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OZONE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Ozone is a highly reactive trioxygen compound produced both naturally in the stratosphere and artificially as a chemical reagent. Medical ozone (O3) gas is used to disinfect and treat diseases (eg, infected wounds, circulatory disorders, macular degeneration, rheumatism/arthritis) by inactivating bacteria, viruses, fungi, yeast and protozoa, and stimulating oxygen metabolism, and activating the immune system.

Specific Substances

    1) Ozone
    2) Triatomic oxygen
    3) CAS 10028-15-6
    4) Molecular Formula: O3
    5) OXYGEN, MOL (O3)
    1.2.1) MOLECULAR FORMULA
    1) O3

Available Forms Sources

    A) FORMS
    1) Under ambient conditions ozone is a colorless to bluish gas with a characteristic, pleasant odor in concentrations of less than 2 ppm (Budavari, 1989; Lewis, 1993).
    2) Between minus 169.6 degrees F (minus 111.9 degrees C) and minus 314 degrees F (minus 192.7 degrees C), ozone is a dark blue liquid. Below minus 314 degrees F (minus 192.7 degrees C), it exists as blue-black crystals (EPA, 1985).
    B) SOURCES
    1) NATURAL: Produced by ultraviolet light action on oxygen. Maximum concentration occurs in the atmosphere at around 75,000 feet. Natural electrical discharges (such as lightning) also produce ozone (Beard, 1982).
    2) Ozone is also formed in photochemical reactions between nitrogen oxides and hydrocarbon emissions from cars and trucks (HSDB , 1996).
    3) Ozone occurs primarily outdoors (Speizer, 1985).
    4) The concentration of ozone in air may vary. It occurs at approximately 0.05 ppm at sea level (HSDB , 1996).
    a) Concentrations in urban air are higher. Levels can reach 0.5 ppm in urban photochemical smog (WHO, 1979), higher than the ACGIH-TLV and OSHA PEL.
    b) Seasonal fluctuations occur, with levels being highest in the summer and lowest in the winter (Bates, 1989; Lioy & Dyba, 1989).
    c) Fluctuations also occur in urban areas during the day; highest concentrations occur near mid-day or early afternoon (Lioy & Dyba, 1989).
    d) Motor vehicle exhaust is seen to exhibit the highest photochemical ozone creation potential (POCP) of all hydrocarbon emissions tested (Derwent et al, 1996).
    5) These daily, seasonal, and geographic fluctuations of ozone concentration should be taken into account in designing an appropriate monitoring scheme and work shift for occupational exposures, especially for persons working outdoors.
    6) Arc welding shielded by inert gases such as argon and helium room air ozonizers, office photocopying machines, fumigation chambers, high voltage electrical apparatus, UV quartz lamps, and ozonizers for treatment of sewage (Jaffe, 1967) 1968).
    7) Ozone has been measured at concentrations as high as 0.56 ppm in laser printer exhaust (HSDB , 1996).
    8) The most likely sources of exposures to ozone in industry are leakage from ozone-using processes and high voltage electrical equipment and from electric arc welding. (The latter is more potently a sources of nitrogen oxides.) Aircraft flying at altitudes greater than 33,000 ft may take significant quantities of atmospheric ozone into their cabin ventilation (Beard, 1982).
    9) FOOD TREATMENT: A study was done to examine the solubility and stability of ozone in shrimp-meat extract (SME) and the bacteriocidal effect of ozone on shrimp-meat microorganisms. Ozone produced a decomposition rate of 2.7%/min in the SME from a saturated solution (1.4 mg O3/L) at 5 and 25 degrees C. Nine bacterial strains were tested and Salmonella typhimurium was found to be the most resistant to ozone. No mutagen was observed in shrimp meat when it was ozonated in saline (Chen et al, 1992).
    10) DECOMPOSITION OF 2,4-D: A laboratory study was conducted to determine the rate constants for degradation of herbicides by ozone. The half-life for removal of 2,4-D at pH 7.5 and in the presence of bicarbonate ions was 39.5 minutes at a dissolved ozone concentration of 10 micromolar. The addition of a second herbicide did not affect the relative degradation rate (Xiong & Graham, 1992).
    C) USES
    1) Ozone is used as a disinfectant and bleaching agent, in the manufacture of ink, as a catalyst, in water treatment, and as an inhibitor of mold and bacteria (EPA, 1985).
    2) Ozone is used as a disinfectant for air and water by virtue of its oxidizing power; for bleaching waxes, textiles, and oils; and in organic syntheses. It forms ozonides which are sometimes useful oxidizing compounds (Budavari, 1989; Lewis, 1993).
    3) OZONE THERAPY: Medical ozone (O3) gas is used to disinfect and treat diseases (eg, infected wounds, circulatory disorders, macular degeneration, rheumatism/arthritis) by inactivating bacteria, viruses, fungi, yeast and protozoa, and stimulating oxygen metabolism, and activating the immune system (Elvis & Ekta, 2011). Intraarticular ozone infiltrations in 2 patients resulted in cortical blindness and seizures (Rolan et al, 2012). In dental medicine, the ozonized water is used as a spray or compress (Elvis & Ekta, 2011).
