Ozone normally occurs in a gas state as three atoms of oxygen (O) linked in a cyclic structure and is a by-product of water purification, bleaching, and any process generating a spark or electric arc in the presence of oxygen. It is also found in the atmosphere, with higher altitudes containing higher levels of ozone. It is found in the stratosphere where it absorbs various ultraviolet radiation. Ozone is also an environmental air pollutant along with others such as sulfur dioxide and particulate matter. Ozone can react with air and create nitrogen dioxide, another air pollutant if it is improperly generated.
In spite of this, ozone can be generated by medical devices for therapeutic purposes. Potential medical applications of ozone therapy have a wide range including 1) limiting postoperative pain after dental extraction when used as a gel, 2) repairing inner ear damage caused by acoustic trauma, 3) reducing coronary stent restenosis when applied as an auto-hem-transfusion, and 4) enhancing methicillin-resistant Staphylococcus aureus elimination in mediastinitis when used in conjunction with antibiotics.
Outside of medicine, ozone has been proposed for use in various settings such as in the pretreatment of textile wastewater. While ozone itself can cause health troubles, it can also react with chemicals found in a multitude of products to lead to other potentially toxic substances such as formaldehyde. Despite proponents for its use and the potential applications, toxicity can occur even at environmental levels and may be related to cardiac, respiratory, and neurologic events.
With the wide range of possible applications and toxicity that can occur at environmental levels from within a home, research on ozone use and toxicity is likely to increase in the future.
Exposure to ozone is most likely unintended and due to environmental sources both indoor and outdoor. Indoor exposure is decreased in homes with central air, due to the decreased exchange of indoor and outdoor air and filtering performed by the air conditioning unit. Despite its decreased presence, ozone can react with numerous indoor chemicals such as those related to wood flooring, carpeting, and perfume to create potentially harmful compounds.
One's outside environment is a major determinant of ozone exposure, potential toxicity, and overall cardiovascular and respiratory mortality. One large study of 95 communities in the United States found a statistically significant association between increases in ozone measured in parts per billion (ppb) and short-term mortality. This study illustrates the widespread national public health concerns of ozone exposure. Countries outside of the United States, such as South Korea and Iceland, have also recognized the health impacts of ozone and the impact on public health.
The exact level and duration of ozone exposure that creates toxicity are not yet known. Additionally, humans may have variable sensitivity to ozone exposure. One study found that pediatric asthmatics might be more sensitive to certain air pollutants such as ozone. Another suggested that exposure to ambient levels of ozone may be enough to initiate inflammatory cascades of the respiratory tract. Noting that, and the study involving 95 communities, it is plausible to say that ozone toxicity affects everyone to some degree and is dependent on multiple factors within and outside of our control.
The exact risk of ozone toxicity is difficult to determine due to many factors. One large study suggested that a 10 ppb increase in ozone was associated with a 0.52% risk of non-injury-related daily mortality in that community the following week. Additionally, the same increase in environmental ozone may cause a 0.64% increase in mortality due to cardiovascular or respiratory causes.
Aside from the general ozone toxicity, it has the potential to be iatrogenic and work-related. Despite that potential, little research and no case reports were found.
Ozone is a potent oxidant that has the potential to be helpful or harmful like most other substances depending on the concentration, location, and duration of exposure. For example, ozone has shown to be beneficial in treating chronic limb ischemia and several kinds of skin infection. Conversely higher doses or more prolonged exposure to the skin will lead to progressive depletion of antioxidant content in the stratum corneum.
In discussing toxicokinetics, it may be helpful to differentiate the exposure location, as the skin is somewhat tolerant (although chronic contact can be deleterious), while the respiratory system is essentially intolerant and can show harmful effects even at low ambient environmental concentrations. Tissue effects can be considered on the basis of ozone’s specificity to certain compounds in addition to its low aqueous solubility and diffusibility. It is important to note that all possible pathways of injury are not yet known, and some known effects are not yet well understood.
Toxic effects are considered to occur through free radicals and oxidation, or through radical-dependent pathways. Aside from the generation of free radicals, ozone can deplete a tissue of specific compounds, such as antioxidants (tocopherols and ascorbate) in separate layers of skin (upper epidermis, lower epidermis, dermis). Additionally, there is a noted increase in lipid and protein oxidation showing oxidative stress. Longer exposure to increased concentrations has shown an increase in cyclooxygenase-2, which is a pro-inflammatory marker.
