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OZONE

See Occupational Exposure Standards

Human Health Effects:

Evidence for Carcinogenicity:

A4; Not classifiable as a human carcinogen. /Heavy work, moderate work, light work, or heavy, moderate, or light workloads (</=2 hours)/
[American Conference of Governmental Industrial Hygienists. TLVs & BEIs: Threshold limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2002. Cincinnati, OH. 2002.46]**QC REVIEWED**

Human Toxicity Excerpts:

THE PRIMARY SITE OF ACUTE INJURY IS THE LUNG WHICH IS CHARACTERIZED BY PULMONARY CONGESTION, EDEMA, AND HEMORRHAGE. THERE ARE INDICATIONS IN MAN THAT THERE ARE SECONDARY SITES OF REACTION ... CHARACTERIZED BY A DEFECT IN OXYGEN DISSOCIATION FROM OXYHEMOGLOBIN.
[American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986.453]**PEER REVIEWED**

LIQUID ... ON CONTACT WITH SKIN OR MUCOUS MEMBRANES MAY PRODUCE SEVERE BURNS.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Volumes I and II. New York: McGraw-Hill Book Co., 1971. 1580]**PEER REVIEWED**

WHEN INHALED AT CONCN NOT ACUTELY INJURIOUS PER SE MAY INITIATE, ACCELERATE OR EXACERBATE RESPIRATORY TRACT DISEASE OF BACTERIAL OR VIRAL ORIGIN. HUMAN VOLUNTEERS EXPOSED AT 0.5 PPM THREE HR A DAY, SIX DAYS A WK, FOR 12 WK, SHOWED SIGNIFICANT CHANGES IN LUNG FUNCTION.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values, 4th ed., 1980. Cincinnati, Ohio: American Conference of Governmmental Industrial Hygienists, Inc., 1980.316]**PEER REVIEWED**

... LOWERING OF BLOOD PRESSURE, OWING TO CENTRALLY CONDITIONED DILATION OF THE PERIPHERAL BLOOD VESSELS.
[Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963. 917]**PEER REVIEWED**

... 0.35 PPM FOR 2 HR INCR RESP RATE & DECR TIDAL VOL ... 2 PPM ... INHALED FOR 2 HR, CAUSES SENSE OF PRESSURE IN CHEST, TEMPORARY EXHILARATION FOLLOWED BY DEPRESSION & DECR IN LUNG CAPACITY. ... (5 TO 10 PPM) CAUSE INCR IN PULSE ... RESP EFFORT ... & WHEN INHALED FOR MORE THAN AN HR MAY CAUSE PULMONARY EDEMA & DEATH.
[Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972. 191]**PEER REVIEWED**

... DISCOMFORT TO EXPOSED INDIVIDUALS IN FORM OF ... DRYNESS OF THROAT & MUCOUS MEMBRANES OF NOSE & EYES FOLLOWING EXPOSURES OF SHORT DURATION.
[American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986.453]**PEER REVIEWED**

... EXPOSED 30 MEN TO 0.4 PPM OF OZONE FOR 4 HR & STUDIED LYMPHOCYTE CULTURES TAKEN BEFORE & AT INTERVALS OF ZERO, 3 DAYS, 2 WK, & 4 WK AFTER EXPOSURE. THEY FOUND NO TREND TOWARD SIGNIFICANT CHANGES IN CHROMOSOMES.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 4085]**PEER REVIEWED**

SIX GROUPS OF HEALTHY YOUNG MALE VOLUNTEERS WERE EXPOSED FOR 2.5 HR TO ONE OF THE FOLLOWING OZONE CONCN: 0.0, 0.12, 0.18, 0.24, 0.30, OR 0.40 PPM. FIFTEEN MINUTE PERIODS OF REST & EXERCISE (65 L/MIN VENTILATION) WERE ALTERNATED DURING THE FIRST 2 HR OF EXPOSURE. COUGHING WAS OBSERVED AT ALL LEVELS OF OZONE EXPOSURE. SMALL CHANGES IN FORCED-EXPIRATORY SPIROMETRIC VARIABLES (FORCED VITAL CAPACITY (FVC), FORCED EXPIRATORY VOLUME IN 1 S, & MEAN EXPIRATORY FLOW RATE BETWEEN 25 & 75% FVC) WERE OBSERVED AT 0.12 & 0.18 PPM OZONE, & LARGER CHANGES WERE FOUND AT OZONE LEVELS GREATER THAN OR EQUAL TO 0.24 PPM. CHANGES IN TIDAL VOLUME & RESPIRATORY FREQUENCY DURING EXERCISE, SPECIFIC AIRWAY RESISTANCE, THE PRESENCE OF PAIN ON DEEP INSPIRATION, & SHORTNESS OF BREATH OCCURRED AT OZONE LEVELS GREATER THAN OR EQUAL TO 0.24 PPM. STIMULATION OF AIRWAY RECEPTORS IS PROBABLY THE MECHANISM RESPONSIBLE FOR THE MAJORITY OF OBSERVED CHANGES; HOWEVER, THE EXISTENCE OF A SECOND MECHANISM OF ACTION IS POSTULATED.
[MCDONNELL WF ET AL; J APPL PHYSIOL 54 (5): 1345 (1983)]**PEER REVIEWED**

Fifteen trained competitive cyclists (14 males, 1 female) participated in a randomized crossover study consisting of double-blinded inhalations of albuterol (180 ug) and placebo approximately 30 min prior to heavy continuous exercise for 60 min followed by a maximal sprint until exhaustion. Albuterol pretreatment resulted in modest but significant bronchodilation as compared to placebo; however, it did not prevent ozone induced respiratory symptoms, decrements in forced vital capacity, forced expired volume in one second, maximum midexpiratory flow rate, and positive histamine challenges as compared to that with placebo/ozone. The peak expiratory volume was significantly lower with ozone than with filtered air.
[Gong H et al; Arch Environ Health 43 (1): 46-53 (1988)]**PEER REVIEWED**

Nine asthmatic and nine normal subjects (18 to 35 yr old nonsmokers) underwent two randomly assigned 2 hr exposures to filtered, purified air and 0.4 ppm ozone with alternating 15 min periods of rest and exercise on a cycle ergometer. Before and after each exposure, pulmonary function and bronchial responsiveness to methacholine were measured and symptoms recorded. Ozone exposure was associated with a statistically significant decr in forced vital capacity, forced expired volume in 1 sec, and forced expired flow at 25-75% in both normal and asthmatic subjects. Comparing the response of asthmatic and normal subjects to ozone revealed a significantly greater decr in forced expired volume in 1 sec and forced expired flow at 25-75% in the asthmatic subjects.
[Kreit JW et al; J Appl Physiol 66 (1): 217-22 (1989)]**PEER REVIEWED**

A cross sectional epidemiological study investigating the respiratory health of children in two Canadian communities was conducted in 1983-1984 in Tillsonburg, Ontario, located in a region of moderately elevated concentrations of transported air pollutants and in Portage la Prairie, Manitoba, situated in a low pollution area. Seven hundred and thirty five children aged 7 to 12 were studied in the first town and 895 in the second. Respiratory health was assessed by measurement of the forced vital capacity and forced expiratory volume in 1 sec and by a parent questionnaire concerning respiratory symptoms and illness. Sulfur dioxide, sulfate, and particulate nitrate levels were significantly higher in Tillsonburg than in Portage la Prairie, but nitrogen dioxide and inhalable particles differed little between the communities. Ozone levels were highest during the summer and lowest during the winter; maximum 1 hr values in Ontario rarely exceeded 40 in October through March and commonly exceeded the 80 ppb limit during the summer. In Manitoba monthly mean ozone concn were lower and less variable (10 to 30 ppb) than in Ontario. Tillsonburg children had statistically significant lower levels of 2% for forced vital capacity and 1.7% for forced expiratory volume in 1 sec as compared with children in Portage la Prairie. The prevalence of chronic respiratory symptoms and illnesses was similar in the two communities.
[Stern B et al; Environ Res 49 (1): 20-39 (1989)]**PEER REVIEWED**

Human blood mononuclear cells were exposed to ozone in vitro and then analyzed for competence in mitogen-induced proliferation and for interleukin 1 and interleukin 2 production. Proliferative responses induced by phytohemagglutinin,concanavalin A, and pokeweed mitogen were all depressed in lymphocytes exposed to an ozone concentration of 1 ppm for 4 to 6 hours. Responses to the ozone effect were as follows: pokeweed mitogen, 38% suppression; Concanavalin A, 23% suppression; and phytohemagglutinin, 18% suppression. Pokeweed responses were affected at an ozone concentration as low as 0.1 ppm; however, no suppression of Concanavalin A induced proliferation was seen below 0.18 ppm or of phytohemagglutinin induced proliferation below 0.5 ppm. When lymphocytes and monocytes were exposed separately to ozone and then mixed back with control cells, both cell types were affected by the ozone exposure. The functional defects were additive. Interleukin 1 production induced by endotoxin was not affected by ozone exposure, while surface expression of HLA-DR on exposed monocytes was reduced by 40% 24 hours after exposure. Lymphocytes exposed to ozone produced 46% less interleukin 2 while expressing a similar surface density of interleukin 2 receptors.
[Becker S et al; J Toxicol Environ Health 26 (4): 469-83 (1989)]**PEER REVIEWED**

Pulmonary function hyperresponsiveness, defined as enhanced response on re-exposure to ozone (O3) compared with initial O3 exposure, was examined at two levels of O3 exposure. Fifteen aerobically trained males (ages 19 to 34) completed seven 1 hr exposures of continuous exercise (bicycle ergometer) at work rates eliciting a mean minute ventilation of 60 l/min. Three sets of consecutive day exposures, involving day l/day 2 exposures to 0.20/0.20 ppm O3, 0.35/0.20 ppm O3, and 0.35/0.35 ppm O3, were randomly delivered via an obligatory mouthpiece inhalation system. A filtered air exposure was randomly placed 24 hr before one of the 3 sets. Treatment effects were assessed by standard pulmonary function tests, exercise ventilatory pattern (ie, respiratory frequency and tidal volume) changes and subjective symptom response. Percent change values for each protocol (post-pre)/(pre) x 100 were used for statistical comparison to obtain specific significant mean differences. Initial exposures to 0.35 and 0.20 ppm O3 had a statistically significant effect, compared with filtered air, on all measurements. On re-exposure to 0.35 ppm 03 24 hr after initial 0.35 ppm O3 exposure, significant hyperresponsiveness was demonstrated for forced vital capacity, forced expiratory volume in 1 sec, respiratory frequency, tidal volume, and total subjective symptom score. Exposure to 0.20 ppm O3 24 hr after 0.35 ppm O3 exposure, however, resulted in significantly enhanced responses (compared with initial 0.20 ppm O3 exposure) only for forced expiratory volume, respiratory frequency, and tidal volume. Re-exposure to 0.20 ppm O3, 24 hr after initial exposure to 0.20 ppm O3, did not result in significantly enhanced respiratory frequency, tidal volume, or subjective symptom responses, but a trend toward an enhanced forced expiratory volume was observed.
[Brookes KA et al; J Appl Physiol 66 (6): 2756-62 (1989)]**PEER REVIEWED**

Twenty ozone (O3)-sensitive and 20 O3-nonsensitive subjects were selected from a pool of 75 normal healthy college aged males who had been previously exposed to 0.35 ppm O3 for 1 hr at an exercising expiratory vol of 60 l/min. The selection criterion used was the observed decrement in forced expiratory vol(1) after the O3 exposure: O3 sensitive, forced expiratory vol(1) decrement > 24%; O3 nonsensitive, forced expiratory vol(1) decrement < 11%. Each subject was exposed to filtered air and to 0.20 and 0.35 ppm O3 for 80 min while exercising at an expiratory vol of 50 l/min. These exptl protocols were divided into two 40-min sessions separated by a period of 4 to 10 min. Prostaglandin F sub 2 alpha, forced vital capacity, forced expiratory vol(1), and forced expiratory flow rate in the middle half of forced vital capacity (FEF sub 25-75 were) evaluated before, during, and after each protocol. Analysis of forced vital capacity and forced expiratory vol(1) data revealed significant group, O3 concn, and time effects. The 2 O3-sensitive groups were significantly different in the 0.20 ppm postexposure protocol, and in both 0.35 ppm midexposure and postexposure protocols. The nonsensitive group revealed no significant O3 concn or time effects for either forced vital capacity or forced expiratory vol(1) responses, while these responses were significantly reduced postexposure in the O3 sensitive group at both O3 levels. Specific airway conductance (S sub Gaw) and thoracic gas vol (V sub tg) were measured before and after each protocol. Analysis of thoracic gas vol revealed no significant effect for either group or O3 concn. There was, however, a significant effect on specific airway conductance responses in the O3 sensitive group at both O3 levels when compared with the filtered air protocol. Analysis revealed significant group, O3 concn, and time effects for V sub T and respiratory frequency responses. There were also significant effects between group, O3 concn, and times for overall rating of subjective symptoms. Plasma prostaglandin F sub 2 alpha was significantly increased in the O3-sensitive group during and after the 0.35 ppm O3 exposure.
[Schelegle ES et al; Am Rev Respir Dis 140 (1): 211-6 (1989)]**PEER REVIEWED**

... Ozone is not effectively scrubbed /by the mucus layer in the upper portion of the respiratory tract/ ... and may cause significant toxic injury to the pulmonary region.
[Cralley, L.J., L.V. Cralley (eds.). Patty's Industrial Hygiene and Toxicology. Volume III: Theory and Rationale of Industrial Hygiene Practice. 2nd ed., 3A: The Work Environment. New York, NY: John Wiley Sons, 1985.152]**PEER REVIEWED**

Respiratory effects - Acute lung damage/edema.
[Cralley, L.J., L.V. Cralley (eds.). Patty's Industrial Hygiene and Toxicology. Volume III: Theory and Rationale of Industrial Hygiene Practice. 2nd ed., 3A: The Work Environment. New York, NY: John Wiley Sons, 1985.177]**PEER REVIEWED**

Airline flight attendants on trans-Pacific flights reported an incr incidence of respiratory symptoms, attributed to high-altitude ozone exposure.
[Zenz, C. Occupational Medicine-Principles and Practical Applications. 2nd ed. St. Louis, MO: Mosby-Yearbook, Inc, 1988. 753]**PEER REVIEWED**

Ozone ... produces mucosal damage via direct biochemical effects.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 885]**PEER REVIEWED**

Mild to moderate exposure produces upper respiratory tract symptoms and eye irritation (eg lacrimation, burning of the eyes and throat, nonproductive cough, headache, substernal soreness, bronchial irritation, acrid taste and smell). More severe exposures, such as that seen in an industrial setting, may produce significant respiratory distress with dyspnea, cyanosis, and pulmonary edema. Chest x-rays show increased bronchovascular markings and bilateral lung densities. Symptoms resolve over 1 to 2 weeks although fatigue, headache, and exertional dyspnea may persist for several months. ... Ozone may exacerbate the small airway impairment of smoking adults.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 885]**PEER REVIEWED**

Exposure to ozone,a toxic component of photochemical smog, results in significant airway inflammation, respiratory discomfort, and pulmonary function impairment. These effects can be reduced via pretreatment with anti-inflammatory agents. Progesterone, a gonadal steroid, is known to reduce general inflammation in the uterine endometrium. However, it is not known whether fluctuations in blood levels of progesterone, which are experienced during the normal female menstrual cycle, could alter ozone inflammatory induced pulmonary responses. In this study, the hypothesis that young, adult females are more responsive to ozone inhalation with respect to pulmonary function impairment during their follicular menstrual phase when progesterone levels are lowest than during their mid-luteal phase when progesterone levels are highest, was tested. Nine subjects with normal ovarian function were exposed in random order for 1 hr each to filtered air and to 0.30 ppm ozone in their follicular and mid-luteal menstrual phases. Ozone responsiveness was measured by percent change in pulmonary function from pre- to postexposure. Significant gas concn effects (filtered air versus ozone) were observed for forced vital capacity, forced expiratory volume in 1 sec, and forced expiratory flow between 25 and 75% of forced vital capacity (p < 0.05). More importantly, the pulmonary function flow rates, forced expiratory volume in 1 sec, and forced expiratory flow between 25 and 75% of forced vital capacity (p < 0.05), showed a significant menstrual phase and gas concn interaction effect, with larger decrements observed in the follicular menstrual phase when progesterone concn were significantly lower. It was concluded that young, adult females appear to be more responsive to acute ozone exposure during the follicular phase than during the mid-luteal phase of their menstrual cycles.
[Fox SD et al; Environ Health Perspect 101 (3): 242-4 (1993)]**PEER REVIEWED**

Acute exposure of humans to ozone is known to acutely cause pulmonary function decrements, inflammation, and increased permeability of pulmonary epithelium. A single study in humans has also shown that mucociliary transport increases during acute ozone exposure. Because different responses have shown a different time course of recovery after exposure, it was important to examine mucociliary transport at a different time after the cessation of ozone exposure. Fifteen healthy male and female nonsmoking subjects were exposed, on different occasions, to clean air and 0.4 ppm ozone for 1 hr while they exercised continuously. Pulmonary function was measured immediately before and after exposure and 90 min and 24 hr after exposure. Between 2 and 5 hr after each exposure, retention of inhaled 5-microns mass median aerodynamic diameter (99)mTc-labeled Fe2O3 particles was measured. Each subject returned the next day for a final particle retention measurement. Despite significant changes in pulmonary function, there was no difference in mean whole lung retention time of particles between clean air (77.9 + or - 0.8 (standard error) min) and ozone (78.0 + or - 0.8 min) exposures, indicating that mucociliary transport is unaffected by ozone exposure when it is measured 2 hr after exposure.
[Gerrity TR et al; J Appl Physiol 74 (6): 2984-9 (1993)]**PEER REVIEWED**

An investigation was made concerning complaints of poor indoor air quality. Complaints included breathing problems, itching, headaches, coughing, congestion, fiberglass from ceiling panels, and paper dust. The site was formerly a warehouse which was converted to office space. Five general area, full shift air samples were collected for total dust concn. The eight hour time weighted average results ranged from not detectable to 0.21 mg/cu m. Ozone concn were equal to or greater than the NIOSH Recommended Exposure Limit of 0.1 ppm at microfiche reader printer exhaust ports. Carbon dioxide levels in the building ranged from 425 ppm to 875 ppm. Temperature ranged from 72.0 to 80.0 deg F. Relative humidity indoors ranged from 48.4 to 64.4%. The most common symptoms reported by the workers were mucous membrane irritation, fatigue or sleepiness, and headache. It was concluded that clear evidence was not found to explain all of the symptoms reported. Respiratory symptoms may be explained by ozone levels near the microfilm reader printers. Psychosocial conditions may have been contributory.
[Echt A et al; Govt Reports Announcements & Index (GRA&I), Issue 20 (1993)]**PEER REVIEWED**

An investigation was made of indoor air quality in the church office. Particular attention was directed toward laser printer and photocopier emissions. Employees had complained of headaches, dizziness, confusion, nausea, eye irritation, and dry nose and throat. Day shift employees performed general office duties, often using a photocopier and a laser printer. Real time ozone concn ranged from below the limit of detection to 0.05 ppm in the breathing zone, all below the NIOSH limit for short term exposure of 0.10 ppm. Ozone concn as high as 0.56 ppm were detected at the laser printer exhaust. Carbon dioxide concn ranged from 400 to 850 ppm. Respirable dust concn ranged from below the limit of detection to 90 ug/cu m. Carbon monoxide levels were not above the limit of detection of 5 ppm. No volatile organic carbons were detected. Temperature and relative humidity levels were within the guidelines. Some of the symptoms were consistent with ozone exposure. It was concluded that efforts should be made to reduce ozone exposures. Relocating the laser printer, providing additional outside air to the building, and checking for possible overloading or inefficiency in the ozone filter in the printer is recommended.
[Cook CK; Govt Reports Announcements & Index (GRA&I), Issue 14 (1992)]**PEER REVIEWED**

An investigation was made of indoor air quality in the church office. Particular attention was directed toward laser printer and photocopier emissions. Employees had complained of headaches, dizziness, confusion, nausea, eye irritation, and dry nose and throat. Day shift employees performed general office duties, often using a photocopier and a laser printer. Real time ozone concn ranged from below the limit of detection to 0.05 ppm in the breathing zone, all below the NIOSH limit for short term exposure of 0.10 ppm. Ozone concn as high as 0.56 ppm were detected at the laser printer exhaust. Carbon dioxide concn ranged from 400 to 850 ppm. Respirable dust concn ranged from below the limit of detection to 90 ug/cu m. Carbon monoxide levels were not above the limit of detection of 5 ppm. No volatile organic carbons were detected. Temperature and relative humidity levels were within the guidelines. Some of the symptoms were consistent with ozone exposure. It was concluded that efforts should be made to reduce ozone exposures. Relocating the laser printer, providing additional outside air to the building, and checking for possible overloading or inefficiency in the ozone filter in the printer is recommended.
[Cook CK; Hazard Evaluations and Technical Assistance Branch, NIOSH, U.S. Department of Health and Human Services, Cincinnati, Ohio, Report No. HETA-91-158-2161, 17 p (1991)]**PEER REVIEWED**

Evidence that ozone is radiomimetic and may be the cause of an excess of leukaemia found in certain occupational groups (electricians, electronic technicians, linemen, television and radio repairmen, and motion picture projectionists) is presented. These workers are all exposed to electrical or magnetic fields but they are also exposed to ozone originating from electrical discharges which occur in these working environments.
[Hogendoorn M; Chemistry in Britain 19 (11): 908 (1983)]**PEER REVIEWED**

REPEATED EXPOSURES (3 TIMES) TO LOW CONCENTRATIONS OF OZONE (0.20 PPM) IN 21 HUMAN VOLUNTEERS DID NOT DEMONSTRATE PULMONARY FUNCTION ADAPTATION OR DESENSITIZATION ON SUBSEQUENT EXPOSURE TO HIGHER OZONE CONCENTRATIONS (0.42 OR 0.50 PPM).
[GLINER JA ET AL; AM REV RESPIR DIS 127 (1): 51 (1983)]**PEER REVIEWED**

Skin, Eye and Respiratory Irritations:

Irritation - eye, nose, throat, skin - Marked.
[Cralley, L.J., L.V. Cralley (eds.). Patty's Industrial Hygiene and Toxicology. Volume III: Theory and Rationale of Industrial Hygiene Practice. 2nd ed., 3A: The Work Environment. New York, NY: John Wiley Sons, 1985.177]**PEER REVIEWED**

Gas irritates the upper respiratory system strongly.
[Armour, M.A. Hazardous Laboratory Chemicals Disposal Guide. Boca Raton, FL: CRC Press Inc., 1991. 269]**PEER REVIEWED**

Populations at Special Risk:

Preclude from exposure those personnel with pulmonary diseases.
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 393]**PEER REVIEWED**

Probable Routes of Human Exposure:

... FOUND ... AROUND SOURCES OF X-RAYS AND UV RAYS, ELECTRIC ARCS (WELDING AND SPECTROGRAPHIC EQUIPMENT, FOR EXAMPLE), MERCURY VAPOR LAMPS, ULTRA-BILLION-VOLT LINEAR ACCELERATORS AND ELECTRICAL DISCHARGES IN GENERAL.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 1579]**PEER REVIEWED**

Emergency Medical Treatment:

Emergency Medical Treatment:

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The following Overview, *** OZONE ***, is relevant for this HSDB record chemical.