    4) WATER TREATMENT
    a) Ozone has been used for more than 80 years, primarily for disinfection of municipal drinking water (Freeman, 1989).
    b) The first water treatment plants using ozone were installed in the US in the 1940s. The first wastewater plant to use ozone for disinfection was operated in 1973 (Freeman, 1989).
    c) Ozone treatment at more than 1.0 mg of TROs per L for several minutes efficiently disinfects seawater for mariculture applications (Sugita et al, 1992).
    d) A continuous flow laboratory reactor was constructed to investigate the decomposition of ozone to produce hydroxyl radicals that oxidize micropollutants in water. The reactor had a flow rate of 34 mL/min and the residence time could be varied between 1.4 to 27 seconds so that relatively short term effects could be monitored. Radical formation was found to be a function of the chemical composition of the water in natural systems (Guittonneau et al, 1992).
    e) In a study of the design of a new ozone contactor (the deep U tube), laboratory and modeling data were compared to experimental data from a full-scale plant and a pilot plant. The results showed the deep U tube reactor to be more efficient than the stirred tank reactor design and close to the plug flow reactor in performance (Roustan et al, 1992).
    f) A study was done to evaluate the kinetic parameters for the ozonation of wastewaters from a distillery and a tomato processing plant (Beltran et al, 1992).
    g) The evolution of organic and inorganic matter, as a function of ozonation time, was followed by monitoring the chemical oxygen demand.
    h) The early (faster rate) stage was dominated by gas-liquid reaction and the later stages by bulk solution reactions, particularly for the tomato wastewaters.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Ozone is a skin, eye, upper respiratory tract, and mucous membrane irritant. The primary symptoms after acute exposure are irritation of the eyes, nose, throat, and chest, as well as fatigue. Exposure to less than 0.5 ppm may produce symptoms and alter pulmonary function tests, but does not significantly decrease exercise potential.
    B) The primary site of acute injury is the lung; injury is characterized by pulmonary congestion, edema, and hemorrhage.
    C) Human systemic effects by inhalation: visual field changes, lacrimation, headache, decreased pulse rate, decreased blood pressure, dermatitis, cough, dyspnea, respiratory stimulation, and other pulmonary changes.
    D) Ozone increases bronchial allergen responses in subjects with allergic asthma or rhinitis.
    E) The toxicity of ozone is increased by its interaction with other environmental oxidants.
    F) OZONE THERAPY: Intraarticular ozone infiltrations in 2 patients resulted in cortical blindness and seizures.
    0.2.3) VITAL SIGNS
    A) Decreased pulse rate and blood pressure may occur in humans after inhalation.
    0.2.4) HEENT
    A) Conjunctivitis has been reported. Levels of 2 ppm for 2 hours produced throat and mouth dryness.
    0.2.5) CARDIOVASCULAR
    A) Cardiovascular effects reported have been secondary to respiratory changes.
    0.2.6) RESPIRATORY
    A) Both human and animals have increased respiratory rate and shallow breathing which decreases 30 minutes after exposure. The maximum effects may be seen 12 to 24 hours later. Severe pulmonary symptoms reported by some authors include edema, hemorrhage, bronchopneumonia, exertional dyspnea, bronchitis and bronchiolitis.
    0.2.7) NEUROLOGIC
    A) Drowsiness, dizziness, headache and fatigue have been reported after industrial exposure.
    0.2.8) GASTROINTESTINAL
    A) Anorexia, nausea and vomiting have been seen.
    0.2.9) HEPATIC
    A) Compounds generated by ozone (not ozone itself) have been implicated in animal hepatic damage. This has not been seen in humans.
    0.2.13) HEMATOLOGIC
    A) In vivo exposures of RBCs to ozone changed their shapes and made them more susceptible to hemolysis. Oxygen carrying capacity appears to be unchanged.
    0.2.14) DERMATOLOGIC
    A) Severe burns can occur from direct contact with the cryogenic liquid or with escaping compressed gas.
    0.2.17) METABOLISM
    A) Enzymatic alterations were observed.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no studies were found on the possible reproductive effects of ozone in humans. Some abnormalities have been seen in mice exposed prenatally. Teratogenic effects were observed in rat experiments.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no studies were found on the potential carcinogenicity of ozone in humans.
    0.2.22) OTHER
    A) There is some evidence that humans may develop a tolerance to the effects of low concentrations.

Laboratory Monitoring

    A) Ozone reacts quickly with cellular tissues, and ozone is not found in the blood or serum.
    B) Induction of the glutathione perioxidase system is one of the most sensitive measures of ozone exposure.