While effects are still related to oxidation and inflammatory pathways, the respiratory tract has some mediation through interleukin-8 and growth-related oncogene-α.
For most patients with symptoms related to ozone toxicity, history will be non-specific. Findings will likely depend on the bodily system involved, such as worsening respiratory symptoms in a patient with underlying asthma since this population is particularly susceptible to ozone effects. The specific history of present illness events may only be found in patients undergoing unconventional medical asthmatic therapies or individuals exposed in a work environment.
Symptoms themselves are largely related to the delivery method of exposure, concentration, and duration. Ozone has been delivered in many routes including, but not limited to, intravenous, intramuscular, topically, intra-articular, nasal, rectal, and oral.
Evaluation of ozone toxicity is similar to the evaluation of any pulmonary irritant. Oxygen saturation monitoring should be implemented and also bedside spirometry. Providers should also consider arterial blood gas analysis and chest radiography as potential exposure to other pulmonary irritants should always be considered. An electrocardiogram should be performed as well in patients with or at risk for the underlying cardiac disease.
No specific treatment is available for individuals exposed to ozone, though some have suggested that oral intake of Vitamin E is beneficial to the chronic ambient exposure most experience. Budesonide has been shown to inhibit the airway neutrophilic inflammatory response although it does not prevent functional impairment of the airway.
Providers should be aware of the use of ozone therapy by holistic practitioners and ozone therapists. Although shown to be safe there have been instances with inexperienced individuals using ozone improperly, potentially causing harm. As with any drug, there is a therapeutic window depending on the dosage. Unfortunately, there is a lack of financial support for conducting randomized controlled trials, and much remains to be discovered about both therapeutic and toxic effects of ozone.
The actual incidence of ozone toxicity remains unknown but in any case, healthcare providers, emergency room personnel, and nurse practitioners should be familiar with the presentation and management of ozone toxicity. In most cases, the toxicity occurs because of improper use of ozone. Because there is little known about the management of ozone toxicity one should apply the trauma ABCDE protocol and offer supportive care. Most patients do improve with corticosteroid/oxygen therapy.
|||Cavka A,Wallenius A,Alriksson B,Nilvebrant NO,Jönsson LJ, Ozone detoxification of steam-pretreated Norway spruce. Biotechnology for biofuels. 2015 [PubMed PMID: 26617671]|
|||Rowland FS, Stratospheric ozone depletion. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2006 May 29 [PubMed PMID: 16627294]|
|||Rivas FJ,Solís RR,Beltrán FJ,Gimeno O, Sunlight driven photolytic ozonation as an advanced oxidation process in the oxidation of bezafibrate, cotinine and iopamidol. Water research. 2018 Dec 21; [PubMed PMID: 30599282]|
|||Saad A,Elginoz N,Germirli Babuna F,Iskender G, Life cycle assessment of a large water treatment plant in Turkey. Environmental science and pollution research international. 2018 Nov 29; [PubMed PMID: 30499087]|
|||Poblete R,Oller I,Maldonado MI,Cortes E, Improved landfill leachate quality using ozone, UV solar radiation, hydrogen peroxide, persulfate and adsorption processes. Journal of environmental management. 2018 Nov 20; [PubMed PMID: 30468956]|
|||Elvis AM,Ekta JS, Ozone therapy: A clinical review. Journal of natural science, biology, and medicine. 2011 Jan; [PubMed PMID: 22470237]|
|||Buckey JC, Use of Gases to Treat Cochlear Conditions. Frontiers in cellular neuroscience. 2019; [PubMed PMID: 31068792]|