Life Support:
   o   This overview assumes that basic life support measures
       have been instituted.
Clinical Effects:
  0.2.1 SUMMARY OF EXPOSURE
   0.2.1.1 ACUTE 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.
  0.2.3 VITAL SIGNS
   0.2.3.1 ACUTE EXPOSURE
     A)  Decreased pulse rate and blood pressure may occur in
         humans after inhalation.
  0.2.4 HEENT
   0.2.4.1 ACUTE EXPOSURE
     A)  Conjunctivitis has been reported. Levels of 2 ppm for 2
         hours produced throat and mouth dryness.
  0.2.5 CARDIOVASCULAR
   0.2.5.1 ACUTE EXPOSURE
     A)  Cardiovascular effects reported have been secondary to
         respiratory changes.
  0.2.6 RESPIRATORY
   0.2.6.1 ACUTE EXPOSURE
     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
   0.2.7.1 ACUTE EXPOSURE
     A)  Drowsiness, dizziness, headache and fatigue have been
         reported after industrial exposure.
  0.2.8 GASTROINTESTINAL
   0.2.8.1 ACUTE EXPOSURE
     A)  Anorexia, nausea and vomiting have been seen.
  0.2.9 HEPATIC
   0.2.9.1 ACUTE EXPOSURE
     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
   0.2.13.1 ACUTE EXPOSURE
     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
   0.2.14.1 ACUTE EXPOSURE
     A)  Severe burns can occur from direct contact with the
         cryogenic liquid or with escaping compressed gas.
  0.2.17 METABOLISM
   0.2.17.1 ACUTE EXPOSURE
     A)  Enzymatic alterations were observed.
   0.2.17.2 CHRONIC EXPOSURE
     A)  The ability of ozone to oxidize alpha-1-proteinase may
         be a factor in the development of emphysema on long
         term exposure to ozone.
  0.2.19 IMMUNOLOGIC
   0.2.19.2 CHRONIC EXPOSURE
     A)  Immunosuppression has been reported in guinea pigs and
         mice with chronic low exposures. This effect has not
         been noted in humans.
  0.2.20 REPRODUCTIVE HAZARDS
    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
   0.2.21.1 IARC CATEGORY
     A)  IARC Carcinogenicity Ratings for CAS10028-15-6 (IARC,
         2004):
      1)  Not Listed
   0.2.21.2 HUMAN OVERVIEW
     A)  At the time of this review, no studies were found on
         the potential carcinogenicity of ozone in humans.
   0.2.21.3 ANIMAL OVERVIEW
     A)  In mice, ozone was found to be an equivocal tumorigenic
         agent and neoplastic by RTECS criteria with the
         presence of tumors. Oncogenic transformation was
         observed in mice fibroblasts. Ozone produced pulmonary
         tumors in mice.
  0.2.22 GENOTOXICITY
    A)  Ozone is radiomimetic; mutations and chromosome
        aberrations have been produced at high concentrations.
  0.2.23 OTHER
   0.2.23.1 ACUTE EXPOSURE
     A)  There is some evidence that humans may develop a
         tolerance to the effects of low concentrations.
Laboratory:
   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 inhaled
        beta2 agonist and oral or parenteral corticosteroids.
    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 gas 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: Irrigate exposed eyes with copious
        amounts of room temperature water for at least 15
        minutes. If irritation, pain, swelling, lacrimation, or
        photophobia persist, the patient should be seen in a
        health care 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.
PRODUCTS OF COMBUSTION)

[Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2004; CCIS Volume 122, edition expires Nov, 2004. Hall AH & Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2004; CCIS Volume 122, edition expires Nov, 2004.]**PEER REVIEWED**

Antidote and Emergency Treatment:

Treatment is supportive, similar to that for smoke inhalation and chlorine
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 885]**PEER REVIEWED**

Animal Toxicity Studies:

Evidence for Carcinogenicity:

A4; Not classifiable as a human carcinogen. /Heavy work, moderate work, light work, or heavy, moderate, or light workloads (</=2 hours)/
[American Conference of Governmental Industrial Hygienists. TLVs & BEIs: Threshold limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2002. Cincinnati, OH. 2002.46]**QC REVIEWED**

Non-Human Toxicity Excerpts:

EXPOSURES AT 0.1 PPM AND 0.2 PPM SEVEN HOURS A DAY FOR THREE WK RESULTED IN ... INCR NEONATAL MORTALITY IN MICE.
[American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986.453]**PEER REVIEWED**

... ANIMALS WERE EXPOSED REPEATEDLY TO THE INHALATION OF 1 PPM OZONE OVER A PROLONGED PERIOD. THE TERMINAL AIRWAYS OF THE LUNGS WERE THICKENED, THE AIR PASSAGES NARROWED, WITH FIBROTIC TISSUE FORMATION, RESULTING IN DIMINISHED CAPACITY TO MOVE AIR THROUGH THE LUNGS.
[Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963. 917]**PEER REVIEWED**

ANIMALS ... EXPOSED ARE AT FIRST HYPERACTIVE, BUT SOON BECOME QUIET, AS THOUGH DEPRESSED. ACUTE EXPOSURE OF RABBITS ... INCR NUMBER OF HETEROPHILIC LEUKOCYTES, BUT DECR ALVEOLAR MACROPHAGES & AMT OF PHAGOCYTOSIS OF INSTILLED STREPTOCOCCI.
[Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972. 191]**PEER REVIEWED**

IN CHINESE HAMSTERS THAT INHALEDOZONE, NO INCR IN CHROMOSOME-TYPE ABERRATION LEVELS WAS OBSERVED, THOUGH SMALL INCR IN CHROMATID ABERRATION LEVELS WAS SEEN.
[TICE RR ET AL; MUTAT RES 58 (2-3): 293 (1978)]**PEER REVIEWED**

... EXPOSED PREGNANT RATS TO SEVERAL CONCN OF OZONE FOR SEVERAL DAYS AT DIFFERENT STAGES OF GESTATION. EXPOSURES OF 0.44 PPM 8 HR/DAY THROUGHOUT THE PERIOD OF ORGANOGENESIS PRODUCED NO SIGNIFICANT EFFECTS. HIGHER CONCN, UP TO 1.97 PPM, APPEARED TO CAUSE MINIMAL TERATOGENESIS. IN MIDGESTATION, ADMIN 0F 1.26 PPM WAS FOLLOWED BY INCREASED RATES OF FETAL ABSORPTION.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 4075]**PEER REVIEWED**

AIRWAY RESPONSIVENESS & INFLAMMATION WERE ASSESSED IN ANESTHETIZED DOGS BEFORE OZONE EXPOSURE & THEN 1HR & 1 WEEK AFTER OZONE (2.1 PPM, 2 HR). AIRWAY RESPONSIVENESS (INCREASES IN PULMONARY RESISTANCE) INCREASED MARKEDLY 1 HR AFTER OZONE EXPOSURE & RETURNED TO CONTROL LEVELS 1 WK LATER IN EACH OF 6 DOGS, BUT DID NOT CHANGE AFTER OZONE IN ANOTHER 4 DOGS. DOGS THAT BECAME HYPERRESPONSIVE DEVELOPED MARKED & REVERSIBLE INCREASES IN THE NUMBER OF EPITHELIAL NEUTROPHILS. IN DOGS, OZONE-INDUCED AIRWAY HYPERRESPONSIVENESS MAY DEPEND ON THE DEVELOPMENT OF AN ACUTE INFLAMMATORY RESPONSE IN THE AIRWAYS.
[HOLTZMAN MJ ET AL; AM REV RESPIR DIS 127 (6): 686 (1983)]**PEER REVIEWED**

OZONE-INDUCED LUNG INJURY IN MALE RATS WAS ASSESSED BY ANALYSIS OF PULMONARY FUNCTION, STRUCTURE, & TISSUE COMPOSITION AFTER 62 EXPOSURES TO 0-2.0 PPM (6 HR/DAY, 5 DAYS/WK). FROM LOW TO HIGH DOSE, PULMONARY RESISTANCE RANGED FROM 155-257% OF THE CONTROL MEAN. SIMILARLY, EXPIRATORY FLOW RATES AT 25% OF FORCED VITAL CAPACITY DECREASED BY 34-79%. SEVERE PULMONARY DYSFUNCTION & ALTERED DISTRIBUTION OF VENTILATION WAS NOTED IN THE 2.0 PPM EXPOSURE GROUP. REDUCTION IN PULMONARY ELASTIN & HYDROXYPROLINE, & THE DEPRESSED EFFORT-INDEPENDENT AIRFLOW OF THE 0.2 & 0.8 PPM RATS, WITHOUT APPARENT CHANGE IN UPSTREAM AIRWAY RESISTANCE, SUGGEST THE PULMONARY LESION INVOLVED REDUCED PARENCHYMAL ELASTICITY RATHER THAN DIRECT SMALL-AIRWAY OBSTRUCTION.
[COSTA DL ET AL; ADV MOD ENVIRON TOXICOL 5 (INT SYMP BIOMED EFFECTS OZONE RELAT PHOTOCHEM OXID): 369 (1983)]**PEER REVIEWED**

BONNET MONKEYS (MACACA RADIATA) WERE EXPOSED TO 0.0, 0.5, OR 0.8 PPM OZONE FOR 7, 28, OR 90 CONSECUTIVE DAYS, 8 HR/DAY. MORPHOLOGIC CHANGES WERE PRINCIPALLY CHARACTERIZED AS LOW-GRADE CHRONIC RESPIRATORY BRONCHIOLITIS. MAJOR FEATURES NOTED WERE INTRALUMINAL ACCUMULATIONS OF MACROPHAGES & HYPERTROPHY & HYPERPLASIA OF CUBOIDAL BRONCHIOLAR EPITHELIAL CELLS. THE MAGNITUDE OF INFLAMMATION WAS GREATEST AT THE 0.8 PPM OZONE EXPOSURE LEVEL. DIFFERENTIAL CELL COUNTS DEMONSTRATED AN INCREASE IN THE PROPORTION OF CUBOIDAL BRONCHIOLAR CELLS CONSTITUTING THE RESPIRATORY BRONCHIOLAR EPITHELIUM. EPITHELIAL HYPERPLASIA (INCREASED NUMBER OF CELLS PER MILLIMETER OF AIRWAY LENGTH) PERSISTED THROUGH 90 DAYS OF EXPOSURE AT A LEVEL SLIGHTLY ABOVE THAT PRESENT AT 7 DAYS.
[EUSTIS SL ET AL; AM J PATHOL 105 (2): 121 (1981)]**PEER REVIEWED**

In an experimental animal study the concn-response effects of inhaled ozone and phosgene in different species of laboratory animals were compared. The effect of 4 hr exposures to ozone at concn of 0.2, 0.5, 1.0, and 2.0 ppm, and to phosgene at 0.1, 0.2, 0.5, and 1.0 ppm was determined in rabbits, guinea pigs, rats, hamsters ,and mice. Lavage fluid protein accumulation 18-20 hr after exposure was used as the indicator of ozone and phosgene induced pulmonary edema. All species had similar basal levels of lavage fluid protein (250-350 mg/ml). All of the experiments showed a trend of increasing lavage fluid protein with increasing ozone concentration. Ozone effects were most marked in guinea pig, which showed a significantly elevated level of protein (p< 0.05) at 0.2 ppm and above. Mice, hamsters, and rats showed significant effects at 1.0 ppm ozone and above (p< 0.05), while rabbits responded only at 2.0 ppm ozone (p< 0.05). Phosgene similarly affected mice, hamters, and rats at 0.2 ppm and above (p< 0.05), while guinea pigs and rabbits responded significantly (p< 0.05) at 0.5 ppm and above. Lavage fluid recovery was lower following exposure to higher levels of ozone but not phosgene.
[Hatch G E et al; J Toxicol Environ Health 19: 43-53 (1986)]**PEER REVIEWED**

Seedlings of Jeffrey pine (Pinus jeffreyi) and giant sequoia (Sequoiadendron gigantea) were more susceptible to leaf chemical changes following exposure in greenhouses to acid mist (pH 3.4 to 2.0) or acid mist/ozone combinations, than to ozone alone (0.1 to 0.2 ul/l), when plants were exposed to alternating doses of these pollutants. Experimental studies were conducted for 6 weeks starting 23 May 1985 and for 9 weeks starting 2 May 1986. Ozone treatment produced no effects in either species except for a rise in potassium and magnessium in new leaves of Jeffrey pine in the 1986 experiment. In field studies, limited foliage samples collected from these two species in 1985 and 1986 in Sequoia/Kings Canyon National Parks did not indicate any clearcut or severe effects of ozone alone on leaf chemistry.
[Westman WE, Temple PJ; Environ Pollut 57 (1): 9-26 (1989)]**PEER REVIEWED**

Three groups of 7 male albino rabbits each were exposed respectively to filtered air alone (control group), filtered air with 2 ppm ozone (O3) for 6 hr daily for 3 days, or filtered air with 1 ppm O3 for 6 hr daily for 7 days in stainless steel inhalation chambers kept at 23 deg C. About 17 hr after exposure, rabbits were subjected to several respiratory tests. After the respiratory tests, the rabbits were sacrificed and lungs were examined histologically. The lung of each rabbit exposed to 2 ppm O3 for 6 hr daily for 3 days showed the earlier stage of edema, and tended to trap air as distending pressure was lowered at the measurement of volume-pressure relationship. In this group of animals, dynamic compliance decr, pulmonary flow resistance incr and the flow-volume curve obtained by forced deflation showed a definitely altered slope with reduced flows at the latter part of a descending limb. In rabbits exposed to 1 ppm O3 for 6 hr daily for 6 days, an incr in pulmonary flow resistance was observed to the extent of that found in the other O3 exposed group. Light microscopic study of the airways of O3 exposed rabbits revealed varying degrees of epithelial damages and submucosal edema in the large airways and in terminal and respiratory bronchioles, and thickening of alveolar walls in the proximal alveolar ducts.
[Yokoyama et al; Environ Pathol Toxicol Oncol 9 (1): 95-108 (1989)]**PEER REVIEWED**

A mixture of ladino clover (Trifolium repens) and tall fescue (Festuca arundinacea) was exposed to chronic doses of ozone (O3) at two soil-moisture levels over two growing seasons. The mixture was seeded on 15 Sept 1983 and exposed to six levels of O3 in 3 m diameter open-top chambers for 12 hr/day from 26 Apr to 18 Oct in 1984, and from 13 Apr to 22 Oct in 1985. The chamber O3 treatments were charcoal-filtered air, nonfiltered air, and four NF treatments to which different levels of O3 were added. The six seasonal 12 hr/day mean O3 concn ranged from 0.025 to 0.092 ul/l. Soil-moisture treatments, obtained by differential irrigation, were well-watered (irrigated when soil matric potential in one or more plots reached -0.4 MPa) or water-stressed (watered at -1.2 MPa). A soil-moisture deficit occurred intermittently in water stressed plants during both seasons. Shoots were harvested when plants reached a height of 20-25 cm. Total forage (clover and fescue) yield in the water stressed plots (O3 levels combined) was 12% less than that in the well-watered plots in 1984 and 14% less in 1985. Clover was much more sensitive than fescue to O3. Ozone-induced suppression of clover growth was accompanied by an increase in fescue growth, and the effects increased as O3 increased. Over the two seasons, est effects of ambient levels of O3 (2 yr seasonal 12 hr/day mean of 0.046 ul/l) were a 10% decrease in total forage yield, a 19% decrease in clover yield, and a 19% increase in fescue yield compared to crops exposed to 0.028 ul/l of O3.
[Heagle AS et al; Phytopathology 79 (2): 128-36 (1989)]**PEER REVIEWED**

Groups of Fischer 344 male rats were exposed to 0.0, 0.12, 0.8, or 1.5 ppm ozone (O3) for 6 hr were killed immediately after and 3, 18, 42, or 66 hr after ozone exposure and their lungs were lavaged. Rats showed no clinical signs during whole-body exposure. Compared to sham-exposed (control) rats, exposure to 0.12 ppm O3 had no measurable effect on the total number, labeling index, mitotic index, or morphology of rat alveolar macrophages. The number of neutrophils was significantly greater than in controls at 3, 18, and 42 hr after exposure to 1.5 ppm O3, and 42 hr after exposure to 0.8 ppm. The number of pulmonary alveolar macrophages was approx twice that of controls 42 and 66 hr after exposure to 0.8 and 1.5 ppm O3. There was a significant incr in macrophage mitotic index 42 and 66 hr after exposure to 1.5 ppm, and 42 hr after 0.8 ppm O3. The incr in the number of pulmonary alveolar macrophages in mitosis was preceded by an increase in the labeling index. The labeling index was significantly greater than controls 18 and 42 hr after exposure but returned to near normal levels by 66 hr after exposure. There was a transient decr in the mean nuclear/cytoplasmic ratio of pulmonary alveolar macrohages from rats exposed to 1.5 ppm O3, 18 and 42 hr after exposure, due to an incr in the mean cytoplasmic area. Comparison of the macrophage population doubling time and cell cycle time suggest that proliferation played a significant role in the observed incr in macrophages following exposure to 0.8 and 1.5 ppm O3.
[Hotchkiss JA et al; Exp Lung Res 15: 1-16 (1989)]**PEER REVIEWED**

BALB/c mice were continuously exposed to 8.0 ppm ozone (O3) or nitrogen dioxide (4.0 ppm) plus O3 for 3, 7, 24, and 56 days. Organ wt (lung, thymus, and spleen) and antibody responses to sheep red blood cells, and to DNP-Ficoll were measured immediately after exposure. Lung wt in mice exposed to O3 or the mixture were incr significantly in all exposure periods. The wt of thymus and spleen in mice exposed for 3, 7, and 14 days to the mixture were decr. O3 exposure for 56 days caused significant decr of the wt of both organs. Antibody response to sheep RBC in mice exposed for 3, 6, or 14 days to O3 or the mixture was markedly suppressed, but exposure to the mixture for 56 days did not cause the suppression of anti-sheep RBC antibody response. No differences in anti-DNP antibody response between exposed and control mice were observed, except those exposed to O3 or the mixture for 14 days.
[Fujimaki H; Environ Res 48 (2): 211-7 (1989)]**PEER REVIEWED**

Cellular inflammatory responses in the nose and lung of rats were investigated by nasal and bronchoalveolar lavage and morphometric quantitation of neutrophils within the nasal mucosa and pulmonary terminal bronchioloalveolar duct regions. Rats were exposed to 0, 0.12, 0.8, or 1.5 ppm ozone for 6 hr and were sacrificed immediately or 3, 18, 42, or 66 hr following exposure. Rats exposed to 0.12 ppm ozone had no change in the number of neutrophils recovered from bronchoalveolar lavage fluid at any time after exposure; however, 18 hr after exposure, increased numbers of neutrophils (15 fold) as compared to controls were recovered from nasal lavage fluid. Rats exposed to 0.8 ppm ozone had more neutrophils (44 fold) in nasal lavage fluid than controls immediately after exposure, but no concomitant increase in bronchoalveolar lavage fluid neutrophils at that time. However, as the number of neutrophils in bronchoalveolar lavage fluid increased (maximum 42 hr), the number of neutrophils recovered from nasal lavage fluid decreased. Rats exposed to 1.5 ppm ozone had no significant increases in nasal neutrophils in lavage fluid at any time after exposure but had greatly increased numbers of neutrophils in bronchoalveolar lavage fluid 3, 18, and 42 hr after exposure.
[Hotchkiss JA et al; Toxicol Appl Pharmacol 98 (2): 289-302 (1989)]**PEER REVIEWED**

The influence of drought stress on foliar injury and yield responses of field grown cotton to ozone was studied. Cotton was grown on Hanford coarse sandy loam at three levels of soil water (optimal, suboptimal, and severely stressed) in open top chambers exposed to seasonal 12 hour ozone concentrations of 0.015, 0.074, 0.094, and 0.111 ul/l ozone. The experimental plot was located in Riverside, California. Foliar injury at ambient (0.074 ul/l) ozone concentrations were as follows: severely drought stressed cotton, 25%; moderately stressed plants, 56%; and optimally watered plants, 68%. Lint and seed yields were significantly reduced by ozone in optimally watered and suboptimally watered plots, while severely stressed cotton showed no yield reductions except at 0.111 ul/l. Yield reductions were primarily attributed to fewer bolls. Yield losses at ambient ozone concentrations relative to a background ozone level of 0.025 ul/l were predicted at 26.2% for optimally watered plants, 19.8% for suboptimally watered plants, and 4.7% for severely stressed plants.
[Temple PJ et al; Agron J 80 (4): 751-5 (1988)]**PEER REVIEWED**