Treatment Overview

    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) Patients with sweating, cough and collapse had symptoms relieved with oxygen therapy and all symptoms disappeared within 2 days.
    C) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    D) Other treatment is supportive and directed at maintaining adequate pulmonary function. Systemic toxicity due to industrial ozone exposure has not been reported.
    E) VITAMIN E (DIETARY) - Direct evidence for a protective action against peroxidation of unsaturated fatty acids is lacking in humans.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Escaping compressed gas may cause frostbite. Therapy involves rapid rewarming at a temperature of 42 degrees Centigrade as soon as it is available. The use of a variety of phamacologic agents to help restore perfusion to the tissues is controversial. Surgical intervention is limited to the late stages of healing unless obvious gangrenous tissue is present earlier. Non-pharmacologic therapy is used to treat the frostbite.

Range Of Toxicity

    A) Damage has occurred at concentrations as low as 0.5 ppm for 2 hours of exposure.
    B) Patchy damage of the ciliated cells of the upper airway may be seen after exposure to 0.2 to 0.5 ppm for 7 days, 8 to 24 hours per day, in various experimental animal species.

Clinical Effects

Summary Of Exposure

    A) Ozone is a skin, eye, upper respiratory tract, and mucous membrane irritant. The primary symptoms after acute exposure are irritation of the eyes, nose, throat, and chest, as well as fatigue. Exposure to less than 0.5 ppm may produce symptoms and alter pulmonary function tests, but does not significantly decrease exercise potential.
    B) The primary site of acute injury is the lung; injury is characterized by pulmonary congestion, edema, and hemorrhage.
    C) Human systemic effects by inhalation: visual field changes, lacrimation, headache, decreased pulse rate, decreased blood pressure, dermatitis, cough, dyspnea, respiratory stimulation, and other pulmonary changes.
    D) Ozone increases bronchial allergen responses in subjects with allergic asthma or rhinitis.
    E) The toxicity of ozone is increased by its interaction with other environmental oxidants.
    F) OZONE THERAPY: Intraarticular ozone infiltrations in 2 patients resulted in cortical blindness and seizures.

Vital Signs

    3.3.1) SUMMARY
    A) Decreased pulse rate and blood pressure may occur in humans after inhalation.
    3.3.4) BLOOD PRESSURE
    A) Decreased blood pressure may occur in humans after inhalation (Sax & Lewis, 1992).
    3.3.5) PULSE
    A) Decreased pulse rate may occur in humans after inhalation (Sax & Lewis, 1992).

Heent

    3.4.1) SUMMARY
    A) Conjunctivitis has been reported. Levels of 2 ppm for 2 hours produced throat and mouth dryness.
    3.4.3) EYES
    A) CONJUNCTIVITIS: Ozone is a powerful oxidizer which may cause ocular irritation.
    B) IRRITATION: Ozone induced eye irritation in the rabbit in the Standard Draize Test (RTECS , 1991).
    C) INTRAARTICULAR OZONE THERAPY: Intraarticular ozone infiltrations in 2 patients resulted in cortical blindness and seizures.
    1) CASE REPORT: A 75-year-old man developed dizziness, slurred speech, left central facial paralysis, cortical blindness, and tingling, numbness with mild weakness of the left extremities 10 minutes after receiving a paravertebral ozone therapy session and autohemotherapy for spondylarthrosis. A brain MRI revealed subcortical/juxtacortical white matter chronic ischemic lesions in the right cerebral hemisphere without evidence of acute lesions. There was stenosis of the distal branch of the left cerebral posterior artery and a severe stenosis of the right carotid artery on MR angiograms. Bilateral hypoperfusion areas particularly in the left occipitotemporal region were observed by a 99mTc-ECD brain SPECT. The next day, he developed visual hallucinations, various episodes of forced oculocephalic deviation to the left, clonus on left extremities, and a tonic-clonic seizure. He recovered following supportive care, including treatment with valproic acid and levetiracetam. On day 7, another brain MRI scan revealed one small juxtacortical subacute ischemic lesion in the right occipital lobe (Rolan et al, 2012).
    2) CASE REPORT: A 60-year-old woman developed posterior cortical blindness and tonic-clonic seizure briefly after intraarticular infiltration of ozone and procaine for the treatment of a left should joint disease. On presentation, she was disoriented with repetitive speech, anterograde memory impairment and cortical blindness. A right acute ischemic cerebellar lesion was observed on a brain MRI scan. Following levetiracetam therapy, her condition resolved. A cerebellar ischemic lesion was observed in another MRI scan (Rolan et al, 2012).
    3.4.6) THROAT
    A) Levels of 2 ppm for 2 hours produced throat and mouth dryness (Griswald et al, 1957).

Cardiovascular

    3.5.1) SUMMARY
    A) Cardiovascular effects reported have been secondary to respiratory changes.
    3.5.2) CLINICAL EFFECTS
    A) CARDIOVASCULAR FINDING
    1) Little toxicity has been attributed to ozone itself. Cardiovascular effects reported have been secondary to respiratory changes (Menzel, 1984).