|||Onal M,Elsurer C,Selimoglu N,Yilmaz M,Erdogan E,Bengi Celik J,Kal O,Onal O, Ozone Prevents Cochlear Damage From Ischemia-Reperfusion Injury in Guinea Pigs. Artificial organs. 2017 Aug; [PubMed PMID: 28261890]|
|||Üreyen ÇM,Baş CY,Arslan Ş, Myocardial Infarction after Ozone Therapy: Is Ozone Therapy Dr. Jekyll or Mr. Hyde? Cardiology. 2015; [PubMed PMID: 26139204]|
|||Barone A,Otero-Losada M,Grangeat AM,Cao G,Azzato F,Rodríguez A,Milei J, Ozonetherapy protects from in-stent coronary neointimal proliferation. Role of redoxins. International journal of cardiology. 2016 Nov 15; [PubMed PMID: 27541668]|
|||Ofori I,Maddila S,Lin J,Jonnalagadda SB, Ozone initiated inactivation of Escherichia coli and Staphylococcus aureus in water: Influence of selected organic solvents prevalent in wastewaters. Chemosphere. 2018 Sep; [PubMed PMID: 29730564]|
|||Lu J,Li M,Huang J,Gao L,Pan Y,Fu Z,Dou J,Huang J,Xiang Y, [Effect of ozone on Staphylococcus aureus colonization in patients with atopic dermatitis]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences. 2018 Feb 28; [PubMed PMID: 29559599]|
|||Holkar CR,Jadhav AJ,Pinjari DV,Mahamuni NM,Pandit AB, A critical review on textile wastewater treatments: Possible approaches. Journal of environmental management. 2016 Nov 1 [PubMed PMID: 27497312]|
|||[PubMed PMID: 31279806]|
|||[PubMed PMID: 31004526]|
|||Chen H,Lin T,Chen W,Tao H,Xu H, Removal of disinfection byproduct precursors and reduction in additive toxicity of chlorinated and chloraminated waters by ozonation and up-flow biological activated carbon process. Chemosphere. 2019 Feb; [PubMed PMID: 30391883]|
|||Cheema WA,Andersen HR,Kaarsholm KMS, Improved DBP elimination from swimming pool water by continuous combined UV and ozone treatment. Water research. 2018 Dec 15; [PubMed PMID: 30312794]|
|||Weschler CJ, Ozone's impact on public health: contributions from indoor exposures to ozone and products of ozone-initiated chemistry. Environmental health perspectives. 2006 Oct [PubMed PMID: 17035131]|
|||Fryer AD,Jacoby DB,Wicher SA, Protective Role of Eosinophils and TNFa after Ozone Inhalation. Research report (Health Effects Institute). 2017 Mar; [PubMed PMID: 29659241]|
|||Jung SJ,Mehta JS,Tong L, Effects of environment pollution on the ocular surface. The ocular surface. 2018 Apr; [PubMed PMID: 29510225]|
|||Goodman JE,Zu K,Loftus CT,Lynch HN,Prueitt RL,Mohar I,Shubin SP,Sax SN, Short-term ozone exposure and asthma severity: Weight-of-evidence analysis. Environmental research. 2018 Jan; [PubMed PMID: 29059621]|
|||[PubMed PMID: 31254073]|
|||Schmelzer KR,Wheelock AM,Dettmer K,Morin D,Hammock BD, The role of inflammatory mediators in the synergistic toxicity of ozone and 1-nitronaphthalene in rat airways. Environmental health perspectives. 2006 Sep [PubMed PMID: 16966088]|
|||de Monte A,van der Zee H,Bocci V, Major ozonated autohemotherapy in chronic limb ischemia with ulcerations. Journal of alternative and complementary medicine (New York, N.Y.). 2005 Apr [PubMed PMID: 15865505]|
|||[PubMed PMID: 27336329]|
|||[PubMed PMID: 9013880]|
|||Hörl G,Ledinski G,Kager G,Hallström S,Tafeit E,Koestenberger M,Jürgens G,Cvirn G, In vitro oxidation of LDL by ozone. Chemistry and physics of lipids. 2014 Oct [PubMed PMID: 24835738]|
|||[PubMed PMID: 14661098]|
|||Martínez-Canabal A,Angoa-Pérez M,Rugerio-Vargas C,Borgonio-Perez G,Rivas-Arancibia S, Effect of growth hormone on Cyclooxygenase-2 expression in the hippocampus of rats chronically exposed to ozone. The International journal of neuroscience. 2008 Mar [PubMed PMID: 18300015]|
|||Li X,Chen Q,Zheng X,Li Y,Han M,Liu T,Xiao J,Guo L,Zeng W,Zhang J,Ma W, Effects of ambient ozone concentrations with different averaging times on asthma exacerbations: A meta-analysis. The Science of the total environment. 2019 Nov 15 [PubMed PMID: 31325855]|
|||[PubMed PMID: 28624471]|
|||Pryor WA, Can vitamin E protect humans against the pathological effects of ozone in smog? The American journal of clinical nutrition. 1991 Mar [PubMed PMID: 2000826]|
|||[PubMed PMID: 28584201]|
|||[PubMed PMID: 11751182]|