Radish (Raphanus sativus) plants were fumigated with 0.1 or 0.05 ul/l ozone (O3) for 8 or 24 hr/day for 6 to 18 hr/day for 6 days. Ozone induced an incr in both the number and size of the plastoglobules but a decr in chloroplast dimensions. These changes in the chloroplasts developed further even after O3 fumigation had been discontinued. The plastoglobules were electron dense in the early stages of exposure to O3 but subsequently became electron translucent. Finally large plastoglobules were extruded into the vacuole, a phenomenon which may partly account for the reduction in chloroplast size. Ozone also caused disruption of the tonoplast followed by collapse of the cells. Low concn of O3 appeared to accelerate senescence of the chlorplasts.
[Miyake H et al; New Phytol 111 (2): 187-95 (1989)]**PEER REVIEWED**

Breathing pattern (frequency and tidal vol), minute ventilation, oxygen consumption (MO2), and rectal temperature were measured from male Sprague Dawley rats exposed to 0.8, 0.6, 0.4, and 0.2 ppm ozone (O3) to determine the relation between breathing pattern responses to O3 and metabolic rate. In 0.8 ppm O3, rapid shallow breathing began at 60 min exposure while minute ventilation and oxygen consumption declined beginning at 40 min. In comparison to clean air exposed animals, rats (n = 8) during the third hr of 0.8 ppm O3 exposure had a 27% incr in frequency, 35% decline in tidal vol, 20% decr in minute ventilation, 24% decr in oxygen consumption, and 1.3 deg C decr in rectal temperature. At lower O3 concn, responses were diminished in magnitude, and in rats exposed to 0.2 ppm O3, only oxygen consumption was significantly decr. Irritant induced depression of minute ventilation did not imply a state of hypoventilation or hypoxia because ventilation equivalent for O2 (minute ventilation/oxygen consumption) did not decline during O3 exposures.
[Mautz WJ, Bufalino C; Respir Physiol 76 (1): 69-78 (1989)]**PEER REVIEWED**

Alfalfa (cv WL-514) was grown in 30, 3 by 5.5 m plots on Wasco sandy loam (coarse loamy, mixed, nonacid, thermic Typic Torriorthents) in Shafter, CA and was exposed in open top chambers to five levels of O3 for 12 hr daily, from March to October of 1984 and 1985. Ozone treatments ranged from charcoal filtered air to twice ambient O3 concn. Seasonal 12 hr O3 concn for the Apr to Oct growing season averaged 0.049 ul/l in 1984 and 0.042 ul/l in 1985. Each plot received either normal amounts of irrigation or 30% less than normal. Ozone significantly reduced canopy temp/air temp differentials by 31% in normally irrigated plots and 37% in water stressed plots in 1984, but not in 1985. Water use, rate of soil water depletion, or depth of effective rooting zone were not affected by O3. Water use efficiency was significantly reduced by O3, averaging 12% lower in nonfiltered compared with charcoal filtered plots. The effects of O3 on water use efficiency were attributed to premature senescence and abscission of older alfalfa leaves.
[Temple PJ, Benoit LF; Agron J 80 (3): 439-47 (1988)]**PEER REVIEWED**

Adult male Charles River CD rats were exposed to 1 ppm (1.96 mg/cu m) ozone or air for 2 wk. The ozone exposed animals had significantly heavier lungs, and greater lung wt/body wt ratios, than controls as early as 3 days from the onset of exposure, which persisted throughout the exposure period. At 3, 5, 7, or 14 days after the onset of exposure, samples of plasma and lung lavage were obtained. All samples were tested against purified preparations of fetal rat lung fibroblasts. Heat inactivated plasma, from animals exposed to ozone for 7 or 14 days, significantly increased DNA synthesis by lung fibroblasts compared with plasma from air exposed animals. Fractionation of plasma and lavage samples indicated that the factor responsible had an isoelectric point of 6.45 to 6.75 and a molecular weight of 32 + or - 2 kDa. This factor had a dose dependent effect on lung fibroblast DNA synthesis in culture, but no significant effect on cultured pneumocyte DNA synthesis. The factor was detectable within 72 hr of exposure.
[Tanswell AK et al; J Toxicol Environ Health 27 (2): 239-54 (1989)]**PEER REVIEWED**

Male Wistar rats were continuously exposed to 0.2 ppm ozone for 14 days. Alveolar macrophages were collected at intervals by bronchoalveolar lavage to examine the effects of ozone. The specific activities of glucose-6-phosphate dehydrogenase and glutathione peroxidase of alveolar macrophages increased to 1.6 fold (on the third day) and 1.5 fold (on the fifth day), respectively, compared to control values. The specific activities of pyruvate kinase, lactate dehydrogenase, and hexokinase also increased 1.6 fold, 1.4 fold, and 1.2 fold, respectively, on the third day. The activities of all enzymes tested were maintained at significantly higher levels until the 14th day. The incorporation of (14)C labeled thymidine into alveolar macrophages increased the control values two fold on the first and third days and was almost completely inhibited by the addition of 1.23X10-4 M aphidicholgine, a competitive inhibitor of DNA polymerase alpha. The number of alveolar macrophages collected from exposed animals also increased to 1.5 times that of the control on the third day and was maintained at a significantly higher level until the 14th day. Alveolar macrophages of a small size preferentially increased between the fifth and 14th days.
[Mochitate K, Miura T; Environ Res 49 (1): 79-92 (1989)]**PEER REVIEWED**

A mathematical formulation was derived that describes the transport and chemistry of atmospheric gases as they diffuse through the open stomata, inner air spaces, and cell walls of plant leaves before depositing on the mesophyllic plasmalemma. The formulation was applied to the problem of ozone deposition on plant leaves to determine whether reactions in the mesophyllic cell wall water can prevent ozone from reaching the plasmalemma and initiating harmful oxidation reactions. Calculations indicate that a major portion of the ozone diffusing through the leaf can react with ascorbic acid in the cell wall. Other mechanisms such as ozone reactions with biogenic olefins and ozone decomposition in the cell wall water were found to be unimportant.
[Chameides WL; Environ Sci Technol 23 (5): 595-600 (1989)]**PEER REVIEWED**

Following exposure of male Sprague Dawley rats to 2 ppm ozone for 4 hr, lung inflammatory cells were harvested by serial bronchoalveolar lavage. At 2 hr postexposure, a decr (p < 0.05) in lavagable inflammatory cells was noted from a mean control value of 3.8X10+6 to 2.2X10+6 cells/rat. By 72 hr postexposure, an incr (p < 0.05) in lavagable cells was observed which remained above control values for up to 7 days following the exposure. Two distinct effects on rat lung inflammatory cell oxidant generation were observed. Opsonized zymosan and 12-O-tetradecanoylphorbol-13-acetate stimulated O3 production by the inflammatory cell population was found to be maximally inhibited 24 hr following ozone exposure (47 and 57% of controls, respectively, p < 0.05). In contrast, luminol amplified chemiluminescence increased 24 hr following ozone exposure, coinciding with an incr in the percentage of neutrophils (26 + or - 3% vs 0.1% in controls) and myeloperoxidase (0.521 + or - 0.075 vs 0.002 units/1x10+6 cells in controls) in the inflammatory cell population. Supporting the involvement of myeloperoxidase in the enhanced oxidant generating status of these cells, the luminol amplified chemiluminescence was found to be azide (100 uM) inhibitable (80% inhibition, p < 0.5), but not superoxide dismutase (300 ug/ml) inhibitable. Additionally, this cell population was found to generate taurine chloramines, a myeloperoxidase dependent function which was absent prior to the ozone exposure and also demonstrated enhanced activation of benzo(a)pyrene-7,8-dihydrodiol to its light emitting dioxetane intermediate. Addition of myeloperoxidase to control alveolar macrophages resulted in enhanced luminol amplified chemiluminescence, taurine chloramine generation, and enhanced chemiluminescence from benzo(a)pyrene-7,8-dihydrodiol.
[Esterline RL et al; Toxicol Appl Pharmacol 99 (2): 229-39 (1989)]**PEER REVIEWED**

Beech (Fagus sylvatica leguminosae) and ivy (Hedera helix leguminosae) plants, as well as isolated cuticles of the adaxial leaf surfaces of Citrus aurantium leguminosae, Ficus elastica Roxb. var. decora and Hedera helix leguminosae, were exposed to environmentally realistic ozone concn (up to 130 nl/l) in combination with acid fog (pH 3.0) for several mo. Isolated Citrus, Ficus and Hedera cuticles and cuticles isolated from adaxial leaf surfaces of Ilex aquifolium leguminosae and Prunus laurocerasus leguminosae and from fruits of Capsicum annuum leguminosae and Lycopersicon esculentum Mill. were fumigated with 2.5% (vol/vol) ozone for 1 or 2 hr in dry and moist conditions, respectively. The water permeance of the non-isolated cuticles of the astomatous adaxial leaf sides of beech and ivy and of the isolated cuticles was not altered by exposure to a realistic ozone stress. Fumigation with very high ozone concn decr water permeance of isolated Ficus and Hedera cuticles by about 20% and incr water permeance of all other isolated cuticles by up to 200% (Capsicum). In some cases the 2 hr fumigation under moist conditions had no significant effect upon water permeance.
[Kerstiens G, Lendzian KJ; New Phytol 112 (1): 21-7 (1989)]**PEER REVIEWED**

Nine day old spring barley (Hordeum vulgare cv Klaxon) plants were exposed to 0.05, 0.10 or 0.15 ul/l ozone for 12 days. Fumigation was administered for 7 hr between 9.00 hr and 16.00 hr each day. Using conventional IRGA equipment, the carbon dioxide exchange rate was found to decrease with increasing concentration of ozone during the exposure period, falling to 60% of the control value at the highest ozone concentration. Transpiration rates and stomatal conductance showed similar trends. Light saturation curves, obtained using a leaf disc oxygen electrode, demonstrated that ozone treated leaves had lower apparent quantum yields and generally lower rates of ozone evolution at saturating light and carbon dioxide levels. Oscillations in chlorophyll and fluorescence, normally observed in control plants, could not be detected after ozone treatment and could only be restored to some extent by feeding the phosphate sequestering agent D-mannose to the leaves.
[Rowland-Bamford AJ et al; Environ Pollut 59 (2): 129-40 (1989)]**PEER REVIEWED**

Picea sitchensis (Bong) Carr (Sitka spruce) and Picea abies Karst (Norway spruce) were grown in controlled environments and then exposed to ozone for short periods as in mid-afternoon episodes experienced in the forest. For concentrations between 20 and 300 nl/l there was a linear relationship between exposure concentration and ozone uptake rates. Increasing photon flux densities increased rates of photosynthesis and transpiration, the increases being larger in actively growing than in dormant seedlings. Physiological condition (dormancy or active growth), species and photon flux density were found to influence ozone flux via their effects on stomatal conductance. Exposure to 80 nl/l ozone resulted in consistent increases of stomatal conductance and there were also indications that water use efficiency was decreased.
[Freer-Smith PH, Dobson MC; Environ Pollut 59 (2): 161-76 (1989)]**PEER REVIEWED**

Male Fischer 344 rats exposed to ozone O3 (0, 0.35, 0.5, or 1.0 ppm) for 2.25 hr for 5 consecutive days showed an increased frequency of breathing and a decr tidal volume on Days 1 and 2 of exposure at all O3 concn. However, by Day 5 these breathing responses to O3 were diminished in rats exposed to 0.35 and 0.5 ppm, but not in rats exposed to 1.0 ppm. In addition, a flow limitation in smaller airways was observed after the second day of exposure to 0.5 ppm O3 that initially attenuated and then disappeared by the fifth day of exposure. In contrast to these findings, a light microscopic examination of mixed lung tissue sections from rats exposed to 0.5 ppm indicated a 5 day progressive pattern of epithelial damage and inflammation in the terminal bronchiolar region. Maximal tissue damage occurred on Days 4 and 5 of O3 exposure. A sustained 37% incr in lavageable protein was also observed over the course of the 5 day exposure regimen to 0.5 ppm. Lung glutathione increased initially, but it was within the control range on Days 4 and 5. Lung ascorbate was significantly elevated above control levels on Days 3 and 5.
[Tepper JS et al; Am Rev Respir Dis 140 (2,1): 493-501 (1989)]**PEER REVIEWED**

Loblolly pine seedlings were planted in a sandy loam soil having approx 15 or 35 mg/kg magnesium (Mg) and were exposed to subambient (0.02 ul/l), ambient (0.04 to 0.05 ul/l), or twice ambient (0.07 to 0.09 ul/l) concn of ozone (O3) in open top chambers from May through Oct. Seedlings also received ambient amounts of simulated rainfall at pH 3.8 or 5.2. Root biomass, length, and branching frequency were not significantly affected by O3, rainfall acidity, or soil Mg treatments. Seedlings grown in the subambient O3 treatment had a greater (but not significant) number of short roots infected with mycorrhizae than seedlings grown in ambient or twice ambient O3 treatments. Significant O3/pH/Mg interactions were detected. At the high pH, biomass and length were greatest for seedlings exposed to ambient O3 levels, and least for seedlings exposed to twice ambient O3 levels. For both soil Mg treatments, seedlings exposed to subambient O3 levels exhibited an incr in the number of Type B mycorrhizal short roots associated with incr pH of the rainfall treatments, with the largest differences between pH treatments observed for seedlings grown in the low Mg soil. In contrast, the number of Type B mycorrhizal roots on seedlings exposed to ambient or twice ambient O3 levels decr as the pH of the rainfall treatments increased from 3.8 to 5.2.
[Simmons GL, Kelly JM; Water Air Soil Pollut 44 (1-2): 159-71 (1989)]**PEER REVIEWED**

Groups of 15 field grown strawberry plants (Fragaria x ananassa Duch. Chandler) were exposed to simulated fog (pH 7.24, 2.69, or 1.68) twice weekly for 11 wk, singly or in combination with ambient levels of ozone in open top field chambers. Plants grown in ambient 03 (whole study 12 hr avg of 66 ppb) exhibited no significant alterations in growth, but yields were higher than in plants exposed to charcoal filtered air (19 ppb O3). Exposure to ambient 03 induced significant depressions in leaf gas exchange on a unit leaf area basis (i.e. net photosynthesis, stomatal conductance of water vapor, and transpiration), but calculated whole plant photosynthesis was similar in charcoal filtered air and O3 exposed plants due to differences in leaf area per plant (i.e. 14% higher in 03 exposed plants). No significant (fog chemistry x air quality) effects were found for any of the measured growth or yield parameters.
[Takemoto BK et al; Environ Exp Bot 29 (3): 379-86 (1989)]**PEER REVIEWED**

Tomato (Lycopersicon esculentum Mill.) 'New Yorker' plants were exposed to 0.16 ul/l ozone (O3) for 1 hr during early vegetative stage and pre-floral stage, during different leaf growth stages. Leaf growth stages studied were young expanding leaf, 80% expanded, 95% expanded, fully expanded and fully expanded leaf plus 1 day. The leaf diffusive conductance varied among leaf growth stages and between plant development stages and leaf surfaces; there was no continuity in the leaf diffusive conductance pattern. Sorption rates differed among some leaf growth stages, and between plant development stages in expanding leaves (growth stage 1). Expanding leaves of early vegetative plants sorbed more ozone than expanding leaves of pre-floral plants (0.05 < p < 0.10). For both development stages, high sorption rates occurred in fully mature leaves; otherwise little similarity between corresponding leaf growth stages was evident. No visual injury was observed on plants at the early vegetative development stage whereas visual injury occurred on the pre-floral development stage plants. Some leaf growth stages developed more injury than others. Total O3 flux to the leaf was not well predicted by the leaf diffusive conductance for water vapor; nor was visible injury well related to total flux.
[Graham S, Ormrod DP; Environ Pollut 58 (2-3): 213-20 (1989)]**PEER REVIEWED**

4 yr old Norway spruce clones (Picea abies) were cultivated in sand and provided with a complete nutrient solution including 30 mg magnesium (Mg) and 90 mg calcium (Ca)/season/plant, or a solution deficient in magnesium and calcium (20% of above Mg and Ca, during 2nd season only). Groups of 8 plants (4 normal and 4 Ca/Mg deficient) were exposed to 1 of 2 pollutant mixtures: 150 ug/cu m ozone (O3) with 75 ug/cu m nitrogen dioxide (NO2); and 50 ug/cu m O3 with 75 ug/cu m sulfur dioxide and 75 ug/cu m nitrogen dioxide for 32 wk (during 2nd season). Total nitrogen (N) content of current yr and 1 yr old needles lay below 11 to 13 mg/g dry wt. Fumigation caused a 20% (nonsignificant) incr of total nitrogen (N) content in current yr needles, whereas in 1 yr old needles N concn did not change. The response of nitrate reductase activity to pollutant stress depended on needle age and nutrient supply, respectively. In 1 yr old needles fumigation resulted in a significant (p < 0.05) inhibition of enzyme activity, particularly in Mg and Ca deficient trees. The combination of all 3 components proved to be most effective in causing a decr by 60% in Mg and Ca deficient plants compared to the control. In contrast, nitrate reductase activity was stimulated in current yr needles by both O3/NO2 and O3/SO2/NO2.
[Klumpp A et al; Environ Pollut 58 (4): 261-71 (1989)]**PEER REVIEWED**

The native ground vegetation of a beech forest near Giessen, FRG, was fumigated with 300 ug/cu m sulfur dioxide (SO2), 100 ug/cu m nitrogen dioxide (NO2), and 200 ug/cu m ozone (O3) in open top chambers (1 sq m) for 4 hr per wk from Mar/Apr through Oct. Twenty seven Melico-Fagetum allietosum plots with Allium ursinum leguminosae (broad leaved garlic) as the dominating species were used; 9 were controls, 9 exposed to SO2 + NO2, and 9 exposed to SO2 + NO2 + O3. 3 additional plots were fumigated to SO2 and NO2 for 16 hr and O3 for 16 hr (9.00 to 17.00 on 2 consecutive days) weekly. The effects of O3 on growth and above ground development were dependent on species. Fumigations with all 3 pollutants caused a decr of absolute leaf area index of 51 and 90% below the control values for Allium ursinum at the second and third recording in 1986, respectively. Treatments caused early senescence in several of the species present. The epicuticular waxes were attacked by fumigation, which was shown by higher wettability of the leaf surfaces and by leaching of ions. In Allium ursinum, 5 weekly treatments for 4 hr each led to a higher wettability. Interspecific differences were observed in the responses of transpiration and photosynthesis to fumigation. Similar patterns of effects on transpiration and photosynthesis, however, were found in the same species. In Allium ursinum, transpiration was depressed significantly. Carbohydrate metabolism was altered by fumigation, leading to starch accumulation in the leaves. Starch content of Allium ursinum leaves were significantly incr in relation to controls. Besides effects on higher plants, fumigations also resulted in reduction of the soil microflora. The bacteria/fungi ratio was also depressed at the fumigation plots.
[Steubing L et al; Environ Pollut 58 (4): 281-302 (1989)]**PEER REVIEWED**

The individual and combined impacts of acidic precipitation, ozone and soil magnesium (Mg) status on nutrient concn of throughfall, soil solution, soil, and seedling components were evaluated after one growing season. Loblolly pine seedlings were planted in a sandy loam soil having approx 15 or 35 mg/kg exchangeable Mg and were exposed to subambient (charcoal filtered air, 0.02 O3 ul/l), ambient (0.04 O3 ul/l), or twice ambient (0.07 O3 ul/l) concn of O3 in open top chambers from May though Oct. Seedlings also received ambient amounts of simulated precipitation at pH 4.0 or 5.3 during this period. Ozone treatments had no significant effects on tissue nutrient concn or soil solution chemistry. O3 did not significantly affect the concn of nitrogen, sulfur, phosphorus, potassium, calcium or magnesium Mg in any plant component. Interaction responses were very limited and do not suggest any significant synergisms.
[Simmons GL, Kelly JM; Water Air Soil Pollut 43 (1/2): 199-210 (1989)]**PEER REVIEWED**

In Jun through Oct 1986 afield expt (Raleigh, NC) was performed with soybean to test the influence of periodic water stress on the yield response to ozone (O3). Open top field chambers were used to expose plants to a range of O3 concn, and rain exclusion caps were used on individual chambers to help regulate soil moisture levels. Mean seasonal 12 hr/day O3 concn avg 0.018 (charcoal filtered air), 0.038 (ambient air), 0.059, 0.071, and 0.085 ul/l. Three soil moisture treatments were used: well watered (WW), water stressed (WS), and well watered with permanent rain exclusion caps that were in place from 35 days after planting until physiological maturity (WWC). In the well watered and water stressed treatments, the rain caps were put in place only during an exceptionally wet period from mid Aug to mid Sept. Visible injury to the 8 uppermost mainstem leaves was usually greater as O3 concn incr in all soil moisture treatments. Ozone effects on the number of filled pods, wt of filled pods, number of seeds, wt of 100 seeds, and seed yield were significant in the analysis of variance. The well water and well water capped treatments had approx the same yield and response to O3, indicating that the presence of caps for most of the growing season had little effect on growth or sensitivity to O3. WS plots yielded approx 10% less on the avg than the well water and well water capped plots, but water stress did not change the response to O3 (eg, no significant O3 x water interaction). Based on a Weibull dose response model, O3 reduced the yield of soybean 13% at a concn of 0.05 ul/l (12 hr/day seasonal mean) compared to a hypothetical background of 0.02 ul/l.
[Miller JE et al; J Environ Qual 18 (3): 330-6 (1989)]**PEER REVIEWED**