Respiratory

    3.6.1) SUMMARY
    A) Both human and animals have increased respiratory rate and shallow breathing which decreases 30 minutes after exposure. The maximum effects may be seen 12 to 24 hours later. Severe pulmonary symptoms reported by some authors include edema, hemorrhage, bronchopneumonia, exertional dyspnea, bronchitis and bronchiolitis.
    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY FAILURE
    1) Humans develop ozone-related increases in pulmonary resistance following administration of histamine, methacholine or acetylcholine (Holtzman et al, 1979; Menzel, 1984). The minimally effective concentration is estimated at being 0.2 to 0.4 ppm for 10 to 30 minutes (Menzel, 1984).
    2) Both humans and animals have increased respiratory rate and shallow breathing, which decreases 30 minutes after exposure. The maximum effect is 12 to 24 hours later (Menzel, 1984).
    3) A characteristic centriacinar lesion is seen in humans. No specific concentration/anticipated damage effect is known (Menzel, 1984).
    4) Severe pulmonary symptoms reported by other authors include edema, bronchopneumonia, exertional dyspnea (Kleinfield, 1975), bronchitis and bronchiolitis (Jaffe, 1967) 1968) and hemorrhage (Scheel et al, 1959).
    5) Nose versus mouth breathing made no difference in pulmonary function in a study on 17 healthy nonsmoking volunteers exposed to 0.4 ppm ozone for 30 minutes while exercising (Hynes et al, 1988).
    6) Hyperresponsiveness from an acute exposure may persist for some time. Reductions in FVC, FEV(1.0) and FEV (3.0) were greater after a second exposure to 0.45 ppm ozone than from an initial exposure 2 days earlier. Therefore the acute respiratory effects of ozone persist for at least 48 hours (Bedi et al, 1985). In another study the hyperresponsiveness was apparent within 12 hours after an initial exposure to 0.25 ppm ozone but had disappeared by 72 hours (Folinsbee & Horvath, 1986).
    7) ADAPTATION :Repeated exposures under controlled conditions produce a diminished response to ozone, called adaptation, by the fourth day of exposure (Folinsbee et al, 1983).
    a) Whether or not an individual responds to ozone is consistent during different seasons of the year, when ambient ozone concentrations vary. Responders had lost much of their response by fall, toward the end of the period of high ambient ozone levels, but regained their responsiveness by the following spring (Linn et al, 1988).
    8) Individuals with allergic rhinitis were no more sensitive to ozone than normal subjects when exposed to 0.18 ppm (McDonnell et al, 1987).
    9) Healthy persons engaged in light exercise are likely to experience chest discomfort and cough, and to show measurable impairment of expiratory pulmonary functions when exposed for 2 hours or less to ozone concentrations lower than 0.37 ppm. Some persons who appear healthy show significant responses to 1 hour exposures of 0.15 ppm or less, with light exercise. Heavier exercise increases the responses materially (Beard, 1982).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RESPIRATORY INSUFFICIENCY
    a) INFLAMMATION :Necrosis is a commonly reported sign in animal exposures. Inflammation is seen in all species, but the degree varies considerably (Menzel, 1984).
    b) BELOW 1 PPM - Damage is primarily to the junction of the alveoli and connecting air passages (Menzel, 1984).
    c) Type 1 pneumocytes are killed at concentrations of 0.8 ppm for 12 hours (Castleman et al, 1980).
    d) Proliferation of Type 2 pneumocytes is a classic sign of ozone toxicity, regardless of species (Menzel, 1984).
    e) Rapid, shallow breathing occurs in both humans and animals after exposures of as little as 0.26 ppm for 2 hours (Amdur et al, 1978). Maximum effects are often delayed 1 day after exposure (Menzel, 1984).
    f) Ozone appears associated with an increased susceptibility to infections in animals (Gardner, 1982). Increased human susceptibility due to ambient air ozone concentrations has not been shown (Menzel, 1984).
    g) Very short, high exposures (0.5 ppm for 5 minutes) were sufficient to induce increases in pulmonary resistance in baboons. Cromolyn sodium significantly prevented the increase but did not affect respiratory mechanics during control periods. These results suggest that ozone affects the surface epithelial cells (Fouke et al, 1988).
    h) The lesions were more abundant and more severe in rats which had been exposed to ozone during exercise than during rest. The increased effect was greater than predicted from the estimated effective dose (Mautz et al, 1985).

