification of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175:184-191.

Tice RR. The single cell gel/comet assay: a microgel electrophoretic technique for the detection of DNA damage and repair in individual cells. In: Philips DH, Venitt S. Environmental mutagenesis. Oxford (UK): Bios Scientific Publishers Ltd; 1994.

Moorhead PS. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res. 1960;23:613-616.

Chebotarev AN. A modified method of differential sister chromatid exchanges staining. B Exp Biol Med. 1978;85:243-244.

Fenech M, Morley AA. Measurement of micronuclei in lymphocytes. Mutat Res. 1985;147:28-36.

Wilson JG. Embryological considerations in teratology. Teratology principles and techniques. Chicago (IL): University of Chicago Press; 1965.

Dawson AB. A note on the staining of the skeleton of cleared specimens with alizarin red stain. Stain Tech. 1926;1:123-124.

Briggs GB, Oehme W. Toxicology. In: Baker JH, Russell LJ. The laboratory rat. Research applications. Volume II, Chapter 5. American College of Laboratory Animal Series. Orlando (FL): Academic Press Inc; 1980.

Chinedu E, Arome D, Ameh FS. A New method for determining acute toxicity in animal models. Toxicol Int. 2013;20(3):224-226.

Matsuzawa T, Nomura M, Unno T. Clinical pathology reference ranges of laboratory animals. J Vet Med Sci. 1993;55(3):351-362.

Stevens K, Mylecaine L. Issues in chronic toxicology. In: Hayes W. Principles and methods of toxicology. 3th ed. New York (NY): Raven Press; 1984. p. 273-319.

Suber R. Clinical pathology methods for toxicological studies. In: Hayes W. Principles and methods of toxicology. 3th ed. New York (NY): Raven Press; 1984. p. 729-762.

Jeklova E, Leva L, Knotigova P, Faldyna M. Age-related changes in selected haematology parameters in rabbits. Res Vet Sci. 2009;86:525-528.

Alemán CL, Noa M, Más R, Rodeiro I, Mesa R, Menéndez R, et al. Reference data for the principal physiological indicators in three species of laboratory animals. Lab Animals. 2000;34:379-385.

Coles EH. Veterinary Clinical Pathology. 4th ed. Philadelphia (PA): WB Saunders; 1986. 486 p. ISBN: 9780721618289.

Murray RK, Granner PA, Mayer PA, Rodwell VW. Harper's Biochemistry. 25th ed. New York (NY): McGraw-Hill; 2000. 927 p. ISBN: 9780838536902.

Petruška P, Kalafová A, Kolesárová A, Zbyňovská K, Latacz A, Capcarová M. Effect of quercetin on haematological parameters of rabbits: a gender comparison. JMBFS. 2013;2(Special issue 1):1540-1549.

Peterson ML, Smialowicz R, Harder S, Ketcham B, House D. The effect of controlled ozone exposure on human lymphocyte function. Environ Res. 1981;24:299-308.

Guyton AC, Hall JE. A textbook on medical physiology. 10th ed. Philadelphia (PA): W.B. Saunders Company; 2000. 1064 p. ISBN: 9780721686776.

Ganong WF. Review of medical physiology. 20th ed. New York (NY): McGraw Hill Lange; 2001. 870 p. ISBN: 9780838582824.

Díaz Llera S, González Y, Prieto EA, Azoy A. Genotoxic effect of ozone in human peripheral blood leukocytes. Mutat Res. 2002;517:13-20.

Duell TH, Lengfelder E, Fink R, Giesen R, Bauchinger M. Effect of activated oxygen species in human lymphocytes. Mutat Res. 1995;336:29-38.

Yu TW, Anserson D. Reactive oxygen species-induced DNA damage and its modification: a chemical investigation. Mutat Res. 1997;379:201-210.

Gyorgy SN, Young S. Sensitivity of pol A mutants of Escherichia coli k-12 to ozone and radiations. Mutagenesis. 1988;3(3):257-261.

Metka M, Enzelsberger H, Salzer H, Rokitansky A. Zur Frage der Teratogenität und Toxizität von medizinischem Ozon-ein Studie an trächtigen Ratten [On the issue of teratogenicity and toxicity of medical ozone-a study in pregnant rats]. OzoNachrichten. 1988;7:21-29.

Kavlock RJ, Daston G, Grabowski CT. Studies in the development toxicity of ozone: Prenatal effects. Toxicol Appl Pharmacol. 1979;48:19-28.

Kavlock RJ, Meyer E, Grabowski CT. Studies on the developmental toxicity of ozone: Postnatal effects. Toxicol Lett. 1980;5:3-9.

Bocci V. Tropospheric ozone toxicity vs. usefulness of ozone therapy. Arch Med Res. 2007;38:265-267.

Downloads

Published

2018-12-15

How to Cite

Menendez-Cepero, S., Zamora, Z., & Hernandez, F. (2018). Importance of the toxicological tests in the application and safety of ozone therapy. Journal of Ozone Therapy, 2(3). https://doi.org/10.7203/jo3t.2.3.2018.10009
Metrics
Views/Downloads
  • Abstract
    1021
  • PDF
    453

Issue

Section

Original Article

Metrics

Similar Articles

> >> 

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)

> >>