A 4.66 m diameter, 3.6 m tall cylindrical open top field chamber was designed, constructed, and tested as a tool to measure the effects of air quality on plant function and yield. The chamber has an aluminum channel frame covered with clear polyvinyl chloride plastic film. It is equipped with a frustum (truncated cone) that decr ambient air ingress and can be fitted with a device to exclude rain (rain cap) for studies with simulated rain pH. During the daylight hr, the mean air temperature within the chamber was 0.6 C greater than ambient on cloudy, cold days, 2.2 C greater than ambient on partly cloudy, cool days, and 2.8 C greater than ambient on sunny, warm days. The mean dew point temp for a wide range of conditions was 0.7 C greater inside than outside. Mean solar radiation in the chamber, with new plastic panels, was 15% less than ambient with a rain cap and 12% less with no rain cap. Charcoal filtration removed 78% of the ozone (O3) in ambient air; long term measurements during charcoal filtration showed that the mean O3 concn in the chamber (all positions and heights) was 77% less than ambient (0.010 vs 0.047 ul/l during 12 days), suggesting little or no long term ingress through the top. Short term gradients in O3 concn existed (mostly near the top of the chamber) during infrequent periods of strong winds. During addition of approx 0.09 ul/l of O3 to nonfiltered air, the mean (14 day) O3 concn across all positions and heights (n = 15) varied by less than 0.005 ul/l of the overall mean.
[Heagle AS et al; J Environ Qual 18 (3): 361-8 (1989)]**PEER REVIEWED**

Differences in the ozone (O3) sensitivity of five commonly grown cultivars of white clover, namely Ladino Sacramento, Ladino California, Alban, Sonja and Milkanova, were studied in Switzerland. Plants were grown in pots and exposed to O3 using three different exptl systems: (i) exposure to ambient air (ca 72 ug/cu m), (ii) exposure in open top chambers to filtered air, unfiltered air, or unfiltered air to which O3 was added from 09.00 until 17.00 hr during a 4 day period, (iii) exposure under controlled environmental conditions to filtered air with or without O3 added daily. Occurrence of injury symptoms on field grown plants was recorded during the summers of 1987 and 1988. Ozone exposure produced visible injury expressed as small necrotic flecks on the upper leaf surface. 36 to 65% of the plants exhibited signs of injury in 1987 and 10 to 48% in 1988 field studies. Irrespective of the exptl system used, the following order in O3 sensitivity was observed: leguminosae Sacramento > leguminosae California >> Alban > Sonja > Milkanova. Injury symptoms were seen when plants were exposed to ambient O3 or to unfiltered air in open top chambers, but not in charcoal filtered air. In ambient air, symptoms in the most sensitive cultivars appeared after episodes with 1 hr max concn of above 120 to 140 ug/cu m occurring on several consecutive days. The symptoms of injury could be reproduced in controlled environment fumigation expt using concn comparable to those observed in ambient air. Plants of the different cultivars grown under controlled environmental conditions did not differ in superoxide dismutase or peroxidase activity, or in the content of fructose, sucrose or glucose. Differences in O3 sensitivity between cultivars were related to differences in stomatal density and to some degree to the length of the stomatal pore. Stomatal densities were related to leaf conductance, transpiration, and rate of water loss by excised leaves. Leaves of Milkanova (resistant) had higher delta(13)C values than leguminosae California (sensitive). Compared with filtered air, exposure to unfiltered ambient air or O3 amended air in open top chambers caused a change in the delta(13)C value in leaves of leguminosae California (sensitive), but not in leaves of Milkanova (resistant).
[Becker K et al; New Phytol 112 (2): 235-43 (1989)]**PEER REVIEWED**

Alnus serrulata (Aiton) Willdenow seedlings with and without root nodules formed by the nitrogen-fixing actinomycete Frankia were exposed to clean filtered air or ozone (O3) at 0.12 ul/l, 4 to 11 hr/day for 27 days (approx 164 hr total exposure). Gas exchange measurements on leaves and transmission electron micrographs of root nodule cells were made to detect any O3 effects on the functioning of leaves and the root symbiont. Photosynthesis, stomatal conductance, and internal CO2 concn were calculated for all plants in clean O3- free air more than 3 wk after the fumigations began. Significant positive correlations between photosynthesis and stomatal conductance were found for leaves of control nodulated and unnodulated alders and O3-treated nodulated alders. There was a weak positive correlation between photosynthesis and conductance for unnodulated O3-treated seedlings measured in clean air. When O3- treated leaves were measured during fumigation with O3, no positive correlation between photosynthesis and conductance was found for either nodulated or unnodulated seedlings. Photosynthetic rates of leaves having the highest stomatal conductance values were decr by O3 for both nodulated and unnodulated plants. Transmission electron microscopy revealed that after a 27-day exposure of shoots to O3, host root cells of nodules from O3-treated plants lacked organelles and showed extensive cytoplasmic breakdown. Hyphae and nitrogen-fixing vesicles of Frankia appeared normal. The Frankia endophyte seems to be more resistant to O3 than is the host root nodule cell.
[Greitner CS, Winner WE; New Phytol 111 (4): 647-56 (1989)]**PEER REVIEWED**

The potential for developing intraspecific lines of radish based on their relative resistance to either ozone (O3) or sulfur dioxide (SO2) was examined using growth analysis techniques. Plants were exposed to either 0.10 ul/l O3 or 0.50 ul/l SO2 for 4 hr/day, 3 days/wk, for 3 wk. Resistant and sensitive individuals were then selected and divided into four groups: O3 resistant (O3R), O3 sensitive (O3S), SO2 resistant (SO2R), and SO2 sensitive (SO2S). Cross-pollinations were made among plants within the selected groups and seed collected. F1 populations were raised from the resulting seed and exposed to the same exposure regime. Net photosynthesis and stomatal conductance were measured during the final two fumigations, and plants were harvested immediately following the final exposure, divided into component parts, dried and weighed. O3 and SO2 generally caused biomass reductions in all the F1 groups. O3 reduced below ground growth more than SO2, leading to greater reductions in root/shoot ratios. O3 resistant plants were resistant to both pollutants, showing little biomass reduction particularly from O3. Root/shoot ratios of these plants were altered less by pollutant exposure than non-selected radishes. Shoot growth of SO2 resistant plants was greater in O3 or SO2 than non-selected plants, but below ground growth was similar. Selection for plants sensitive to either pollutant was not apparent from growth analysis, as growth of the sensitive plants was generally the same as that of non-selected plants. Gas exchange results indicated greater stomatal conductance in O3 sensitive plants in filtered air than either non-selected or O3 resistant plants, while O3 resistant plants had lower conductance rates in the O3 treatment.
[Gillespie CT, Winner WE; New Phytol 112 (3): 353-61 (1989)]**PEER REVIEWED**

Models of rat lung injury, based on acute exposure to 2 ppm ozone for 3 hr and on exposure to 0.85 ppm ozone for 2 days, were used to determine whether N-(2-(2-oxo-1-imidazolindinyl)ethyl)-N'-phenylurea pretreatment of rats protected lungs from oxidant injury. Rats were pretreated with 100 mg/kg body wt N-(2-(2-oxo-1-imidazolindinyl)ethyl)-N'-phenylurea by ip administration for 2 days prior to and on the days of ozone exposure. No adverse toxicological effects of N-(2-(2-oxo-1-imidazolindinyl)ethyl)-N'-phenylurea pretreatment were observed. Lung superoxide dismutase and catalase activities were significantly enhanced from 636 to 882 U/lung and from 599 to 856 U/lung, respectively. One day following acute exposure (2 ppm for 3 hr), an ozone-induced incr of polymorphonuclear leukocytes (PMNs) from 0.01 to 1.18 million cells/lung was decr to 0.68 million by N-(2-(2-oxo-1-imidazolindinyl)ethyl)-N'-phenylurea pretreatment. No alteration occurred in the degree of lung permeability indicated by incr lavage fluid albumin. N-(2-(2-oxo-1-imidazolindinyl)ethyl)-N'-phenylurea pretreatment also significantly decr ozone-induced incr in polymorphonuclear leukocyte recovery after 2 days exposure to 0.85 ppm ozone from 5.54 to 2.12 million cells/lung. However, in this second case, N-(2-(2-oxo-1-imidazolindinyl)ethyl)-N'-phenylurea pretreatment reduced the observed ozone damage, indicated by a decr in lavage fluid albumin and by a decr in the macrophage and lymphocyte infiltration associated with this length of ozone exposure.
[Bassett DJP et al; Toxicol Appl Pharmacol 100 (1): 32-40 (1989)]**PEER REVIEWED**

Four cultivars of bean,with different sensitivities to ozone (O3), were exposed to chronic doses of O3 for 7 hr/day in early (0.058 ppm O3) and late-season (0.055 ppm O3) studies. The 7 hr/day seasonal O3 treatment means for the carbon filtered, non filtered, nonfiltered + 0.04 ppm O3, and nonfiltered + 0.08 ppm O3 groups in the early study were 0.035, 0.050, 0.087, and 0.119 ppm, respectively. The same treatment values for the late study were 0.026, 0.045, 0.087, and 0.126 ppm, respectively. Plants were pot cultured in open top field chambers. Greater than ambient O3 doses were applied by supplementing the O3 present in nonfiltered air with additional O3 at a constant rate for 7 hr/day. Cultivar sensitivity, as determined using an acute exposure screening protocol, was maintained in both studies. Regression of yield against O3 concn showed that Bush Blue Lake-254 and Bush Blue Lake-290 were more sensitive to O3 than were Bush Blue Lake-274 and Dwarf Horticultural bean plants. Foliar injury was significantly correlated with yield and biomass parameters. In the early study, the effects of O3 on tops and roots were similar for each cultivar, whereas in the late study, the root growth was more sensitive than top growth in 3/4 cultivars. Pod number and dry wt yields of sensitive cultivars in response to O3 were clearly different from those of resistant cultivars. Predicted relative yield suppression at a 7 hr/dayseasonal mean of 0.04 to 0.06 ppm (the common ambient range in eastern US) was 2% to 4% for the 2 resistant cultivars and 10% to 26% for the 2 sensitive cultivars.
[Heck WW et al; J Am Soc Hort Sci 113 (1): 46-51 (1989)]**PEER REVIEWED**

Rats exposed to up to 1.97 ppm during parts or all of organogenesis produced no defects in the offspring.
[Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986. 436]**PEER REVIEWED**

Blepharophimosis and jaw anomalies /were observed/ in mouse fetuses exposed to utero to 0.02 ppmfor 7 hr five days a wk.
[Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986. 436]**PEER REVIEWED**

High concentrations have caused death in animals by lung congestion.
[Armour, M.A. Hazardous Laboratory Chemicals Disposal Guide. Boca Raton, FL: CRC Press Inc., 1991. 269]**PEER REVIEWED**

A single exposure of pollen of Brassica napus Tapidor or Libravo to 100 nl/l ozone either in vitro or in vivo on the anthers of intact plants had no significant effect on either pollen germination or pollen tube growth.
[Bosac C et al; New Phytol 124 (3): 439-46 (1993)]**PEER REVIEWED**

Two cultivars of watermelon (Citrullus lanatus) and muskmelon (Cucumis melo), which are widely grown in Spain, were exposed to ozone (70 nl/l, 6 hr/day) for 21 days. Ozone sensitivity was assessed by recording the extent of visible injury, changes in fast-fluorescence kinetics, the relative growth rate of root, and shoot, and effects on the number of flowers produced per plant. Leaf gas exchange was measured to provide some indication of the factors underlying differential response to ozone. After 9-10 days of fumigation, all the cultivars developed typical visible symptoms of ozone injury on the older leaves. However, significant (p < 0.05) changes in fast-fluorescence kinetics were detected prior to the development of visible foliar injury, indicating that detectable effects of ozone on primary photochemical processes supersede the appearance of visible symptoms. In both muskmelon and watermelon, there was a marked reduction in the rate of CO2 assimilation as a result of exposure to ozone, and this was accompanied by a parallel decrease in stomatal conductance. Mean plant relative growth rate was markedly (p < 0.01) suppressed by ozone in the two cultivars of watermelon, but there were no significant effects on R in muskmelon. Ozone reduced root growth relative to the shoot in three out of four cultivars. Moreover, exposure to ozone reduced flower production in both muskmelon and watermelon, which indicated effects on yield. There was no correlation between a variety of methods used to assess ozone sensitivity and visible injury. This observation draws clear attention to the dangers in ranking plants for ozone sensitivity purely on the basis of visible symptoms.
[Fernandez-Bayon JM et al; Environ Pollut 81 (3): 199-206 (1993)]**PEER REVIEWED**

Acetylcholine released from vagal nerve endings constricts airways by stimulating M muscarinic receptors on the airway smooth muscle. At the same time, released acetylcholine feeds back onto inhibitory M2 muscarinic autoreceptors on the nerve endings, limiting further release of acetylcholine. Loss of function of these M2 receptors increases vagally-mediated bronchoconstriction after viral airway infections, exposure to ozone, or antigen inhalation. Inflammation appears to be critical in the loss of M2 receptor function after ozone exposure.
[Fryer AD, Jacoby DB; Life Sci 52 (5-6): 529-36 (1993)]**PEER REVIEWED**

Ozone exposurein vivo has been reported to degrade arachidonic acid in the lungs of rodents. To study the chemical nature and biological activity of ozone exposed arachidonic acid, arachidonic acid in a cell-free, aqueous environment was exposed to air, 0.1 ppm ozone, or 1.0 ppm ozone for 30-120 min. arachidonic acid exposed to air was not degraded. All ozone exposures degraded > 98% of the arachidonic acid to more polar products, which were predominantly aldehydic substances and hydrogen peroxide. The type and amount of aldehydic substances formed depended on the ozone concn and exposure duration. A human bronchial epithelial cell line (BEAS-2B, S6 subclone) exposed in vitro to either 0.1 ppm or 1.0 ppm ozone for 1 hr produced arachidonic acid derived aldehydic substances, some of which eluted with similar retention times as the aldehydic substances derived from ozone degradation of arachidonic acid in the cell-free system. In vitro, ozone degraded arachidonic acid induced an increase in human peripheral blood polymorphonuclear leukocyte polarization, decreased human peripheral blood T-lymphocyte proliferation in response to mitogens, and decreased human peripheral blood natural killer cell lysis of K562 target cells. The aldehydic substances, but not hydrogen peroxide, appeared to be the principal active agents responsible for the observed effects. ozone-degraded arachidonic acid may play a role in the polymorphonuclear leukocyte influx into lungs and in decreased T-lymphocyte mitogenesis and natural killer cell activity observed in humans and rodents exposed to ozone.
[Madden MC et al; Environ Health Perspect 101 (2): 154-64 (1993)]**PEER REVIEWED**

Peritoneal macrophage from mice and isolated hepatocytes from rats were exposed to ozone. Ozone dosages were expressed as 0-5 nmol/10(6) cells. Measurements were made of viability, glucose transport, glutathione, glyceraldehyde-3-phosphate dehydrogenase, Mg-ATPase, Na/K-ATPase, and lipid synthesis. The most sensitive parameter was glyceraldehyde-3-phosphate dehydrogenase in the peritoneal macrophage. In hepatocytes both lipid synthesis and glyceraldehyde-3-phosphate dehydrogenase were sensitive to ozone. Effects on viability, glucose transport, Mg-ATPase, and Na/K-ATPase were small to negligible in both cell types.
[Peters RE et al; Toxicol Lett 69 (1): 53-61 (1993)]**PEER REVIEWED**

Rats carrying minipumps filled with 5-bromo-2'deoxyuridine were exposed to ozone, nitrogen dioxide, or a mixture of the two gases using four different protocols: (A) ozone 0.2 ppm, nitrogen dioxide 3.6 ppm, or their mixture for 24 hr a day; (B) ozone 0.2 ppm, nitrogen dioxide 7.2 ppm, or their mixture for 12 hr per night; (C) ozone 0.6 ppm, nitrogen dioxide 10.8 ppm, or their mixture for 8 hr per night; and (D) ozone 0.8 ppm, nitrogen dioxide 14.4 ppm, or their mixture for 6 hr per night. After three consecutive daily exposures, the animals were returned to filtered air. Seven days after implantation of the minipump, alveolar labeling indices were comparable to control values except in the group of animals exposed for 6 hr nightly to a combination of 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Labeling indices in the peripheral airways were the most sensitive exposure index since they were significantly increased over control values in all animals exposed to ozone, nitrogen dioxide, or a mixture of the two gases, regardless of concn or exposure duration. Labeling indices increased with elevated dose rate, eg, concn of the gases in the inspired air. The response to the combined gases was greater than the calculated sum of the responses to the two individual gases for the three higher dose rates in the large airways and for the highest dose rate in the peripheral airways. The results led to the following conclusions: (1) By the criterion of analysis of cell kinetics in rat large and peripheral airways, neither ozone, nitrogen dioxide, nor their mixture follows Haber's law (c x t = k) over the concn ranges studied; and (2) at the higher dose rates studied, there is a more than additive (synergistic) airway response to the combination of ozone and nitrogen dioxide.
[Rajini P et al; Toxicol Appl Pharmacol 121 (2): 186-92 (1993)]**PEER REVIEWED**

Controlled environment facilities were used to determine the growth response of hybrid poplar using concn and exposure frequencies of ozone that mimic ambient patterns. Young cuttings of Populus deltoidesigra were exposed to daily bell-shaped concn profiles of ozone with four peak concn and two exposures per week for 1 to 4 weeks. Exposure to ozone initially stimulated height growth rate, but repeated exposure resulted in decreases in height growth rate. Stem diameter growth rate decreased with increasing ozone concn. Leaf greenness decreased with repeated exposure. The rate of leaf production declined with increasing ozone concn. Many leaves abscised in the higher ozone treatments, resulting ultimately in stimulation of bud break. Leaf area, leaf dry weight, and root dry weight at harvest decreased with increasing total ozone exposure regardless of number of exposures. Stem dry weight was greater after limited initial ozone exposure but was less after repeated ozone exposures. Repeated exposures to ozone were uniformly detrimental to poplar growth parameters.
[Tenga AZ et al; Can J For Res 23 (5): 854-8 (1993)]**PEER REVIEWED**

Oxygen and ozone both have been found to enhance or to inhibit the development of tumors in mouse lung. As a general rule, preexposure to the oxidant, before administration of a carcinogen, or exposure to high levels for a comparatively short time immediately following carcinogen administration favors development of tumors. On the other hand, prolonged exposure begun after a certain time following carcinogen exposure inhibits tumor development. The paradoxical effects of the two oxidants depend on experimental design; results can be tentatively explained in terms of oxidant induced cell proliferation or by oxidant-mediated cytotoxicity. Besides being capable of modifying chemically induced lung tumorigenesis, ozone and oxygen also appear to induce tumors in mouse lung on their own. The conclusions drawn from the study of mouse lung tumors have recently been reinforced in experiments with hamsters, where hyperoxia has clear tumor-modulating effects.
[Witschi H; Exp Lung Res 17 (2): 473-83 (1991)]**PEER REVIEWED**

The effects of ozone on tracheal electrical potential were investigated in inbred strains of mice that are differentially susceptible to ozone induced inflammation. In male mice (9-13 wk), a tracheostomy was made under pentobarbital anesthesia for spontaneous breathing and tracheal potential was measured in the cephalad portion of the bisected trachea. The mean tracheal potentials of five different strains of mice (C3H/HeJ, DBA/2J, C57BL/6J, BALB/cJ, and 129/J) were 10 mV (lumen negative) with no significant interstrain difference. Amiloride reduced mouse tracheal potentials by 70% in both C3H/HeJ and C57BL/6J mice, indicating that sodium absorption is the predominant ion transport across this tissue. Relative to air-exposed controls, acute ozone exposure (2 ppm for 3 hr) significantly attenuated tracheal potential of inflammation-susceptible C57BL/6J mice by 50% at 6 hr and 40% at 24 hr postexposure but had no effect immediately after exposure. The mean tracheal potential of C3H/HeJ mice was not changed by ozone. The differential effect of acute ozone exposure on tracheal potential in C57BL/6J and C3H/HeJ mice is consistent with differential susceptibility to ozone induced increases in epithelial permeability in these strains.
[Takahashi M et al; Am J Physiol 265 (1 PART 1): L33-37 (1993)]**PEER REVIEWED**

OZONE CAUSES DESQUAMATION OF THE EPITHELIUM THROUGHOUT THE CILIATED AIRWAYS & PRODUCES DEGENERATIVE CHANGES IN TYPE-I CELLS & SWELLING OR RUPTURE OF THE CAPILLARY ENDOTHELIUM IN THE ALVEOLI. THE TYPE-I CELLS ARE LATER REPLACED BY TYPE-II CELLS.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1617]**PEER REVIEWED**

... CONCLUSIONS: Under the conditions of these 2 yr and lifetime inhalation studies, there was no evidence of carcinogenic activity of ozone in male or female F344/N rats exposed to 0.12, 0.5, or 1.0 ppm. There was equivocal evidence of carcinogenic activity of ozone in male B6C3F1 mice based on increased incidences of alveolar/bronchiolar adenoma or carcinoma. There was some evidence of carcinogenic activity of ozone in female B6C3F1 mice based on increased incidences of alveolar/bronchiolar adenoma or carcinoma. ...
[Toxicology & Carcinogenesis Studies of Ozone and Ozone/NNK in F344/N Rats and B6C3F1 Mice (Inhalation Studies). Technical Report Series No. 440 (1994) NTIS Publication No. 95-226999 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709]**QC REVIEWED**

National Toxicology Program Studies:

... Male and female F344/N rats and B6C3FI mice were exposed to ozone by inhalation for 4 weeks, 2 years, or for 124 weeks (rats) or 130 weeks (mice). The oxygen used to generate the ozone was greater than 99.9% pure. Additional groups of male F344/N rats were administered injections of 4-(N-methyl-Nnitrosamino)-1 -(3-pyridyl)-1-butanone (NNK) (~99% pure) ... for 2 years. ... 2 YEAR OZONE STUDY IN RATS: ... Groups of 50 male and 50 female F344/N rats were exposed to 0, 0.12, 0.5, or 1.0 ppm ozone by inhalation for 6 hours per day, 5 days/wk, for 105 wk. LIFETIME OZONE STUDY IN RATS: For this study, rats were exposed to 0.5 and 1.0 ppm ozone for an additional 6 mo to determine the effect of extended exposure on neoplasm incidence. Groups of 50 male and 50 female F344/N rats were exposed to 0, 0.5, or 1.0 ppm ozone by inhalation for 6 hr/day, 5 days/wk, for 125 wk. 2 YEAR OZONE STUDY IN MICE: ... Groups of 50 male and 50 female B6C3F1 mice were exposed to 0, 0.12, 0.5, or 1.0 ppm ozone by inhalation for 6 hr/day, 5 days/wk, for 105 wk. LIFETIME OZONE STUDY IN MICE: ... Groups of 50 male and 50 female B6C3F1 mice were exposed to 0, 0.5, or 1.0 ppm ozone by inhalation for 6 hr/day, 5 days/wk, for 130 wk. CONCLUSIONS: Under the conditions of these 2 yr and lifetime inhalation studies, there was no evidence of carcinogenic activity of ozone in male or female F344/N rats exposed to 0.12, 0.5, or 1.0 ppm. There was equivocal evidence of carcinogenic activity of ozone in male B6C3F1 mice based on increased incidences of alveolar/bronchiolar adenoma or carcinoma. There was some evidence of carcinogenic activity of ozone in female B6C3F1 mice based on increased incidences of alveolar/bronchiolar adenoma or carcinoma. ...
[Toxicology & Carcinogenesis Studies of Ozone and Ozone/NNK in F344/N Rats and B6C3F1 Mice (Inhalation Studies). Technical Report Series No. 440 (1994) NTIS Publication No. 95-226999 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709]**QC REVIEWED**

Metabolism/Pharmacokinetics:

Metabolism/Metabolites:

THE /SRP: REACTION/ ... OF OZONE IS MAINLY THROUGH THE OXIDATION OF LUNG LIPIDS. /SRP: OXIDATION/ REACTION PRODUCTS THAT MAY BE EXCRETED INCL MALONALDEHYDE, ETHANE, & PENTANE.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 4071]**PEER REVIEWED**

Absorption, Distribution & Excretion:

EXPT IN BEAGLE DOGS, RABBITS, & GUINEA PIGS INDICATE THAT MORE THAN HALF THE OZONE INHALED IS TAKEN UP BY THE NASAL & PHARYNGEAL MUCOSA, WITH EXPOSURES TO LESS THAN 2 PPM.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 4070]**PEER REVIEWED**

... IN MONKEYS, OZONE APPEARS TO BE ABSORBED ALONG THE ENTIRE RESPIRATORY TRACT,PENETRATING DEEPLY INTO THE PERIPHERAL, NONCILIATED AIRWAYS, & CAUSING ITS MOST CONSPICUOUS LESIONS IN THE RESPIRATORY BRONCHIOLES & ALVEOLAR DUCTS.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 4071]**PEER REVIEWED**

Ozone deposition velocity and ozone permeance were determined for a variety of isolated plant cuticles from the adaxial leaf surfaces. Ozone deposition velocity was lower than determined with whole plants kept in darkness. It declined continuously during exposure to the gas and showed a recovery effect after an interruption of the fumigation. It incr with the moisture content of the cuticles and decr when the ozone concn in the surrounding air was raised. The deposition velocity was much higher than cuticular ozone permeance at equiv ozone concn. Due to the ozone decay in the cuticle, ozone permeance was much lower in thick than in thincuticles. Even with the most permeable cuticles, ozone uptake under natural conditions is smaller than the flux through open stomata by a factor of at least 10,000.
[Kerstiens G, Lendzian KJ; New Phytol 112 (1): 13-9 (1989)]**PEER REVIEWED**

Transpiration and ozone uptake rates were measured simultaneously in sunflower (Helianthus annuus leguminosae) leaves at different stomatal openings and various ozone concn (0, 500, 1000 and 1500 nl/l). Ozone uptake rates were proportional to the ozone concn up to 1500 nl/l. During a light-induced incr in transpiration and in carbon dioxide uptake rates, the ozone uptake rate also increased. The leaf gas phase diffusion resistance (stomatal plus boundary layer) to water vapor was calculated and converted to the resistance to ozone multiplying it by the theoretical ratio of diffusion coefficients for water vapor and ozone in air (1.67). The ozone concn in intercellular air spaces calculated from the ozone uptake rate and diffusion resistance to ozone scattered around zero (0.43 to -7.55 umol/cu m). The ozone concn in intercellular air spaces was measured directly by supplying ozone to the leaf from one side and measuring the equilibrium concn above the other side and it was found to be zero. Total leaf resistance to ozone was proportional to the gas phase resistance to water vapor with a coefficient of 1.68.
[Laisk A et al; Plant Physiol 90 (3): 1163-7 (1989)]**PEER REVIEWED**

Transfer of ozone (O3) to forests is restricted by surface and internal resistances of foliage. O3 is efficiently absorbed through stomata. A multi-layer canopy gas and radiation exchange model (Maestro) was modified to calculate air pollutant deposition. Leaf boundary layer resistances, and stomatal resistances in the model were adjusted for gas molecular diffusivity, and leaf surface resistances and internal resistances were added. By using the proper resistances, Maestro may be used to model the deposition of O3.
[Unsworth MH, Wilshaw JC; Agric Forest Meteorol 47 (2-4): 221-38 (1989)]**PEER REVIEWED**

Biological Half-Life:

Oxygen 18 was used as a tracer for inhaled ozone in mice. The amount of ozone derived oxygen in the lung was determined by measuring the amount of oxygen 18 in excess of the natural abundance level which remained covalently bound to organic constituents of lung following exposure to 1 ppm ozone for up to 60 min. The rate of disappearance of ozone derived oxygen from the lung was determined by quantifying the rate of decrease of oxygen 18 in excess of the natural abundance level in lung from mice exposed to 1 ppm ozone 18 for 45 min. With exposure at 1 ppm ozone, ozone derived oxygen accumulated in lung at a rate of 4.38 pmol/mg dry weight/min. Ozone derived oxygen had a half-life in lung of about 6 hr. At least 44 pmol of ozone reacted with lung tissue every minute of exposure to 1 ppm ozone.
[Santrock J et al; Toxicol Appl Pharmacol 98 (1): 75-80 (1989)]**PEER REVIEWED**

Mechanism of Action:

THE BIOCHEMICAL MECHANISM OF PULMONARY INJURY PRODUCED BY OZONE MAY BE DUE TO THE FORMATION OF REACTIVE FREE-RADICAL INTERMEDIATES. OZONE-INDUCED FREE RADICALS MAY BE DERIVED FROM INTERACTION WITH SULFHYDRYL GROUPS, FROM OXIDATIVE DECOMP OF UNSATURATED FATTY ACIDS, OR BOTH. SEVERAL LINES OF EVIDENCE INDICATE THAT ONE OF THE BIOLOGICAL ACTIONS OF OZONE IS REACTION WITH UNSATURATED FATTY ACIDS. THE OZONIZATION OF THESE FATTY ACIDS IS ESSENTIALLY EQUIVALENT TO LIPID PEROXIDATION.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1617]**PEER REVIEWED**

OZONE CAUSES DESQUAMATION OF THE EPITHELIUM THROUGHOUT THE CILIATED AIRWAYS & PRODUCES DEGENERATIVE CHANGES IN TYPE-I CELLS & SWELLING OR RUPTURE OF THE CAPILLARY ENDOTHELIUM IN THE ALVEOLI. THE TYPE-I CELLS ARE LATER REPLACED BY TYPE-II CELLS.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1617]**PEER REVIEWED**

EFFECTS OF AMBIENT LEVELS OF OZONE ON CELL SIZE & COMPARTMENTS WERE DETERMINED MORPHOMETRICALLY FOR IN SITU & LAVAGED PULMONARY ALVEOLAR MACROPHAGES FROM RATS EXPOSED TO FILTERED AIR OR TO FILTERED AIR WITH 0.60 PPM OZONE. THE OZONE EXPOSURE WAS 8 HR/DAY FOR 3 DAYS. SIGNIFICANT EXPOSURE-RELATED COMPARTMENTAL VOLUME & DIAMETER CHANGES OF IN SITU CENTRIACINAR MACROPHAGES WERE: DECREASED ENDOPLASM; INCREASED LYSOSOME-LIKE STRUCTURES; DECREASED PRIMARY LYSOSOMES; INCREASED SMALL & LARGE SECONDARY LYSOSOMES; & DECREASED PHAGOSOMES/AUTOPHAGOSOMES.
[LUM H ET AL; EXP LUNG RES 5 (1): 61 (1983)]**PEER REVIEWED**

RABBITS WERE EXPOSED TO 0.4 PPM OZONE, 7 HR/DAY, 5 DAYS/WK FOR 6 WK, 2 WK AFTER PNEUMONECTOMY. EXPOSURE OF CONTROL ANIMALS TO OZONE RESULTED IN A 15% INCREASE IN LUNG VOLUME. LUNG GROWTH ACCOMPANYING PNEUMONECTOMY WAS NOT COMPROMISED UNDER CONDITIONS OF EXPOSURE TO OZONE, & MALES & FEMALES OF THE SAME AGE & BODY WEIGHT GAVE SIMILAR RESPONSES AS MEASURED BY MORPHOMETRIC PARAMETERS.
[BOATMAN ES ET AL; J APPL PHYSIOL RESPIR ENVIRON EXERCISE PHYSIOL 54 (3): 778 (1983)]**PEER REVIEWED**

Interactions:

THYROXINE WORSENED RESPONSE TO OZONE & ANIMALS DIED FROM OTHERWISE TOLERATED DOSES. ANTITHYROID DRUGS INCR RESISTANCE TO OZONE. NERVE-BLOCKING AGENTS (PHENOXYBENZAMINE OR ERGOTAMINE) IN THE ADRENALECTOMIZED RAT ALSO INCR RESISTANCE TO OZONE.
[Casarett, L.J., and J. Doull. Toxicology: The Basic Science of Poisons. New York: MacMillan Publishing Co., 1975. 545]**PEER REVIEWED**

INCR RESPIRATORY RESPONSE TO HISTAMINE INJECTED SC IN GUINEA PIGS TWO HR AFTER TWO-HR EXPOSURE TO 1 TO 5 PPM OZONE. INCR MORTALITY FROM HIGHER LEVELS OF HISTAMINE COULD BE PRODUCED BY AS LITTLE AS 0.5 TO 1 PPM OZONE. THE INCR SUSCEPTIBILITY PERSISTED UP TO 12 HR AFTER A TWO HR EXPOSURE TO 5 PPM OZONE.
[Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980. 620]**PEER REVIEWED**

ACUTE TOXICITY OF OZONE MAY BE LESSENED BY SIMULTANEOUS OR PRIOR INHALATION OR INJECTION OF ... SULFUR-CONTAINING COMPD. TECHNICAL-GRADE HYDROGEN SULFIDE GIVEN SIMULTANEOUSLY IN MOLAR RATIO OF 2:1 REDUCED MORTALITY PRODUCED BY WHAT WOULD HAVE BEEN LC50 CONCN OF OZONE TO 20%. ... MAJOR PROTECTION WAS OBTAINED BY IP INJECTION OF DIMETHYL DISULFIDE OR HYDROGEN POLYSULFIDE (ABOUT 20 MG/KG) PRIOR TO OZONE EXPOSURE.
[Casarett, L.J., and J. Doull. Toxicology: The Basic Science of Poisons. New York: MacMillan Publishing Co., 1975. 543]**PEER REVIEWED**

ELEVEN HEALTHY MALE SUBJECTS AGED 23 TO 38 YR WERE EXPOSED TO PURIFIED AIR, TO NO2, O3, & SO2 ALONE, TO MIXT OF NO2 + SO2, & NO2 + O3 IN MAX ALLOWABLE CONCN, & TO A MIXT OF NO2 + SO2 + O3 IN MAX ALLOWABLE CONCN. RESPIRATORY GAS EXCHANGE FOR O2 DECR & AIRWAY RESISTANCE INCR WAS OBSERVED IN ALL SERIES WITH NO2 IN MAX ALLOWABLE CONCN. THE COMBINATIONS OF NO2 + O3, NO2 + SO2, OR NO2 + SO2 + O3 DID NOT SHOW A STRONGER EFFECT THAN NO2 ALONE.
[VON NIEDING G ET AL; INT ARCH OCCUP ENVIRON HEALTH 43 (3): 195 (1979)]**PEER REVIEWED**

A STUDY IN RATS ACUTELY EXPOSED TO O3 (0.5-2.0 PPM) OR NO2 (2-20 PPM) FOR 2 HR & SACRIFICED IMMEDIATELY THEREAFTER SHOWS LITTLE SIMILARITY IN THE INDIVIDUAL BIOCHEMICAL EFFECTS OF THESE POLLUTANTS. OF INTEREST WAS THE FINDING THAT INHALATION OF NO2 INCR EXTENT TO WHICH CONCANAVALIN AGGLUTINATED ALVEOLAR MACROPHAGES WHILE O3 HAD EXACTLY OPPOSITE EFFECT.
[GOLDSTEIN BD; ENVIRON HEALTH PERSPECT 30: 87 (1979)]**PEER REVIEWED**

OZONE ... INCR THE SENSITIVITY OF THE LUNG TO BRONCHOCONSTRICTORS SUCH AS ... ACETYLCHOLINE, & ALLERGENS.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1617]**PEER REVIEWED**

THE EFFECT OF OZONE ON PENTOBARBITAL-INDUCED SLEEPING TIME WAS NOT SPECIFIC TO STRAIN OR SPECIES OF ANIMAL, BUT IT WAS SEX-SPECIFIC WITH FEMALES BEING MORE SENSITIVE. ALTHOUGH THE MECHANISM(S) FOR THE EFFECT OF OZONE ON PENTOBARBITAL-INDUCED SLEEPING TIME ARE NOT KNOWN DEFINITIVELY, APPARENTLY SOME COMMON ASPECT(S) OF DRUG METABOLISM IS QUANTITATIVELY REDUCED.
[GRAHAM JA ET AL; ADV MOD ENVIRON TOXICOL 5: 95 (1983)]**PEER REVIEWED**

YOUNG HEALTHY ADULT VOLUNTEERS RECEIVING 800 OR 1600 IU VITAMIN E PER DAY FOR 9 OR MORE WEEKS WERE EXPOSED FOR 2 HR PERIODS TO 0.5 PPM OZONE. RESPONSES TO OZONE EXPOSURES, EVALUATED IN TERMS OF SYMPTOMS, FORCED EXPIRATORY PERFORMANCE, & SINGLE-BREATH NITROGEN WASHOUT, WERE NOT SIGNIFICANTLY DIFFERENT BETWEEN VITAMIN E & PLACEBO GROUPS.
[HACKNEY JD ET AL; J TOXICOL ENVIRON HEALTH 7 (3-4): 383 (1981)]**PEER REVIEWED**

Specific pathogen-free CD-1 female mice were treated with 2.5 mg/kg of an interferon inducer or with an anti-interferon antibody (17,000 units activity/kg) one day prior to and during exposure to 0.7 or 0.9 ppm ozone. Exposure was for 20 hr/day for 4 days and controls were exposed to clean air or ozone after injection with balanced salt solution or control serum. All groups consisted of S-9 mice that were sacrificed after 5 days for removal and microscopic examination of the lung. Control injected mice exposed to ozone showed cell damage, reactive repair, and an influx of inflammatory cells in the centroacinar portion of the lung. Pretreatment with the interferon inducer reduced the lesion and anti-interferon increased the lesion when compared to controls exposed to ozone. At both levels of ozone exposure, interferon-induced, ozone-exposed mice had less alveolar damage; however, anti-interferon treated, ozone-exposed mice had larger alveolar lesions extensively infiltrated by neutrophilic leukocytes when compared to control injected, ozone exposed mice.
[Dziedzic D, White HJ; Toxicol Lett 39 (1): 51-62 (1987)]**PEER REVIEWED**

Male ICR mice, golden hamsters, Wistar rats, and Hartley guinea pigs (6 animals/group) were exposed to a mixture of 0.4 ppm nitrogen dioxide and 0.4 ppm ozone for 2 wk. Controls were exposed to clean air in a similar exposure chamber. It was shown that the concentrations of lipid peroxides (using as an index the concentrations of thiobarbituric acid reactants) in lung tissue of guinea pigs and mice, exposed to the combined gases, were increased significantly when compared to the controls, (for guinea pigs: p< 0.01 at 7 days, p< 0.001 at 14 days; for mice: p< 0.05 at 7 days, p< 0.001 at 14 days). However, the lipid peroxide levels of hamsters and rats did not show any significant changes throughout the 2 wk of exposure. Significant increases in total phospholipids were observed in mice, rats, and guinea pigs, but not in hamsters.
[Sagai M et al; Toxicology 46: 251-65 (1987)]**PEER REVIEWED**

Primary hamster cells and C3H/10T-1/2 cells were put in saline and exposed to 6 ppm ozone (O3) for 10 min. Saline was then removed and replaced with complete medium. Exposures to UV light were carried out by exposing hamster and mouse C3H/10T-1/2 primary cultures to UV light at 254 nm at a dose rate of 4 J/sq m. Combined exposures to UV and ozone were carried out by irradiating the cells with UV light (4 J/sq m) 10 min prior to treating them with 6 ppm of ozone for 10 min. Treatment of hamster embryo and mouse C3H/10T-1/2 cells with O3 resulted in enhanced cell transformation compared to control untreated cells. Ozone acted in additive fashion with ultraviolet light to produce enhanced levels of transformation in both hamster and mouse cells. The transformation frequencies of hamster embryo cells were 0% for controls, 2.6% for O3 treated, 7.7% for UV treated and 13.2% for O3 + UV treated cells. For mouse cells, the transformation frequencies were 0%, 1.6%, 5.3% and 8.9%, respectively.
[Borek C et al; Teratogenesis Carcinogen Mutagen 9 (2): 71-4 (1989)]**PEER REVIEWED**

Male Jcl: Wistar rats (n= 12 per group) were exposed continuously to filtered air (controls), 0.2 ppm ozone (O3), 4 ppm nitrogen dioxide (NO2), or 4 ppm NO2 and 0.2 ppm O3, continuously for 1 and 2 mo to examine the effects of combined gas on the xenobiotic metabolizing systems of lung microsomes. The cytochrome p450 content increased to 200% and 253% (both p < 0.001) of the control values during 2 mo exposures to O3 while it was not increased by NO2 exposures. Addition of NO2 to O3 reduced the increased level of cytochrome p450 to 179% and 178% (both p < 0.001) of the control values. The activities of cytochrome p450 dependent monooxygenase, benzo(a)pyrene hydroxylase and 7-ethoxycoumarin O-deethylase were changed in the same fashion by exposures to NO2 and O3. The 7-ethoxycoumarin O-deethylase activity was increased to 147% and 142% (both p < 0.001) of the control values by 03 exposure, whereas it was decr to 71% and 75% (both p < 0.01) of the control values by NO2 exposures. This activity was decr to 124% (p < 0.05) and 97% of the control values by combination of O3 with NO2 after 1 and 2 mo, respectively. Similarly, the benzo(a)pyrene hydroxylase activity was increased to 157% and 153% (both p < 0.001) of the control values during O3 exposures, while it was not changed by NO2 exposures. Addition of NO2 to O3 reduced the activity to 140% (p < 0.01) and 115% of the control values after 1 and 2 mo, respectively. The alteration of coumarin hydroxylase activity was different from those of others. This activity decr to 44% and 29% (both p < 0.001) of the control values after 1 and 2 mo exposures to NO2, respectively, and was decr to 19% of controls after 0.2 ppm O3 exposure (p < 0.05). However, the magnitude of decr was not reinforced by combination of NO2 with O3.
[Takahashi Y, Miura T; Toxicology 56 (3): 253-62 (1989)]**PEER REVIEWED**

Mouse C3H10T1/2 cells were exposed to 5 or 1 ppm ozone (O3) for 5 min. Some of the cell cultures were exposed to gamma rays (4 or 0.4 Gy) immediately before or after O3 treatment. Following 6 wk in culture, transformation was scored using morphological criteria. O3 (at 5 ppm) and radiation act as independent carcinogens /SRP: transformation co-inducing agent/ when cells are exposed to O3 prior to radiation. When cells are first exposed to radiation, transformation is markedly enhanced in a synergistic manner. The transformation frequency of 5 ppm O3 after 4 Gy irradiation was 16.6X10+4 vs a frequency of 7.2X10+4 predicted based on independent action. O3 at 1 ppm does not induce transformation, but acts as a co-carcinogen. High molecular wt DNAs extracted from the 3 independently O3 transformed cell lines induced the appearance of transformed colonies in mouse C3H10T/2 cells. DNAs from untreated or O3 treated untransformed cells did not induce the appearance of transformed colonies.
[Borek C et al; Carcinogenesis 10 (8): 1549-51 (1989)]**PEER REVIEWED**

WHEN INHALED AT CONCN NOT ACUTELY INJURIOUS PER SE MAY INITIATE, ACCELERATE OR EXACERBATE RESPIRATORY TRACT DISEASE OF BACTERIAL OR VIRAL ORIGIN.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values, 4th ed., 1980. Cincinnati, Ohio: American Conference of Governmmental Industrial Hygienists, Inc., 1980.316]**PEER REVIEWED**