Neurologic

    3.7.1) SUMMARY
    A) Drowsiness, dizziness, headache and fatigue have been reported after industrial exposure.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Drowsiness, dizziness and fatigue have been reported by various authors after industrial exposures (Finkel, 1983; Anon, 1975). Substantiating evidence for extensive central nervous system depression has not been shown experimentally (Beard, 1982).
    B) HEADACHE
    1) Headaches have been reported in industrial exposures (Kleinfield et al, 1975).
    C) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) INTRAARTICULAR OZONE THERAPY: Intraarticular ozone infiltrations in 2 patients resulted in cortical blindness and seizures.
    1) CASE REPORT: A 75-year-old man developed dizziness, slurred speech, left central facial paralysis, cortical blindness, and tingling, numbness with mild weakness of the left extremities 10 minutes after receiving a paravertebral ozone therapy session and autohemotherapy for spondylarthrosis. A brain MRI revealed subcortical/juxtacortical white matter chronic ischemic lesions in the right cerebral hemisphere without evidence of acute lesions. There was stenosis of the distal branch of the left cerebral posterior artery and a severe stenosis of the right carotid artery on MR angiograms. Bilateral hypoperfusion areas particularly in the left occipitotemporal region were observed by a 99mTc-ECD brain SPECT. The next day, he developed visual hallucinations, various episodes of forced oculocephalic deviation to the left, clonus on left extremities, and a tonic-clonic seizure. He recovered following supportive care, including treatment with valproic acid and levetiracetam. On day 7, another brain MRI scan revealed one small juxtacortical subacute ischemic lesion in the right occipital lobe (Rolan et al, 2012).
    2) CASE REPORT: A 60-year-old woman developed posterior cortical blindness and tonic-clonic seizure briefly after intraarticular infiltration of ozone and procaine for the treatment of a left should joint disease. On presentation, she was disoriented with repetitive speech, anterograde memory impairment and cortical blindness. A right acute ischemic cerebellar lesion was observed on a brain MRI scan. Following levetiracetam therapy, her condition resolved. A cerebellar ischemic lesion was observed in another MRI scan (Rolan et al, 2012).

Gastrointestinal

    3.8.1) SUMMARY
    A) Anorexia, nausea and vomiting have been seen.
    3.8.2) CLINICAL EFFECTS
    A) GASTRITIS
    1) Anorexia, nausea and vomiting have been reported (Anon, 1975).

Hepatic

    3.9.1) SUMMARY
    A) Compounds generated by ozone (not ozone itself) have been implicated in animal hepatic damage. This has not been seen in humans.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) Compounds generated by ozone (not the ozone itself) have been implicated in animal hepatic damage. This has not been seen in humans (Menzel, 1984).

Hematologic

    3.13.1) SUMMARY
    A) In vivo exposures of RBCs to ozone changed their shapes and made them more susceptible to hemolysis. Oxygen carrying capacity appears to be unchanged.
    3.13.2) CLINICAL EFFECTS
    A) ERYTHROCYTE ENZYME DEFICIENCY
    1) Decreases in RBC GSH content (Menzel, 1975) is seen in humans after exposure to 0.2 ppm for 30 to 60 minutes.
    2) RBC acetylcholinesterase decreases were seen in humans (Buckley et al, 1975) after exposure of 2 to 5 hours at 0.5 to 0.75 ppm.
    3) In vivo exposures of RBCs to ozone changes their shape from disc-like to spherical. They may be hemolyzed more easily. Oxygen carrying capacity appears unchanged (Beard, 1982).
    4) Inhibition of oxygen dissociation from oxyhemoglobin may occur at the tissue level (ACGIH, 1986).

Dermatologic

    3.14.1) SUMMARY
    A) Severe burns can occur from direct contact with the cryogenic liquid or with escaping compressed gas.
    3.14.2) CLINICAL EFFECTS
    A) FROSTBITE
    1) Frostbite and/or severe burns can occur from direct contact with the cryogenic liquid or with escaping gas (HSDB , 1990).

Immunologic

    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IMMUNE SYSTEM DISORDER
    a) Immunosuppression has been reported in guinea pigs and mice with chronic low exposures (Menzel, 1984). This effect has not been noted in humans.

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no studies were found on the possible reproductive effects of ozone in humans. Some abnormalities have been seen in mice exposed prenatally. Teratogenic effects were observed in rat experiments.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) Fetotoxicity, musculoskeletal system developmental abnormalities, and newborn behavioral and physical effects have been observed in experimental animals (RTECS, 1996; (HSDB , 1996).
    2) Exposure to 0.2 ppm to 1 ppm caused neurobehavioral abnormalities in mice (Kavlock et al, 1980) 1981). Subtle but persistent neurobehavioral effects have been reported by another research group in CD-1 mice following intrauterine exposure via maternal inhalation of ozone at 0.4 to 1.2 ppm (Dell'Omo et al, 1995a; Dell'Omo et al, 1995b; Petruzzi et al, 1995; Bignami et al, 1994). These effects are controversial and are difficult to extrapolate to humans.
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) Pre-implantation mortality was observed in rat experiments (RTECS, 1996). Increased neonatal mortality has been noted in mice (HSDB , 1996).
    2) In rats, pulmonary injury from ozone is much more severe in the pregnant or lactating animal than in virgin or post-lactation controls (Gunnison & Finkelstein, 1997). The significance of this affect for humans is unknown.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS10028-15-6 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no studies were found on the potential carcinogenicity of ozone in humans.
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) In mouse studies, ozone was found to be an equivocal tumorigenic agent and neoplastic by RTECS criteria with lung, thorax or respiration tumors (RTECS, 1996).
    2) Ozone produced pulmonary tumors in mice (but not in rats) and was not co-carcinogenic with NNK (an experimental nitrosamine compound) in either species (Boorman et al, 1995).

Genotoxicity

    A) Ozone is radiomimetic; mutations and chromosome aberrations have been produced at high concentrations.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Ozone reacts quickly with cellular tissues, and ozone is not found in the blood or serum.
    B) Induction of the glutathione perioxidase system is one of the most sensitive measures of ozone exposure.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Ozone reacts quickly with cellular tissues, and is not found in the blood or serum.
    2) Induction of the glutathione peroxidase system is one of the most sensitive measures of ozone exposure (Chow et al, 1981).
    3) Leakage of lactate dehydrogenase into the blood is reported as an indicator of increased lung permeability due to ozone-induced lung damage (Chow et al, 1977).

Methods

    A) SPECTROSCOPY/SPECTROMETRY
    1) Ozone can be measured directly in air by a Kruger UV photometer (HSDB , 1990).
    2) There is a NIOSH Analytical Method for determining ozone in air in the range of 0.1 to 0.4 mg/m(3). It is based on formation of a yellow color with alkaline potassium iodide with spectroscopy at 352 nm (HSDB , 1990).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Ozone reacts quickly with cellular tissues, and ozone is not found in the blood or serum.
    B) Induction of the glutathione perioxidase system is one of the most sensitive measures of ozone exposure.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) OXYGEN
    1) Patients with sweating, cough and collapse had symptoms relieved with oxygen therapy and all symptoms disappeared within 2 days.
    B) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    C) SUPPORT
    1) Other treatment is supportive and directed at maintaining adequate pulmonary function. Systemic toxicity due to industrial ozone exposure has not been reported.
    D) EXPERIMENTAL THERAPY
    1) Vitamin E has protected ANIMALS against the effects of ozone (Roehm et al, 1971) 1972). Direct evidence for a protective action against peroxidation of unsaturated fatty acid is lacking in humans (Menzel, 1984). Vitamin E appears to alter the rate and extent of the damage, but does not change the morphological damage (Menzel, 1984). One experiment where 18,000 international units of vitamin E were tested in 11 young men exposed to 0.5 parts per million while exercising, showed no protective value (Beard, 1982). Other antioxidants or free radical scavengers have not been shown to have protective effect in humans.
    2) Cromolyn sodium significantly prevented the increase in pulmonary resistance but did not affect respiratory mechanics during control periods in baboons (Fouke et al, 1988).

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.2) TREATMENT
    A) FROSTBITE
    1) PREHOSPITAL
    a) Rewarming of a localized area should only be considered if the risk of refreezing is unlikely. Avoid rubbing the frozen area which may cause further damage to the area (Grieve et al, 2011; Hallam et al, 2010).
    2) REWARMING
    a) Do not institute rewarming unless complete rewarming can be assured; refreezing thawed tissue increases tissue damage. Place affected area in a water bath with a temperature of 40 to 42 degrees Celsius for 15 to 30 minutes until thawing is complete. The bath should be large enough to permit complete immersion of the injured part, avoiding contact with the sides of the bath. A whirlpool bath would be ideal. Some authors suggest a mild antibacterial (ie, chlorhexidine, hexachlorophene or povidone-iodine) be added to the bath water. Tissues should be thoroughly rewarmed and pliable; the skin will appear a red-purple color (Grieve et al, 2011; Hallam et al, 2010; Murphy et al, 2000).
    b) Correct systemic hypothermia which can cause cold diuresis due to suppression of antidiuretic hormone; consider IV fluids (Grieve et al, 2011).
    c) Rewarming may be associated with increasing acute pain, requiring narcotic analgesics.
    d) For severe frostbite, clinical trials have shown that pentoxifylline, a phosphodiesterase inhibitor, can enhance tissue viability by increasing blood flow and reducing platelet activity (Hallam et al, 2010).
    3) WOUND CARE
    a) Digits should be separated by sterile absorbent cotton; no constrictive dressings should be used. Protective dressings should be changed twice per day.
    b) Perform twice daily hydrotherapy for 30 to 45 minutes in warm water at 40 degrees Celsius. This helps debride devitalized tissue and maintain range of motion. Keep the area warm and dry between treatments (Hallam et al, 2010; Murphy et al, 2000).
    c) The injured extremities should be elevated and should not be allowed to bear weight.
    d) In patients at risk for infection of necrotic tissue, prophylactic antibiotics and tetanus toxoid have been recommended by some authors (Hallam et al, 2010; Murphy et al, 2000).
    e) Non-tense clear blisters should be left intact due to the risk of infection; tense or hemorrhagic blisters may be carefully aspirated in a setting where aseptic technique is provided (Hallam et al, 2010).
    f) Further surgical debridement should be delayed until mummification demarcation has occurred (60 to 90 days). Spontaneous amputation may occur.
    g) Analgesics may be required during the rewarming phase; however, patients with severe pain should be evaluated for vasospasm.
    h) IMAGING: Arteriography and noninvasive vascular techniques (e.g., plain radiography, laser Doppler studies, digital plethysmography, infrared thermography, isotope scanning), have been useful in evaluating the extent of vasospasm after thawing and assessing whether debridement is needed (Hallam et al, 2010). In cases of severe frostbite, Technetium 99 (triple phase scanning) and MRI angiography have been shown to be the most useful to assess injury and determine the extent or need for surgical debridement (Hallam et al, 2010).
    i) TOPICAL THERAPY: Topical aloe vera may decrease tissue destruction and should be applied every 6 hours (Murphy et al, 2000).
    j) IBUPROFEN THERAPY: Ibuprofen, a thromboxane inhibitor, may help limit inflammatory damage and reduce tissue loss (Grieve et al, 2011; Murphy et al, 2000). DOSE: 400 mg orally every 12 hours is recommended (Hallam et al, 2010).
    k) THROMBOLYTIC THERAPY: Thrombolysis (intra-arterial or intravenous thrombolytic agents) may be beneficial in those patients at risk to lose a digit or a limb, if done within the first 24 hours of exposure. The use of tissue plasminogen activator (t-PA) to clear microvascular thromboses can restore arterial blood flow, but should be accompanied by close monitoring including angiography or technetium scanning to evaluate the injury and to evaluate the effects of t-PA administration. Potential risk of the procedure includes significant tissue edema that can lead to a rise in interstitial pressures resulting in compartment syndrome (Grieve et al, 2011).
    l) CONTROVERSIAL: Adjunct pharmacological agents (ie, heparin, vasodilators, prostacyclins, prostaglandin synthetase inhibitors, dextran) are controversial and not routinely recommended. The role of hyperbaric oxygen therapy, sympathectomy remains unclear (Grieve et al, 2011).
    m) CHRONIC PAIN: Vasomotor dysfunction can produce chronic pain. Amitriptyline has been used in some patients; some patients may need a referral for pain management. Inability to tolerate the cold (in the affected area) has been observed following a single episode of frostbite (Hallam et al, 2010).
    n) MORBIDITIES: Frostbite can produce localized osteoporosis and possible bone loss following a severe case. These events may take a year or more to develop. Children may be at greater risk to develop more severe events (ie, early arthritis) (Hallam et al, 2010).