Nitric acid is themost prevalent acid air pollutant in the western United States and has the potential to cause adverse respiratory effects through both acidification and oxidation reactions. A study measured physiologic (specific airway resistance, SRaw, FEV1, and FVC) and bronchoalveolar lavage (total and differential cell counts, LDH, fibronectin, and total protein) end points in a group of 10 healthy, athletic subjects who were exposed to 500 ug/cu m of nitric acid gas or filtered air for 4 hr during moderate exercise (ventilatory rate, 40 l/min) and underwent bronchoscopy 18 hr later. Under an identical protocol, 10 healthy subjects were exposed to 500 ug/cu m of nitric acid gas plus 0.20 ppm ozone or 0.20 ppm ozone alone to determine if nitric acid might enhance the toxicity of ozone. In addition to bronchoalveolar lavage, the techniques of isolated left mainstem bronchial lavage and bronchial biopsy were used to determine if proximal airway injury was caused by pollutant exposure and whether there was any correlation with the degree of distal lung injury as assessed by bronchoalveolar lavage. No significant differences were found in pulmonary function tests or in the cellular or biochemical constituents in either the bronchoalveolar lavage or the left mainstem lavage fluids between the nitric acid and the air exposures. Similarly, there were no differences in these end points between the nitric acid/ozone and the ozone exposures. Furthermore, there were no significant differences in the bronchial biopsy specimens between the nitric acid and air exposures or between the nitric acid/ozone and ozone exposures.
[Aris R et al; Am Rev Respir Dis 148 (4 Pt 1): 965-73 (1993)]**PEER REVIEWED**

Airway hyperresponsiveness is a key feature of asthma, and attenuating airway hyperresponsiveness is an important part of asthma therapy. The /study/ examined the inhibitory effect of a potent 5-lipoxygenase inhibitor, FR110302, on airway hyperresponsiveness induced by ozone exposure in guinea pigs and dogs. Respiratory resistance was measured by a forced oscillation method. Airway responsiveness was determined from the dose-response curve of respiratory resistance to acetylcholine. Guinea pigs were exposed to 2.5 ppm ozone for 1 hr. In a control group of guinea pigs, delta log PC100 (the index of the ozone induced airway hyperresponsiveness) was 0.58 + or - 0.04 (log mg/ml). Treatment with FR110302 (10 or 100 mg/kg p.o.) significantly diminished delta log PC100 (10 mg/kg: 0.22 + or - 0.10; 100 mg/kg; 0.11 + or - 0.06). Dogs were exposed to 3 ppm ozone for 2 hr. In a control group of dogs, delta log Dmin (another index of the ozone induced airway hyperresponsiveness) was 1.24 + or - 0.15 (log unit). Treatment with FR110302 (1 or 3.2 mg/kg orally) significantly diminished delta log Dmin (1 mg/kg: 0.60 + or - 0.18; 3.2 mg/kg: 0.27 + or - 0.12).
[Asano M et al; Agents Actions 38 (3-4): 171-7 (1993)]**PEER REVIEWED**

Sprague-Dawley rats were exposed for 6 hr daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis.
[Last JA et al; Am Rev Respir Dis 148 (2): 487-94 (1993)]**PEER REVIEWED**

Ozone exposure results in an acute decrease in the serum levels of thyroid hormones. Physiologic sequelae of this are unclear. Whereas thyroid hormone supplementation appears to benefit pulmonary function in septic, oxyradical models of injury, thyroid hormone increases ozone toxicity. An increase in metabolic rate and pulmonary injury was demonstrated in lungs from ozone exposed, triiodothyronine treated animals. This was evidenced by an increase in pulmonary weight gain, vascular perfusion pressure, and decrease in compliance in the supplemented animals. However, an increase in alkane generation, as an index of lipid peroxidation, was not seen in the ozone exposed, hormonally treated animals. Although thyroid hormone supplementation increases metabolic rate and ozone toxicity, an increased rate of lipid peroxidation plays a minimal role.
[Sen S et al; Free Radic Res Commun 18 (5): 299-308 (1993)]**PEER REVIEWED**

In a study of in vitro transformation, ozone (6 ppm for 10 min) acts in additive fashion with ultraviolet light (4 J/sq m) to produce enhanced levels of transformation in hamster embryo cells and mouse C3H/10T-1/2 cells as compared to rats induced by each of the agents alone.
[Borek C et al; Teratogenesis Carcinog Mutagen 9 (2): 71-4 (1989)]**PEER REVIEWED**

Seedlings of Jeffrey pine (Pinus jeffreyi) and giant sequoia (Sequoiadendron gigantea) were more susceptible to leaf chemical changes following exposure in greenhouses to acid mist (pH 3.4 to 2.0) or acid mist/ozone combinations, than to ozone alone (0.1 to 0.2 ul/l), when plants were exposed to alternating doses of these pollutants. Experimental studies were conducted for 6 weeks starting 23 May 1985 and for 9 weeks starting 2 May 1986. Ozone treatment produced no effects in either species except for a rise in potassium and magnessium in new leaves of Jeffrey pine in the 1986 experiment. In field studies, limited foliage samples collected from these two species in 1985 and 1986 in Sequoia/Kings Canyon National Parks did not indicate any clearcut or severe effects of ozone alone on leaf chemistry.
[Westman WE, Temple PJ; Environ Pollut 57 (1): 9-26 (1989)]**PEER REVIEWED**

Pharmacology:

Interactions:

THYROXINE WORSENED RESPONSE TO OZONE & ANIMALS DIED FROM OTHERWISE TOLERATED DOSES. ANTITHYROID DRUGS INCR RESISTANCE TO OZONE. NERVE-BLOCKING AGENTS (PHENOXYBENZAMINE OR ERGOTAMINE) IN THE ADRENALECTOMIZED RAT ALSO INCR RESISTANCE TO OZONE.
[Casarett, L.J., and J. Doull. Toxicology: The Basic Science of Poisons. New York: MacMillan Publishing Co., 1975. 545]**PEER REVIEWED**

INCR RESPIRATORY RESPONSE TO HISTAMINE INJECTED SC IN GUINEA PIGS TWO HR AFTER TWO-HR EXPOSURE TO 1 TO 5 PPM OZONE. INCR MORTALITY FROM HIGHER LEVELS OF HISTAMINE COULD BE PRODUCED BY AS LITTLE AS 0.5 TO 1 PPM OZONE. THE INCR SUSCEPTIBILITY PERSISTED UP TO 12 HR AFTER A TWO HR EXPOSURE TO 5 PPM OZONE.
[Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980. 620]**PEER REVIEWED**

ACUTE TOXICITY OF OZONE MAY BE LESSENED BY SIMULTANEOUS OR PRIOR INHALATION OR INJECTION OF ... SULFUR-CONTAINING COMPD. TECHNICAL-GRADE HYDROGEN SULFIDE GIVEN SIMULTANEOUSLY IN MOLAR RATIO OF 2:1 REDUCED MORTALITY PRODUCED BY WHAT WOULD HAVE BEEN LC50 CONCN OF OZONE TO 20%. ... MAJOR PROTECTION WAS OBTAINED BY IP INJECTION OF DIMETHYL DISULFIDE OR HYDROGEN POLYSULFIDE (ABOUT 20 MG/KG) PRIOR TO OZONE EXPOSURE.
[Casarett, L.J., and J. Doull. Toxicology: The Basic Science of Poisons. New York: MacMillan Publishing Co., 1975. 543]**PEER REVIEWED**

ELEVEN HEALTHY MALE SUBJECTS AGED 23 TO 38 YR WERE EXPOSED TO PURIFIED AIR, TO NO2, O3, & SO2 ALONE, TO MIXT OF NO2 + SO2, & NO2 + O3 IN MAX ALLOWABLE CONCN, & TO A MIXT OF NO2 + SO2 + O3 IN MAX ALLOWABLE CONCN. RESPIRATORY GAS EXCHANGE FOR O2 DECR & AIRWAY RESISTANCE INCR WAS OBSERVED IN ALL SERIES WITH NO2 IN MAX ALLOWABLE CONCN. THE COMBINATIONS OF NO2 + O3, NO2 + SO2, OR NO2 + SO2 + O3 DID NOT SHOW A STRONGER EFFECT THAN NO2 ALONE.
[VON NIEDING G ET AL; INT ARCH OCCUP ENVIRON HEALTH 43 (3): 195 (1979)]**PEER REVIEWED**

A STUDY IN RATS ACUTELY EXPOSED TO O3 (0.5-2.0 PPM) OR NO2 (2-20 PPM) FOR 2 HR & SACRIFICED IMMEDIATELY THEREAFTER SHOWS LITTLE SIMILARITY IN THE INDIVIDUAL BIOCHEMICAL EFFECTS OF THESE POLLUTANTS. OF INTEREST WAS THE FINDING THAT INHALATION OF NO2 INCR EXTENT TO WHICH CONCANAVALIN AGGLUTINATED ALVEOLAR MACROPHAGES WHILE O3 HAD EXACTLY OPPOSITE EFFECT.
[GOLDSTEIN BD; ENVIRON HEALTH PERSPECT 30: 87 (1979)]**PEER REVIEWED**

OZONE ... INCR THE SENSITIVITY OF THE LUNG TO BRONCHOCONSTRICTORS SUCH AS ... ACETYLCHOLINE, & ALLERGENS.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1617]**PEER REVIEWED**

THE EFFECT OF OZONE ON PENTOBARBITAL-INDUCED SLEEPING TIME WAS NOT SPECIFIC TO STRAIN OR SPECIES OF ANIMAL, BUT IT WAS SEX-SPECIFIC WITH FEMALES BEING MORE SENSITIVE. ALTHOUGH THE MECHANISM(S) FOR THE EFFECT OF OZONE ON PENTOBARBITAL-INDUCED SLEEPING TIME ARE NOT KNOWN DEFINITIVELY, APPARENTLY SOME COMMON ASPECT(S) OF DRUG METABOLISM IS QUANTITATIVELY REDUCED.
[GRAHAM JA ET AL; ADV MOD ENVIRON TOXICOL 5: 95 (1983)]**PEER REVIEWED**

YOUNG HEALTHY ADULT VOLUNTEERS RECEIVING 800 OR 1600 IU VITAMIN E PER DAY FOR 9 OR MORE WEEKS WERE EXPOSED FOR 2 HR PERIODS TO 0.5 PPM OZONE. RESPONSES TO OZONE EXPOSURES, EVALUATED IN TERMS OF SYMPTOMS, FORCED EXPIRATORY PERFORMANCE, & SINGLE-BREATH NITROGEN WASHOUT, WERE NOT SIGNIFICANTLY DIFFERENT BETWEEN VITAMIN E & PLACEBO GROUPS.
[HACKNEY JD ET AL; J TOXICOL ENVIRON HEALTH 7 (3-4): 383 (1981)]**PEER REVIEWED**

Specific pathogen-free CD-1 female mice were treated with 2.5 mg/kg of an interferon inducer or with an anti-interferon antibody (17,000 units activity/kg) one day prior to and during exposure to 0.7 or 0.9 ppm ozone. Exposure was for 20 hr/day for 4 days and controls were exposed to clean air or ozone after injection with balanced salt solution or control serum. All groups consisted of S-9 mice that were sacrificed after 5 days for removal and microscopic examination of the lung. Control injected mice exposed to ozone showed cell damage, reactive repair, and an influx of inflammatory cells in the centroacinar portion of the lung. Pretreatment with the interferon inducer reduced the lesion and anti-interferon increased the lesion when compared to controls exposed to ozone. At both levels of ozone exposure, interferon-induced, ozone-exposed mice had less alveolar damage; however, anti-interferon treated, ozone-exposed mice had larger alveolar lesions extensively infiltrated by neutrophilic leukocytes when compared to control injected, ozone exposed mice.
[Dziedzic D, White HJ; Toxicol Lett 39 (1): 51-62 (1987)]**PEER REVIEWED**

Male ICR mice, golden hamsters, Wistar rats, and Hartley guinea pigs (6 animals/group) were exposed to a mixture of 0.4 ppm nitrogen dioxide and 0.4 ppm ozone for 2 wk. Controls were exposed to clean air in a similar exposure chamber. It was shown that the concentrations of lipid peroxides (using as an index the concentrations of thiobarbituric acid reactants) in lung tissue of guinea pigs and mice, exposed to the combined gases, were increased significantly when compared to the controls, (for guinea pigs: p< 0.01 at 7 days, p< 0.001 at 14 days; for mice: p< 0.05 at 7 days, p< 0.001 at 14 days). However, the lipid peroxide levels of hamsters and rats did not show any significant changes throughout the 2 wk of exposure. Significant increases in total phospholipids were observed in mice, rats, and guinea pigs, but not in hamsters.
[Sagai M et al; Toxicology 46: 251-65 (1987)]**PEER REVIEWED**

Primary hamster cells and C3H/10T-1/2 cells were put in saline and exposed to 6 ppm ozone (O3) for 10 min. Saline was then removed and replaced with complete medium. Exposures to UV light were carried out by exposing hamster and mouse C3H/10T-1/2 primary cultures to UV light at 254 nm at a dose rate of 4 J/sq m. Combined exposures to UV and ozone were carried out by irradiating the cells with UV light (4 J/sq m) 10 min prior to treating them with 6 ppm of ozone for 10 min. Treatment of hamster embryo and mouse C3H/10T-1/2 cells with O3 resulted in enhanced cell transformation compared to control untreated cells. Ozone acted in additive fashion with ultraviolet light to produce enhanced levels of transformation in both hamster and mouse cells. The transformation frequencies of hamster embryo cells were 0% for controls, 2.6% for O3 treated, 7.7% for UV treated and 13.2% for O3 + UV treated cells. For mouse cells, the transformation frequencies were 0%, 1.6%, 5.3% and 8.9%, respectively.
[Borek C et al; Teratogenesis Carcinogen Mutagen 9 (2): 71-4 (1989)]**PEER REVIEWED**

Male Jcl: Wistar rats (n= 12 per group) were exposed continuously to filtered air (controls), 0.2 ppm ozone (O3), 4 ppm nitrogen dioxide (NO2), or 4 ppm NO2 and 0.2 ppm O3, continuously for 1 and 2 mo to examine the effects of combined gas on the xenobiotic metabolizing systems of lung microsomes. The cytochrome p450 content increased to 200% and 253% (both p < 0.001) of the control values during 2 mo exposures to O3 while it was not increased by NO2 exposures. Addition of NO2 to O3 reduced the increased level of cytochrome p450 to 179% and 178% (both p < 0.001) of the control values. The activities of cytochrome p450 dependent monooxygenase, benzo(a)pyrene hydroxylase and 7-ethoxycoumarin O-deethylase were changed in the same fashion by exposures to NO2 and O3. The 7-ethoxycoumarin O-deethylase activity was increased to 147% and 142% (both p < 0.001) of the control values by 03 exposure, whereas it was decr to 71% and 75% (both p < 0.01) of the control values by NO2 exposures. This activity was decr to 124% (p < 0.05) and 97% of the control values by combination of O3 with NO2 after 1 and 2 mo, respectively. Similarly, the benzo(a)pyrene hydroxylase activity was increased to 157% and 153% (both p < 0.001) of the control values during O3 exposures, while it was not changed by NO2 exposures. Addition of NO2 to O3 reduced the activity to 140% (p < 0.01) and 115% of the control values after 1 and 2 mo, respectively. The alteration of coumarin hydroxylase activity was different from those of others. This activity decr to 44% and 29% (both p < 0.001) of the control values after 1 and 2 mo exposures to NO2, respectively, and was decr to 19% of controls after 0.2 ppm O3 exposure (p < 0.05). However, the magnitude of decr was not reinforced by combination of NO2 with O3.
[Takahashi Y, Miura T; Toxicology 56 (3): 253-62 (1989)]**PEER REVIEWED**

Mouse C3H10T1/2 cells were exposed to 5 or 1 ppm ozone (O3) for 5 min. Some of the cell cultures were exposed to gamma rays (4 or 0.4 Gy) immediately before or after O3 treatment. Following 6 wk in culture, transformation was scored using morphological criteria. O3 (at 5 ppm) and radiation act as independent carcinogens /SRP: transformation co-inducing agent/ when cells are exposed to O3 prior to radiation. When cells are first exposed to radiation, transformation is markedly enhanced in a synergistic manner. The transformation frequency of 5 ppm O3 after 4 Gy irradiation was 16.6X10+4 vs a frequency of 7.2X10+4 predicted based on independent action. O3 at 1 ppm does not induce transformation, but acts as a co-carcinogen. High molecular wt DNAs extracted from the 3 independently O3 transformed cell lines induced the appearance of transformed colonies in mouse C3H10T/2 cells. DNAs from untreated or O3 treated untransformed cells did not induce the appearance of transformed colonies.
[Borek C et al; Carcinogenesis 10 (8): 1549-51 (1989)]**PEER REVIEWED**

WHEN INHALED AT CONCN NOT ACUTELY INJURIOUS PER SE MAY INITIATE, ACCELERATE OR EXACERBATE RESPIRATORY TRACT DISEASE OF BACTERIAL OR VIRAL ORIGIN.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values, 4th ed., 1980. Cincinnati, Ohio: American Conference of Governmmental Industrial Hygienists, Inc., 1980.316]**PEER REVIEWED**

Nitric acid is themost prevalent acid air pollutant in the western United States and has the potential to cause adverse respiratory effects through both acidification and oxidation reactions. A study measured physiologic (specific airway resistance, SRaw, FEV1, and FVC) and bronchoalveolar lavage (total and differential cell counts, LDH, fibronectin, and total protein) end points in a group of 10 healthy, athletic subjects who were exposed to 500 ug/cu m of nitric acid gas or filtered air for 4 hr during moderate exercise (ventilatory rate, 40 l/min) and underwent bronchoscopy 18 hr later. Under an identical protocol, 10 healthy subjects were exposed to 500 ug/cu m of nitric acid gas plus 0.20 ppm ozone or 0.20 ppm ozone alone to determine if nitric acid might enhance the toxicity of ozone. In addition to bronchoalveolar lavage, the techniques of isolated left mainstem bronchial lavage and bronchial biopsy were used to determine if proximal airway injury was caused by pollutant exposure and whether there was any correlation with the degree of distal lung injury as assessed by bronchoalveolar lavage. No significant differences were found in pulmonary function tests or in the cellular or biochemical constituents in either the bronchoalveolar lavage or the left mainstem lavage fluids between the nitric acid and the air exposures. Similarly, there were no differences in these end points between the nitric acid/ozone and the ozone exposures. Furthermore, there were no significant differences in the bronchial biopsy specimens between the nitric acid and air exposures or between the nitric acid/ozone and ozone exposures.
[Aris R et al; Am Rev Respir Dis 148 (4 Pt 1): 965-73 (1993)]**PEER REVIEWED**

Airway hyperresponsiveness is a key feature of asthma, and attenuating airway hyperresponsiveness is an important part of asthma therapy. The /study/ examined the inhibitory effect of a potent 5-lipoxygenase inhibitor, FR110302, on airway hyperresponsiveness induced by ozone exposure in guinea pigs and dogs. Respiratory resistance was measured by a forced oscillation method. Airway responsiveness was determined from the dose-response curve of respiratory resistance to acetylcholine. Guinea pigs were exposed to 2.5 ppm ozone for 1 hr. In a control group of guinea pigs, delta log PC100 (the index of the ozone induced airway hyperresponsiveness) was 0.58 + or - 0.04 (log mg/ml). Treatment with FR110302 (10 or 100 mg/kg p.o.) significantly diminished delta log PC100 (10 mg/kg: 0.22 + or - 0.10; 100 mg/kg; 0.11 + or - 0.06). Dogs were exposed to 3 ppm ozone for 2 hr. In a control group of dogs, delta log Dmin (another index of the ozone induced airway hyperresponsiveness) was 1.24 + or - 0.15 (log unit). Treatment with FR110302 (1 or 3.2 mg/kg orally) significantly diminished delta log Dmin (1 mg/kg: 0.60 + or - 0.18; 3.2 mg/kg: 0.27 + or - 0.12).
[Asano M et al; Agents Actions 38 (3-4): 171-7 (1993)]**PEER REVIEWED**

Sprague-Dawley rats were exposed for 6 hr daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis.
[Last JA et al; Am Rev Respir Dis 148 (2): 487-94 (1993)]**PEER REVIEWED**

Ozone exposure results in an acute decrease in the serum levels of thyroid hormones. Physiologic sequelae of this are unclear. Whereas thyroid hormone supplementation appears to benefit pulmonary function in septic, oxyradical models of injury, thyroid hormone increases ozone toxicity. An increase in metabolic rate and pulmonary injury was demonstrated in lungs from ozone exposed, triiodothyronine treated animals. This was evidenced by an increase in pulmonary weight gain, vascular perfusion pressure, and decrease in compliance in the supplemented animals. However, an increase in alkane generation, as an index of lipid peroxidation, was not seen in the ozone exposed, hormonally treated animals. Although thyroid hormone supplementation increases metabolic rate and ozone toxicity, an increased rate of lipid peroxidation plays a minimal role.
[Sen S et al; Free Radic Res Commun 18 (5): 299-308 (1993)]**PEER REVIEWED**

In a study of in vitro transformation, ozone (6 ppm for 10 min) acts in additive fashion with ultraviolet light (4 J/sq m) to produce enhanced levels of transformation in hamster embryo cells and mouse C3H/10T-1/2 cells as compared to rats induced by each of the agents alone.
[Borek C et al; Teratogenesis Carcinog Mutagen 9 (2): 71-4 (1989)]**PEER REVIEWED**

Seedlings of Jeffrey pine (Pinus jeffreyi) and giant sequoia (Sequoiadendron gigantea) were more susceptible to leaf chemical changes following exposure in greenhouses to acid mist (pH 3.4 to 2.0) or acid mist/ozone combinations, than to ozone alone (0.1 to 0.2 ul/l), when plants were exposed to alternating doses of these pollutants. Experimental studies were conducted for 6 weeks starting 23 May 1985 and for 9 weeks starting 2 May 1986. Ozone treatment produced no effects in either species except for a rise in potassium and magnessium in new leaves of Jeffrey pine in the 1986 experiment. In field studies, limited foliage samples collected from these two species in 1985 and 1986 in Sequoia/Kings Canyon National Parks did not indicate any clearcut or severe effects of ozone alone on leaf chemistry.
[Westman WE, Temple PJ; Environ Pollut 57 (1): 9-26 (1989)]**PEER REVIEWED**