Range Of Toxicity

Summary

    A) Damage has occurred at concentrations as low as 0.5 ppm for 2 hours of exposure.
    B) Patchy damage of the ciliated cells of the upper airway may be seen after exposure to 0.2 to 0.5 ppm for 7 days, 8 to 24 hours per day, in various experimental animal species.

Minimum Lethal Exposure

    A) CONCENTRATION LEVEL
    1) The lowest published lethal concentration via inhalation in humans is 50 ppm for 30 minutes (RTECS, 1996).
    2) Damage has occurred at concentrations as low as 0.5 ppm for 2 hours of exposure (Stephens et al, 1974).
    3) Type 1 pneumocytes may be killed at 0.8 ppm for 12 hours of exposure.
    4) Clara cell damage occurs at 0.5 to 0.8 ppm for 90 to 180 days of 8 hours per day exposure (Boorman et al, 1980).
    5) Patchy damage of the ciliated cells of the upper airway may be seen after exposures to 0.2 to 0.5 ppm for 7 days, 8 to 24 hours per day, in various experimental animal species (Menzel, 1984).

Maximum Tolerated Exposure

    A) CONCENTRATION LEVEL
    1) The actual concentration at which ozone exerts toxic effects in any individual depends on many factors, including morphology of the airway passage, age, sex, dietary and hormonal status, pre-existing disease states such as asthma, and capacity of cellular protective systems based on superoxide dismutase, glutathion peroxidase, and catalase (Mehlman & Borek, 1987; Clayton & Clayton, 1994).
    2) The extent of lung damage is generally a function of concentration of ozone rather than duration of exposure (Stephens et al, 1974b).
    3) Heavy exercise increases sensitivity to ozone for forced respiratory function (Goldstein et al, 1985).
    4) In one study, repeated exposure to 0.2 ppm ozone did not produce cumulative effects on respiratory function, exposure to 0.35 ppm produced greater decrements in FEV on day 3, but not days 4 and 5 of exposure, and effects were greater with 0.5 ppm, but were not present by the fourth day of exposure. The authors concluded that the respiratory effects of short-term exposure to ozone are cumulative, but that a period of adaptation follows after a few days of exposure. The adaptation involves not only improvement in pulmonary function, but also fewer subjective complaints (Folinsbee et al, 1980).
    5) Effects of Ozone in Humans - Occupational Exposures (Beard, 1982) -
    lZONE CONCENTRATION (ppm)SUBJECTIVE COMPLAINTS
    0.25None
    0.3 to 0.8Throat irritation
    0.9 peakThroat irritation Lassitude, headache
    0.8 to 1.7Dry mouth and throat Irritation of nose and eyes Chest tightness
    0.47Mucosal irritation
    0.94Severe mucosal irritation sleepiness
    Greater than 0.94Pulse increase, Sleepiness Headache
    0.1 to 0.6Substernal pain, Cough, Mucous membrane irritation