Environmental Fate & Exposure:

Probable Routes of Human Exposure:

... FOUND ... AROUND SOURCES OF X-RAYS AND UV RAYS, ELECTRIC ARCS (WELDING AND SPECTROGRAPHIC EQUIPMENT, FOR EXAMPLE), MERCURY VAPOR LAMPS, ULTRA-BILLION-VOLT LINEAR ACCELERATORS AND ELECTRICAL DISCHARGES IN GENERAL.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 1579]**PEER REVIEWED**

Natural Pollution Sources:

FORMED LOCALLY IN AIR FROM LIGHTNING, IN STRATOSPHERE BY UV RADIATION
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 864]**PEER REVIEWED**

FOUND IN ATMOSPHERE IN VARYING PROPORTIONS (ABOUT 0.05 PPM @ SEA LEVEL), SINCE IT IS PRODUCED CONTINUOUSLY INTHE OUTER LAYERS OF THE ATMOSPHERE BY THE ACTION OF SOLAR UV RADIATION ON THE OXYGEN OF THE AIR.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1105]**PEER REVIEWED**

Artificial Pollution Sources:

ALSO OCCURS ... BY ELECTROLYSIS OF ALKALINE PERCHLORATE SOLN.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 864]**PEER REVIEWED**

REACTION BETWEEN ATOMIC OXYGEN & MOL OXYGEN RESULTS IN FORMATION OF OZONE, THE PRINCIPAL OXIDIZING AGENT OF PHOTOCHEMICAL SMOG. FURTHER REACTIONS INVOLVE OZONE & REACTIVE HYDROCARBONS (OLEFINS) TO PRODUCE MANY PRODUCTS, NATURE OF WHICH IS NOT YET FULLY KNOWN.
[Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969. 693]**PEER REVIEWED**

Ozone is ... is formed through complex chemical reactions between precursor emissions of volatile organic compounds like hydrocarbons and nitrogen oxides in the presence of sunlight.
[Sullivan TFP; Pollution Engineering p.24 (6/87)]**PEER REVIEWED**

Simultaneous, high resolution measurements of ozone (O3), NO, CO, dew point temp, and UV flux obtained during the NASA Global Tropospheric Experiment Chemical Instrumentation Test and Evaluation (GTE/CITE l) spring 1984 airborne field exercise over the eastern North Pacific Ocean were analyzed. The mid tropospheric O3 mixing ratio averaged about 48 + or - 15 parts per billion by volume (ppbv). Statistical analysis of the high resolution data indicates the existence of two O3 sources: one related to the downward transport of ozone- rich air from the upper troposphere and stratosphere and the other to the transport of O3-rich air from the continents.
[Chameides WL et al; J Geophys Res (D) Atmos 94 (7): 9799-808 (1989)]**PEER REVIEWED**

Environmental Fate:

A photochemical model was used to quantify the sensitivity of the tropospheric oxidants ozone (O3) and OH to changes in methane (CH4), carbon monoxide (CO), and NO emissions and to perturbations in climate and stratospheric chemistry. Coefficients of the form delta ln[O3]/delta ln[X] and delta ln[OH]/delta ln[X], where [X]= flux of CH4, CO, NO, stratospheric O3, and H2O have been calculated for a number of chemically coherent regions (e.g. nonpolluted continental, nonpolluted marine, urban) at low and middle latitudes. Sensitivities in O3 and OH vary with regional emissions patterns and are nonlinear within a given region as [X] changes. In most cases incr CH4 an CO emissions will suppress OH (neg coefficients) in incr O3 (pos coefficients) except in areas where NO and O3 influenced by pollution are sufficient to incr OH. Stratospheric O3 depletion will tend to decr O3 (except in high NOx areas) and incr OH through enhanced UV photolysis. Incr levels of water vapor (one possible outcome of a global warming) will also decr O3 and incr OH. In most regions, NO, CO and CH4 emission incr will suppress OH and incr O3, but these trends may be opposed by stratospheric O3 depletion and climate change. A regional survey of OH and O3 levels suggests that the tropics have a pivotal role in determining the earth's future oxidizing capacity.
[Thompson AM, Stewart RW; Atmos Environ 23 (3): 519-32 (1989)]**PEER REVIEWED**

Ozone concn above 80 ppb are common in the East U.S. in spring and summer, but they are unusual in the West, and ozone shows considerably more day-to-day variability in the East. Variations in ozone levels are highly correlated over distances of several hundred kilometers in the East, indicating that high values are associated with episodes of large spatial scale, > 600,000 sq km. There were 10 and 7 such episodes in 1978 and 1979, respectively, between the mo of Apr and Sept; they persisted for 3-4 days, on avg, with a range of 2-8 days, and were most common in Jun. Daily max ozone values exceeded 90 ppb at over half the sites during these episodes and were often > 120 ppb at one or more sites. An analysis of the meteorology for each episode shows that they occurred preferentially in the presence of weak, slow-moving, and persistent high-pressure systems. Two episodes that occurred outside the summer half of the yr were associated with unseasonably warm weather; only 1 episode, in Mar 1978, appeared to reflect a major stratospheric intrusion. Concn of NOx at rural locations in the East are frequently high enough (> 1 ppb) to permit significant photochemical formation of ozone. It is clear that rural ozone in the East in spring and summer is severely impacted by anthropogenic emissions of NOx and hydrocarbons, and that ozone episodes occur when the weather is particularly conducive to photochemical formation of ozone. Ozone episodes were present on 23% of days in May-Aug in the East in 1978-1979.
[Logan JA; J Geophys Res (D) 94 (6): 8511-32 (1989)]**PEER REVIEWED**

Measurements from the eastern north Pacific stratocumulus regime have been used to study components of the regional ozone budget. The surface destruction rate was determined by eddy correlation of ozone and vertical velocity measured during 8 flights of a low flying aircraft. Significant variability (2580 to 6460 s/m) was found in the measured surface resistance; it was partially correlated with friction velocity but appears to have other controlling influences as well. The mean resistance was 4190 + or - 840 s/m, which is higher (slower destruction) than most previous estimates for seawater. Flux and mean measurements throughout the marine boundary layer were used to estimate the net rate of in-situ photochemical production/destruction of ozone. Averaged over the flights, ozone concn was found to be near steady state, and a net photochemical destruction of 0.02 to 0.07 ng/cu m/sec was diagnosed. Ozone vertical distributions above the boundary layer showed a strongly layered structure with very sharp gradients.
[Kawa SR, Pearson R; J Geophys Res (D) Atmos 94 (7): 9809-17 (1989)]**PEER REVIEWED**

The results from a two dimensional model were analyzed to determine the principal modes of balance for ozone (O3) concn in different regions of the stratosphere. The analysis showed that except near the poles, O3 is in photochemical equilibrium above 35 km. In the lower stratosphere, equatorward of 50 degrees, concn of O3 is neither photochemically controlled nor transport controlled, but is set by a balance between transport and chemical processes. The low abundance of O3 in the tropics is a result of the balance between photochemical production and transport out of the region. The seasonal behavior at high latitudes, as evident from the springtime maxima, results from a balance between photochemical removal and transport into the region.
[Ko MKW et al; J Geophys Res (D) Atmos 94 (7): 9889-96 (1989)]**PEER REVIEWED**

REACTION BETWEEN ATOMIC OXYGEN & MOL OXYGEN RESULTS IN FORMATION OF OZONE, THE PRINCIPAL OXIDIZING AGENT OF PHOTOCHEMICAL SMOG. FURTHER REACTIONS INVOLVE OZONE & REACTIVE HYDROCARBONS (OLEFINS) TO PRODUCE MANY PRODUCTS, NATURE OF WHICH IS NOT YET FULLY KNOWN.
[Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969. 693]**PEER REVIEWED**

Environmental Abiotic Degradation:

Measurements from the eastern north Pacific stratocumulus regime have been used to study components of the regional ozone budget. The surface destruction rate was determined by eddy correlation of ozone and vertical velocity measured during 8 flights of a low flying aircraft. Significant variability (2580 to 6460 s/m) was found in the measured surface resistance; it was partially correlated with friction velocity but appears to have other controlling influences as well. The mean resistance was 4190 + or - 840 s/m, which is higher (slower destruction) than most previous estimates for seawater. Flux and mean measurements throughout the marine boundary layer were used to estimate the net rate of in situ photochemical production/destruction of ozone. Averaged over the flights, ozone concn was found to be near steady state, and a net photochemical destruction of 0.02 to 0.07 ng/cu m/sec was diagnosed. Ozone vertical distributions above the boundary layer showed a strongly layered structure with very sharp gradients.
[Kawa SR, Pearson R; J Geophys Res (D) Atmos 94 (7): 9809-17 (1989)]**PEER REVIEWED**

Atmospheric Concentrations:

The contributions of traffic related emissions to the long-term and short-term mesoscale concentrations of ozone (O3) in the The Netherlands were estimated by means of atmospheric transport models using both a Eulerian grid model with simplified chemistry and a trajectory model with a more complex chemistry. The national traffic emissions have only a minor contribution (4%) to the O3 peak values observed in the The Netherlands; European traffic emissions are estimated to be responsible for 26% of the O3 peak values, while anthropogenic emissions in Europe account for 64% of the O3 peak values.
[De Leeuw FAA; Atmos Environ 23 (1): 49-53 (1989)]**PEER REVIEWED**

Ozone (O3) concentrations were measured from 1981-83 at each of three urban stations in the cities of Edmonton and Calgary and were compared with O3 values reported earlier in rural Alberta areas. Ozone concentrations in Alberta cities typically exhibit a max in May (up to 35 ppb) and a minimum in Nov (as low as 4 ppb). This behavior is similar to that of rural Alberta O3 concentrations. Annual O3 concentrations at the urban monitoring stations vary from 11 ppb to 22 ppb and are about one-half the values at rural stations. In winter, urban O3 concentrations are always smaller than rural concentrations and the cities act as sinks for O3. Canada's hourly maximum desirable level (50 ppb) is exceeded 11 times more often at the rural stations than at the urban stations.
[Angle RP, Sandhu HS; Atmos Environ 23 (1): 215-21 (1989)]**PEER REVIEWED**

Ozone (O3) concn were monitored above a 30 m Douglas-fir canopy at Cedar River, Washington from 1 Apr to 30 Sept in 1986 and 1987. Max avg hourly O3 were similar in both yr. O3 concn exceeded 0.12 ppm on 2 days in 1986 and 1 day in 1987. Fifteen and 14 days had ozone concn > or = 0.08 ppm in 1986 and 1987, respectively. O3 concn were pos related to daily radiation and max daily air temp. Only 46% of the variance in ozone concn in 1986 could be explained by solar radiation and even less was explained by max temp (26%). In 1987, 51 and 54% of the variation in O3 concn was explained by solar radiation and temp, respectively. Max avg hourly O3 concn peaked near 1500 hr for days > 0.06 ppm with minimum values near 0600 hr. Highest concn were observed when the wind was blowing from the northwest from the Seattle area.
[Edmonds RL, Basabe FA; Atmos Environ 23 (3): 625-9 (1989)]**PEER REVIEWED**

Data collected by the Texas Air Control Board for the years 1973 through 1983 were examined to determine whether any positive relationships existed between ambient hydrocarbon concentrations and daily maximum ozone levels. When daily peak hourly average ozone concentrations and daily peak hourly average nonmethane hydrocarbon concentrations were plotted, it was demonstrated that essentially any concentration of ozone can result from any concentration of hydrocarbons. Additionally, low concentrations of hydrocarbons were not associated with concurrent low levels of ozone. At very high hydrocarbon levels, ozone levels were likely to be below the standard of 120 ppb, whereas at very low hydrocarbon levels ozone levels were likely to be high. The relationship between ozone and nitrogen oxides were examined (daily peak hourly averages) and trends similar to those with ozone and hydrocarbon concentrations were noted. Ozone concentrations tended to increase as values of the hydrocarbons to nitrogen oxides ratio decreased. Ozone concentrations increased with increasing air temperature.
[Argento VK; Chem Eng Prog 84 (12): 50-4 (1989)]**PEER REVIEWED**

Ozone concn above 80 ppb are common in the East in spring and summer.
[Logan J; J Geophys Res (D) 94 (6): 8511-32 (1989)]**PEER REVIEWED**

Ambient particulate sulfate levels at a rural site in Israel were measured intermittently over a period of more than 2 yr. Concurrent measurements of the ambient pollutant, ozone, revealed little correlation between the sulfate concentration and ozone level, although they both showed a similar diurnal and annual trend.
[Luria M et al; J Atmos Chem 8 (3): 241-50 (1989)]**PEER REVIEWED**

During late April 1987 an exceptional ozone episode occurred during which mid afternoon hourly O3 concn reached between 80 and 100 ppbV at many sites in the United Kingdom during a 5 day period. Data from the recently established U.K. network of O3 monitoring stations is used to estimate O3 concn in the mixed layer of the lower troposphere as air moves across the U.K. Detailed analyses of individual episode days have enabled estimates to be made of the contribution of 'local' photochemical O3 production to the observed concn at various U.K. sites. Ozone budgets are derived by following air columns between well mixed phases on successive days along trajectories, which take into account their variation with height. The results from 10 budget calculations show a clear relationship between the apparent generation of O3 in the mixed layer and the sunshine experienced along the respective trajectory. The apparent O3 generation values (in ppbV) for the 10 sites are 10, 7, 11, 11, 35, 31, 22, 34, 41, and 41 (+ or - from 2 to 10), while the respective hr of sunshine were 1.5, 3, 3, 4.5, 6.5, 7, 8, 9, 9.5, and 12.5. A net O3 generation of about 4 ppbV/hr of bright sunshine is indicated, implying maximum daily generations of about 45 ppbV in April and about 6O ppbV in midsummer under similar conditions.
[Weston KJ et al; Atmos Environ 23 (6): 1349-60 (1989)]**PEER REVIEWED**

A photochemical trajectory model has been employed to calculate the maximum potential from ozone generation in air parcels passing over the United Kingdom during a photochemical pollution episode in Apr 1987. In all, 11 trajectories have been studied and the model results compared against an objective analysis of the integrated ozone generation based on the observations reported from the United Kingdom Dept of the Environment ground level ozone network. There is apparently good correlation between observed ozone formation and the model ozone formation potential. Peak ozone concn found along the 11 trajectory paths studied varied from 39 to 75 ppb.
[Derwent RG; Atmos Environ 23 (6): 1361-71 (1989)]**PEER REVIEWED**

Ozone concn above 80 ppb are common in the East U.S. in spring and summer, but they are unusual in the West, and ozone shows considerably more day-to-day variability in the East. Variations in ozone levels are highly correlated over distances of several hundred kilometers in the East, indicating that high values are associated with episodes of large spatial scale, > 600,000 sq km. There were 10 and 7 such episodes in 1978 and 1979, respectively, between the mo of Apr and Sept; they persisted for 3-4 days, on avg, with a range of 2-8 days, and were most common in Jun. Daily max ozone values exceeded 90 ppb at over half the sites during these episodes and were often > 120 ppb at one or more sites. An analysis of the meteorology for each episode shows that they occurred preferentially in the presence of weak, slow-moving, and persistent high-pressure systems. Two episodes that occurred outside the summer half of the yr were associated with unseasonably warm weather; only 1 episode, in Mar 1978, appeared to reflect a major stratospheric intrusion. Concn of NOx at rural locations in the East are frequently high enough (> 1 ppb) to permit significant photochemical formation of ozone. It is clear that rural ozone in the East in spring and summer is severely impacted by anthropogenic emissions of NOx and hydrocarbons, and that ozone episodes occur when the weather is particularly conducive to photochemical formation of ozone. Ozone episodes were present on 23% of days in May-Aug in the East in 1978-1979.
[Logan JA; J Geophys Res (D) 94 (6): 8511-32 (1989)]**PEER REVIEWED**

Environmental Standards & Regulations:

CERCLA Reportable Quantities:

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Ozone is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 100 lbs.
[40 CFR 355 (7/1/97)]**QC REVIEWED**

Chemical/Physical Properties:

Molecular Formula:

O3
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1105]**PEER REVIEWED**

Molecular Weight:

48.00
[U.S. Department of Health and Human Services, Public Health Service, Center for Disease Control, National Institute for Occupational Safety Health. Registry of Toxic Effects of Chemical Substances (RTECS). National Library of Medicine's current MEDLARS file.p. 83/8211]**PEER REVIEWED**

Color/Form:

COLORLESS GAS; DARK BLUE LIQ; BLUE-BLACK CRYSTALS
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993.,p. 4-80]**PEER REVIEWED**

BLUISH GAS
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1105]**PEER REVIEWED**

Colorless to blue gas.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 94-116. Washington, D.C.: U.S. Government Printing Office, June 1994. 238]**QC REVIEWED**

Odor:

CHARACTERISTIC ODOR IN CONCN LESS THAN 2 PPM
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1105]**PEER REVIEWED**

Pungent odor
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 864]**PEER REVIEWED**

Very pungent odor.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 94-116. Washington, D.C.: U.S. Government Printing Office, June 1994. 238]**QC REVIEWED**

Boiling Point:

-111.9 DEG C
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993.,p. 4-80]**PEER REVIEWED**

Melting Point:

-192.7 + or - 2 DEG C
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993.,p. 4-80]**PEER REVIEWED**

Critical Temperature & Pressure:

CRITICAL TEMP: -12.1 DEG C; CRITICAL PRESSURE: 53.8 ATM
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1105]**PEER REVIEWED**

Density/Specific Gravity:

GAS: 2.144 G/L @ 0 DEG C; LIQ: 1.614 G/L @ -195.4 DEG C
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993.,p. 4-80]**PEER REVIEWED**

Solubilities:

49 CC/100 CC WATER AT 0 DEG C; SOL IN ALKALINE SOLVENTS, OILS
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993.,p. 4-80]**PEER REVIEWED**

Spectral Properties:

INDEX OF REFRACTION: 1.2226 (LIQ)
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 73rd ed. Boca Raton, FL: CRC Press Inc., 1992-1993.,p. 4-80]**PEER REVIEWED**

INTENSE ABSORPTION BAND BEGINNING @ ABOUT 290 NM
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1105]**PEER REVIEWED**

Other Chemical/Physical Properties:

HEAT OF FORMATION 34.4 KCAL/MOLE @ 25 DEG C; POWERFUL OXIDIZING AGENT
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1105]**PEER REVIEWED**

An allotropic form of oxygen
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 864]**PEER REVIEWED**

Chemical Safety & Handling:

Skin, Eye and Respiratory Irritations:

Irritation - eye, nose, throat, skin - Marked.
[Cralley, L.J., L.V. Cralley (eds.). Patty's Industrial Hygiene and Toxicology. Volume III: Theory and Rationale of Industrial Hygiene Practice. 2nd ed., 3A: The Work Environment. New York, NY: John Wiley Sons, 1985.177]**PEER REVIEWED**

Gas irritates the upper respiratory system strongly.
[Armour, M.A. Hazardous Laboratory Chemicals Disposal Guide. Boca Raton, FL: CRC Press Inc., 1991. 269]**PEER REVIEWED**

Fire Potential:

POWERFUL OXIDIZING AGENT ... EVOLVES MORE HEAT AND USUALLY STARTS AT A LOWER TEMPERATURE THAN OXIDATION WITH BIATOMIC OXYGEN.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 1579]**PEER REVIEWED**

Dangerous fire ... risk in contact with organic materials.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 864]**PEER REVIEWED**

Explosive Limits & Potential:

IT REACTS WITH NON-SATURATED ORGANIC COMPOUNDS TO PRODUCE OZONIDES, WHICH ARE UNSTABLE AND MAY DECOMPOSE WITH EXPLOSIVE VIOLENCE.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 1579]**PEER REVIEWED**

Pure solid or liquid is highly explosive.
[Armour, M.A. Hazardous Laboratory Chemicals Disposal Guide. Boca Raton, FL: CRC Press Inc., 1991. 268]**PEER REVIEWED**

Evaporation of a solution of ozone in liquid oxygen causes ozone enrichment and ultimately explosion. Organic liquids and oxidizable materials dropped into liquid ozone will also cause explosion of the ozone.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 3rd ed. Boston, MA: Butterworths, 1985. 1359]**PEER REVIEWED**

Passage of ozone into acetylene leads to a violent explosion when 50 mg/l of ozone is present.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 3rd ed. Boston, MA: Butterworths, 1985. 1359]**PEER REVIEWED**

Interaction /of bromine and ozone/ becomes explosive above 20 deg C and a minimum critical pressure.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 3rd ed. Boston, MA: Butterworths, 1985. 1360]**PEER REVIEWED**

Contact of ether with ozonized oxygen produces some of the explosive diethyl peroxide.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 3rd ed. Boston, MA: Butterworths, 1985. 1362]**PEER REVIEWED**

Liquid hydrogen and solid ozone form very powerfully explosive mixtures.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 3rd ed. Boston, MA: Butterworths, 1985. 1362]**PEER REVIEWED**

In an attempt to introduce carboxyl groups to improve the adhesive properties of rubber, 6 l of powdered rubber (0.1-0.5 mm particle size) in an 8 l flask was treated with ozonized oxygen. The gas stream, containing 5% of ozone was led to the bottom of the flask via a dip tube at the rate of 4 l/min for 2 min, when treatment was discontinued and the flask closed. After 5 min a violent explosion occurred.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 3rd ed. Boston, MA: Butterworths, 1985. 1363]**PEER REVIEWED**

Silica gel at -78 deg C adsorbs 4.5 wt % of ozone, and below this temperature the concentration increases rapidly. At below -112 deg C ozone liquefies and there is a potential explosion hazard at temperatures below -100 deg C if organic material is present.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 3rd ed. Boston, MA: Butterworths, 1985. 1363]**PEER REVIEWED**