Workplace Standards

    A) ACGIH TLV Values for CAS10028-15-6 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Ozone, heavy work
    a) TLV:
    1) TLV-TWA: 0.05 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Not Listed
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    c) TLV Basis - Critical Effect(s): Pulm func
    d) Molecular Weight: 48
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:
    b) Adopted Value
    1) Ozone, light work
    a) TLV:
    1) TLV-TWA: 0.1 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Not Listed
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    c) TLV Basis - Critical Effect(s): Pulm func
    d) Molecular Weight: 48
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:
    c) Adopted Value
    1) Ozone, heavy, moderate, or light workloads (2 hours or less)
    a) TLV:
    1) TLV-TWA: 0.2 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Not Listed
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    c) TLV Basis - Critical Effect(s): Pulm func
    d) Molecular Weight: 48
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:
    d) Adopted Value
    1) Ozone, moderate work
    a) TLV:
    1) TLV-TWA: 0.08 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Not Listed
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    c) TLV Basis - Critical Effect(s): Pulm func
    d) Molecular Weight: 48
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS10028-15-6 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Ozone
    2) REL:
    a) TWA:
    b) STEL:
    c) Ceiling: 0.1 ppm (0.2 mg/m(3))
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 5 ppm
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS10028-15-6 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Ozone, heavy work
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    2) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Ozone, light work
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    3) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Ozone, heavy, moderate, or light workloads (2 hours or less)
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    4) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Ozone, moderate work
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    5) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    6) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    7) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Ozone
    8) MAK (DFG, 2002): Category 3B ; Listed as: Ozone
    a) Category 3B : Substances for which in vitro or animal studies have yielded evidence of carcinogenic effects that is not sufficient for classification of the substance in one of the other categories. Further studies are required before a final decision can be made. A MAK value can be established provided no genotoxic effects have been detected. (Footnote: In the past, when a substance was classified as Category 3 it was given a MAK value provided that it had no detectable genotoxic effects. When all such substances have been examined for whether or not they may be classified in Category 4, this sentence may be omitted.)
    9) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS10028-15-6 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Ozone
    2) Table Z-1 for Ozone:
    a) 8-hour TWA:
    1) ppm: 0.1
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 0.2
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: (RTECS, 1996; Sax & Lewis, 1992
    1) TCLo- (INHALATION)HUMAN:
    a) 100 ppm for 1M
    b) 1 ppm
    c) 600 ppb for 2H
    d) 1860 ppb for 75M
    2) TCLo- (INHALATION)MOUSE:
    a) 5 ppm for 2H/75D
    3) TCLo- (INHALATION)RAT:
    a) 1500 ppb for 24H
    b) 1040 ppt for 24H

Pharmacology Toxicology

Toxicologic Mechanism

    A) The primary toxic effects are due to its oxidative capacity (Menzel, 1970). Ozone may react with almost any biological sustrate, but the cell membrane appears to be the site of toxicity. Reactions at the cell membrane may occur to either thiols or amino acids (Mudd & Freeman, 1977) or to unsaturated unfatty acids (Menzel, 1970).
    B) The rate of oxidation with ozone differs greatly by compounds. For example, ethylene groups are oxidized 1,000 times more quickly than other compounds (Menzel, 1984).
    C) Oxidation may result in the formation of peroxides and the production of free radicals, which result in loss of regulation of electrolytes from the cell and inhibition of metabolic chains in the mitochondria (Menzel, 1984).
    D) Respiratory effects are thought to be due to sensitization of irritant receptors, because the increases in pulmonary resistance from direct exposure to ozone persist longer than alterations in response to histamine challenge. The mechanism(s) of ozone's effects on the lungs appear to be complex and are not fully understood (Bedi et al, 1985).
    E) There are indications in man that there are secondary sites of reaction to ozone characterized by defect in the dissociation of oxygen from oxyhemoglobin (ACGIH, 1986).
    F) The ability of ozone to oxidize alpha-1-proteinase may be a factor in the development of emphysema on long term exposure to ozone.

Physicochemical

Physical Characteristics

    A) Ozone is a bluish gas with a slightly pungent odor, which may be detected at the 0.05-0.3 ppm level (Beard, 1982).
    B) bluish gas or blue liquid (Budavari, 1989)
    C) colorless to bluish gas, dark blue liquid, or blue-black crystals (EPA, 1985)
    D) between -111.9 degrees C (-169.6 degrees F) and -192.7 degrees C (-314 degrees F), ozone is a dark blue liquid (EPA, 1985)
    E) below -192.7 degrees C (-314 degrees F), ozone exists as blue-black crystals (EPA, 1985)
    F) pleasant, characteristic odor in concentrations of less than 2 ppm (Budavari, 1989)
    G) Concentrations of 1 ppm produce a disagreeable sulfur-like odor (Lewis, 1992).

Molecular Weight

    A) 48.00

References

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