Passage of oxygen containing 2% of ozone through stibine at -90 deg C caused an explosion.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 3rd ed. Boston, MA: Butterworths, 1985. 1364]**PEER REVIEWED**

Hazardous Reactivities & Incompatibilities:

All oxidizable materials (both organic and inorganic).
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 238]**QC REVIEWED**

Explosive with alkenes, aromatic compounds, bromine, combustible gasses, diethyl ether, hydrogen bromide, isopropylidene compounds.
[Armour, M.A. Hazardous Laboratory Chemicals Disposal Guide. Boca Raton, FL: CRC Press Inc., 1991. 268]**PEER REVIEWED**

Dangerous /fire hazard/ by chemical reaction with aniline, benzene, bromide, (diallyl methyl carbinol + acetic acid), diethyl ether, nitrogen pentoxide, ethylene, hydrogen bromide, hydrogen iodide, nitrogen dioxide, nitric oxide, nitrogen chloride, NI3, nitroglycerin, organic liquids, organic matter, antimony.
[Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984. 2111]**PEER REVIEWED**

/Other/ incompatabilities: Alkenes, aromatic compounds, rubber, dicyanogen, dinitrogen tetroxide, 4-hydroxy-4-methyl-1,6-heptadiene, nitrogen trichloride, stibine, tetrafluorohydrazine.
[Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984. 2111]**PEER REVIEWED**

Immediately Dangerous to Life or Health:

5 ppm
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 238]**QC REVIEWED**

Protective Equipment & Clothing:

WORKERS HANDLING LIQ OZONE SHOULD WEAR PROTECTIVE EQUIPMENT DESIGNED FOR EXPOSURE TO CRYOGENIC LIQ, EG GLOVES MADE FROM PLASTICS OR ASBESTOS, EYE & FACE PROTECTION.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 1580]**PEER REVIEWED**

Recommendations for respirator selection. Max concn for use: 1 ppm. Respirator Class(es): Any chemical cartridge respirator with cartridge(s) providing protection against the compound of concern. Only nonoxidizable sorbents are allowed (not charcoal). Any supplied-air respirator.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 238]**QC REVIEWED**

Recommendations for respirator selection. Max concn for use: 2.5 ppm. Respirator Class(es): Any supplied-air respirator operated in a continuous flow mode. Any powered, air-purifying respirator with cartridge(s) providing protection against the compound of concern. Only nonoxidizable sorbents are allowed (not charcoal).
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 238]**QC REVIEWED**

Recommendations for respirator selection. Max concn for use: 5 ppm. Respirator Class(es): Any chemical cartridge respirator with a full facepiece and cartridge(s) providing protection against the compound of concern. Only nonoxidizable sorbents are allowed (not charcoal). Any air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted canister providing protection against the compound of concern. Only nonoxidizable sorbents are allowed (not charcoal). Any supplied-air respirator that has a tight-fitting facepiece and is operated in a continuous-flow mode. Any self-contained breathing apparatus with a full facepiece. Any supplied-air respirator with a full facepiece.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 238]**QC REVIEWED**

Recommendations for respirator selection. Condition: Emergency or planned entry into unknown concn or IDLH conditions: Respirator Class(es): Any self-contained breathing apparatus that has a full facepiece and is operated in a pressure-demand or other positive pressure mode. Any supplied-air respirator with a full facepiece and operated in pressure-demand or other positive pressure mode in combination with an auxiliary self-contained breathing apparatus operated in pressure-demand or other positive pressure mode.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 238]**QC REVIEWED**

Recommendations for respirator selection. Condition: Escape from suddenly occurring respiratory hazards: Respirator Class(es): Any air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted canister providing protection against the compound of concern. Only nonoxidizable sorbents are allowed (not charcoal). Any appropriate escape-type, self-contained breathing apparatus.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 238]**QC REVIEWED**

Preventive Measures:

PROCESSES EMPLOYING OZONE SHOULD BE TOTALLY ENCLOSED OR SO EQUIPPED WITH EXHAUST VENTILATION. ... ALL ELECTRICAL EQUIPMENT SHOULD BE SUITABLY INSULATED.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 1580]**PEER REVIEWED**

Contact lenses should not be worn when working with this chemical.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 238]**QC REVIEWED**

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.
**PEER REVIEWED**

Stability/Shelf Life:

UNSTABLE GAS ... @ NORMAL TEMP DECOMP TO BIATOMIC OXYGEN. ... IN LIQ OR SOLID PHASE PARTICULARLY UNSTABLE.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 1579]**PEER REVIEWED**

ALTHOUGH STABILITY OF OZONE IN AQ SOLN DECR AS ALKALINITY RISES, THIS EFFECT IS REVERSED @ HIGH CONCN; T/2 OF OZONE IS 2 MIN IN 1 N SODIUM HYDROXIDE; IT IS INCR TO 83 HR IN 20 N SODIUM HYDROXIDE
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1105]**PEER REVIEWED**

Liquefiable at -12 deg C.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 864]**PEER REVIEWED**

Storage Conditions:

CYLINDERS OF DISSOLVED OZONE SHOULD BE STORED IN REFRIGERATED AREAS & AWAY FROM ALL REDUCING AGENTS, FLAMMABLE MATERIALS & SUBSTANCES SUCH AS IRON, COPPER OR CHROMIUM THAT MAY CATALYZE DECOMP.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 1580]**PEER REVIEWED**

Store in well-ventilated, cool, dark places. Detached storage is preferred. Avoid storage near combustible materials.
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 393]**PEER REVIEWED**

Disposal Methods:

Evaporation: Provide ventilation to dilute and disperse small amt of ozone into the outside atmosphere.
[United Nations. Treatment and Disposal Methods for Waste Chemicals (IRPTC File). Data Profile Series No. 5. Geneva, Switzerland: United Nations Environmental Programme, Dec. 1985. 220]**PEER REVIEWED**

In the fume hood, wastes to be slowly released to air.
[Armour, M.A. Hazardous Laboratory Chemicals Disposal Guide. Boca Raton, FL: CRC Press Inc., 1991. 269]**PEER REVIEWED**

Occupational Exposure Standards:

OSHA Standards:

Permissible Exposure Limit: Table Z-1 8-hr Time Weighted Avg: 0.1 ppm (0.2 mg/cu m).
[29 CFR 1910.1000 (7/1/98)]**QC REVIEWED**

Vacated 1989 OSHA PEL TWA 0.1 ppm (0.2 mg/cu m); STEL 0.3 ppm (0.6 mg/cu m) is still enforced in some states.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 369]**QC REVIEWED**

Threshold Limit Values:

8 hr Time Weighted Avg (TWA): 0.05 ppm, heavy work; 0.08 ppm, moderate work; 0.1 ppm, light work; 0.20 ppm, heavy, moderate, or light workloads of </=2 hours.
[American Conference of Governmental Industrial Hygienists. TLVs & BEIs: Threshold limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2002. Cincinnati, OH. 2002.46]**QC REVIEWED**

Excursion Limit Recommendation: Excursions in worker exposure levels may exceed three times the TLV-TWA for no more than a total of 30 min during a work day, and under no circumstances should they exceed five times the TLV-TWA, provided that the TLV-TWA is not exceeded.
[American Conference of Governmental Industrial Hygienists. TLVs & BEIs: Threshold limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2002. Cincinnati, OH. 2002.6]**QC REVIEWED**

A4; Not classifiable as a human carcinogen. /Heavy work, moderate work, light work, or heavy, moderate, or light workloads (</=2 hours)/
[American Conference of Governmental Industrial Hygienists. TLVs & BEIs: Threshold limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2002. Cincinnati, OH. 2002.46]**QC REVIEWED**

NIOSH Recommendations:

Recommended Exposure Limit: Ceiling Value: 0.1 ppm (0.2 mg/cu m).
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 238]**QC REVIEWED**

Immediately Dangerous to Life or Health:

5 ppm
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 238]**QC REVIEWED**

Manufacturing/Use Information:

Major Uses:

AS DISINFECTANT FOR AIR AND WATER BY VIRTUE OF ITS OXIDIZING POWER. FOR BLEACHING WAXES, TEXTILES, OILS. IN ORGANIC SYNTHESES.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1105]**PEER REVIEWED**

OZONOLYSIS OF UNSATURATED FATTY ACIDS TO PELARGONIC ACID, AZELAIC ACID & TO OTHER ACIDS; OXIDATION OF FURNACE CARBON BLACK FOR INK BLACK MFR; CATALYST IN PRODN OF PEROXYACETIC ACID; WATER TREATMENT FOR TASTE & ODOR CONTROL; MOLD & BACTERIA INHIBITOR IN COLD STORAGE.
[SRI]**PEER REVIEWED**

Used as an oxidizing agent in the organic chemical industry (eg, production of azelaic acid); as a disinfectant for food in cold storage rooms; ... for bleaching ... flour, paper pulp, starch, and sugar; for aging liquor and wood; for processing certain perfumes, vanillin, and camphor; in treating industrial wastes; in the rapid drying of varnishes and printing inks; and in the deodorizing of feathers.
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 682]**PEER REVIEWED**

Deodorization of air and sewage gases, ... production of peroxides, bactericide.... Steroid hormones, removal of chlorine from nitric acid, oxidation of phenols and cyanides.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 864]**PEER REVIEWED**

Manufacturers:

Henkel of America Inc, Hq, The Triad, Suite 200, 2200 Renaissance Blvd, Gulf Mills, PA 19406, (215) 270-8100; Subsidiary: Henkel Corp, (address same as Hq), Emery Group, 11501 Northlake, PO Box 429557, Cincinnati, OH 45249; Western Operations, 5568 East 61st St, City of Commerce, CA 90022; Production site: Cincinnati, OH 45202
[SRI. 1992 Directory of Chemical Producers-United States of America. Menlo Park, CA: SRI International, 1992. 821]**PEER REVIEWED**

Methods of Manufacturing:

IN THE LAB OZONE IS PREPD BY PASSING DRY AIR BETWEEN TWO PLATE ELECTRODES CONNECTED TO AN ALTERNATING CURRENT SOURCE OF SEVERAL THOUSAND VOLTS. THE REACTION IS REVERSIBLE, & AFTER A LITTLE OZONE HAS BEEN PRODUCED IT IS DECR AT THE SAME RATE AS IT IS GENERATED. OBTAINED IN PURE FORM BY COOLING OZONIZED AIR TO -180 DEG C WHEN IT SEPARATES AS A DARK BLUE LIQ.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1105]**PEER REVIEWED**

COMMERCIAL MIXT CONTAINING UP TO 2% OZONE ARE PRODUCED BY ELECTRONIC IRRADIATION OF AIR. IT IS USUALLY MFR ON THE SPOT, AS IT IS TOO EXPENSIVE TO SHIP. TONNAGE QUANTITIES ARE USED.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 864]**PEER REVIEWED**

Ozone is prepared by the heating of silver difluoride in a dilute aqueous acid
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984.,p. V10 796 (1980)]**PEER REVIEWED**

General Manufacturing Information:

DETERIORATION OF RUBBER IS ACCELERATED BY TRACES OF OZONE.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 864]**PEER REVIEWED**

OZONE IS A HIGHLY EFFICIENT DISINFECTANT WHICH MAY HAVE SIGNIFICANT ADVANTAGES IN WATER TREATMENT COMPARED TO CHLORINE. IT HAS, HOWEVER, BEEN SHOWN THAT MUTAGENIC & POSSIBLY CARCINOGENIC BY-PRODUCTS MAY BE PRODUCED UNDER CERTAIN CONDITIONS OF OZONATION. LIGHT CHLORINATION FOLLOWING OZONIZATION MAY MEET THE HIGHEST STANDARDS OF WATER DISINFECTION. IN MANY CASES OZONE TREATMENT ALONE MAY SUFFICE.
[CARMICHAEL NG ET AL; MINIREVIEW: THE HEALTH IMPLICATIONS OF WATER TREATMENT WITH OZONE; LIFE SCI 30(2) 117 (1982)]**PEER REVIEWED**

Contributes to formation of photochemical smog.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993 864]**PEER REVIEWED**

The ozone generation rate and particle size dependent (0.01-10 micrometers) filtration efficiency of an in-duct residential electronic air cleaner were measured. Filtration efficiencies were typically 70-90%, showing decreasing efficiency with increasing flowrate. Ozone generation rates were about 3 ug/s. Scans of the aerosol concn on the downwind face of the electronic air cleaner were used to locate, then eliminate, areas of aerosol sneakage. Sneakage was detected along the top and bottom of the electronic air cleaner face, apparently due to incomplete aerosol charging for aerosol passing near the ends of the ionizing wires. Areas away from the top and bottom had near-zero aerosol penetration. Based on these results, the inlet to the electronic air cleaner was masked to eliminate airflow through the sneakage areas. The resultant efficiency of the masked electronic air cleaner was nearly 100% for particles larger than 0.1 micrometer diameter; however, the filtration efficiency for particles smaller than 0.1 um was not significantly affected by masking.
[Hanley J et al; Govt Reports Announcements & Index (GRA&I), Issue 14 (1991)]**PEER REVIEWED**

U. S. Production:

(1966) 5.45X10+9 GRAMS (EST)
[SRI]**PEER REVIEWED**

Laboratory Methods:

Analytic Laboratory Methods:

NIOSH Method S8. Analyte: Ozone. Matrix: Air. Procedure: Potassium iodide method. Method Evaluation: Method was validated over the range of 0.1 to 0.4 mg/cu m using a 45 liter sample. Method detection limit: Not determined. Precision (CVT): 0.0806. Applicability: Under the conditions of sample size (not given) the useful range is not determined. Interferences: Chlorine, hydrogen peroxide, organic peroxides, and various other oxidants will liberate iodine by this method. Negative interferences from reducing gases such as sulfur dioxide and hydrogen sulfide are very serious (probably on a mole to mole equivalency).
[U.S. Department of Health, Education Welfare, Public Health Service. Center for Disease Control, National Institute for Occupational Safety Health. NIOSH Manual of Analytical Methods. 2nd ed. Volumes 1-7. Washington, DC: U.S. Government Printing Office, 1977-present.p. V2 S8-1]**PEER REVIEWED**

NIOSH Method 153. Analyte: Ozone. Matrix: Air. Procedure: Potassium iodide absorption--colorimetric. Method Evaluation: Method was validated over the range of 0.01 to 10 ppm using a 10 ml sample. Method detection limit: Not determined. Precision (CVT): + or - 5%. Applicability: Under the conditions of sample size (not given) the useful range is not determined. Interferences: Negative interfer interferences are sulfur dioxide and hydrogen sulfide.
[U.S. Department of Health, Education Welfare, Public Health Service. Center for Disease Control, National Institute for Occupational Safety Health. NIOSH Manual of Analytical Methods. 2nd ed. Volumes 1-7. Washington, DC: U.S. Government Printing Office, 1977-present.p. V1 153-1]**PEER REVIEWED**

NIOSH Method 154. Analyte: Ozone. Matrix: Air. Procedure: Colorimetric alkaline potassium iodide method. Method Evaluation: Method was validated over the range of 0.1 to 0.4 mg/cu m using a 45 liter sample. Method detection limit: 0.04 mg/cu m. Precision (CVT): 0.08. Applicability: Under the conditions of sample size (not given) the useful range is not validated. Interferences: Chlorine, hydrogen peroxide, organic peroxides, and various other oxidants will liberate iodine by this method.
[U.S. Department of Health, Education Welfare, Public Health Service. Center for Disease Control, National Institute for Occupational Safety Health. NIOSH Manual of Analytical Methods. 2nd ed. Volumes 1-7. Washington, DC: U.S. Government Printing Office, 1977-present.p. V1 154-1]**PEER REVIEWED**

CAN BE MEASURED DIRECTLY IN ATMOSPHERE BY ... KRUGER UV PHOTOMETER.
[Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969. 707]**PEER REVIEWED**

After syringe extraction of air-ozone samples (10 ml) from a reactor via a Teflon septum, samples were injected immediately into a bottle containing potassium indigo trisulfonate (PITS) solution (10 ml, 1x10-4 M) and shaken for a minimum of 20 sec. Light absorption of the samples were measured at 600 nm to calculate the amount of gas-phase ozone in the reactor. Comparison of average ozone concn data from real-time indigo and iodometric methods for both reactor influent and effluent resulted in a correlation coefficient (r) of 0.991, and no difference at the 90% confidence level (Student's t test). Ozone concn tested ranged from 0.59-4.10 mg/l.
[Collins AG et al; Ozone Sci Eng 11 (1): 115-26 (1989)]**PEER REVIEWED**

The iodometric method for determination of ozone in a gas stream was compared with a spectrophotometric ozone monitor as the referee method. Three variations were investigated: a modification of the neutral buffered potassium iodide method, the unbuffered potassium iodide method, and the Masschelein modification of the neutral buffered potassium iodide method. The neutral buffered method always produced higher values (average of 15%) of ozone concentrations than did the other two potassium iodide methods. In the neutral buffered method, iodine production continued after the initial reaction of ozone with iodide, as much as 6.8% additional iodine during the subsequent 60 min, compared with about 1% with the other two methods. Variation of the gas flow rate (normal and 60% reduction) showed that greater flow rates yielded higher ozone concentrations. This effect was more dramatic in the unbuffered potassium iodide method and in the weakly buffered Masschelein modification. The effect of the flow rate was least for the most strongly buffered reagent.
[Gordon G et al; J Am Water Works Assoc 81 (6): 72-6 (1989)]**PEER REVIEWED**

A spectrophotometric method for the determination of residual ozone (O3) in water, using the dye, Acid Chrome Violet K (CI Nr 61710; Alizarin Violet 3R), is described. The decolorization of Acid Chrome Violet K at 548 nm in an ammonia-ammonium chloride (NH3-NH4Cl) buffer solution of pH 8.1 to 8.5 is specific for (O3) without interference from chlorine, chloramines, chlorite or chlorate ions in concentrations likely to be present in treated drinking water. The detection limit for O3 using this method is 0.02 mg/l, with a standard deviation of 0.01 mg/l.
[Masschelein WJ et al; Ozone Sci Eng 11: 209-15 (1989)]**PEER REVIEWED**

Emission of ozone and dust from laser printers; presentation of a new emission source test method.
[Eggert T et al. U.S. EPA'S Atmospheric Research & Exposure Assessment Laboratory and Air and Waste Management Association. Measurement of Toxic and Related Air Pollutants; International Symposium, Raleigh, NC, USA, May 1-4, 1990. Xxi+1097p. Air and Waste Management association: Pittsburgh, PA, USA. 0 (0): 1061-72 (1990)]**PEER REVIEWED**

Sampling Procedures:

NIOSH Method S8. Analyte: Ozone. Matrix: Air. Procedure: Colorimetric-Alkaline. Flow Rate: 1 l/min. Sample Size: 45 liters.
[U.S. Department of Health, Education Welfare, Public Health Service. Center for Disease Control, National Institute for Occupational Safety Health. NIOSH Manual of Analytical Methods. 2nd ed. Volumes 1-7. Washington, DC: U.S. Government Printing Office, 1977-present.p. V2 S8-1]**PEER REVIEWED**

NIOSH Method 153. Analyte: Ozone. Matrix: Air. Procedure: Potassium iodide absorption--colorimetric. Flow Rate: 1-2 l/min. Sample Size: 10 ml.
[U.S. Department of Health, Education Welfare, Public Health Service. Center for Disease Control, National Institute for Occupational Safety Health. NIOSH Manual of Analytical Methods. 2nd ed. Volumes 1-7. Washington, DC: U.S. Government Printing Office, 1977-present.p. V1 153-1]**PEER REVIEWED**

NIOSH Method 154. Analyte: Matrix: Air. Procedure: Collection via impinger. FlowRate: 1 l/min. Sample Size: 10 ml.
[U.S. Department of Health, Education Welfare, Public Health Service. Center for Disease Control, National Institute for Occupational Safety Health. NIOSH Manual of Analytical Methods. 2nd ed. Volumes 1-7. Washington, DC: U.S. Government Printing Office, 1977-present.p. V1 154-1]**PEER REVIEWED**

Special References:

Special Reports:

MENZEL DB; METABOLIC EFFECTS OF OZONE EXPOSURE; ADV MOD ENVIRON TOXICOL 5(INT SYMP BIOMED EFFECTS OZONE RELAT PHOTOCHEM OXIDN) 47 (1983). A REVIEW WITH 15 REFERENCES ON METABOLIC EFFECTS OF OZONE EXPOSURE.

CHOW CK; INFLUENCE OF DIETARY VITAMIN E ON SUSCEPTIBILITY TO OZONE EXPOSURE; ADV MOD ENVIRON TOXICOL 5(INT SYMP BIOMED EFFECTS OZONE RELAT PHOTOCHEM OXIDN) 75 (1983). A REVIEW WITH 50 REFERENCES ON THE INFLUENCE OF VITAMIN E ON THE TOXICITY OF OZONE.

FOLINSBEE LJ; EFFECTS OF OZONE EXPOSURE ON LUNG FUNCTION IN MAN: A REVIEW; REV ENVIRON HEALTH 3 (3): 211 (1981). A REVIEW ON THE EFFECTS OF OZONE ON HUMAN LUNG FUNCTION ARE DISCUSSED WITH PARTICULAR ATTENTION TO LEVELS WHICH ARE NEAR THE THRESHOLD OF PRODUCING NO EFFECT.

Menzel DB; Antioxidant Vitamins and Prevention of Lung Disease. Ann N Y Acad Sci669: 141-55 (1992).

Mortensen LM; Effects of Ozone on Growth of Several Subalpine Plant Species. Norw J Agric Sci 7 (2): 129-38 (1993).

Mustafa MG; Biochemical Basis of Ozone Toxicity. Free Radic Biol Med 9 (3): 245-65 (1990).

Victorin K; Review of the Genotoxicity of Ozone. Mutat Res 277 (3): 221-38 (1992).The genotoxicity of ozone was reviewed with respect to: the reaction of ozone with DNA and RNA; genotoxic potential in microorganisms, plants, and insects; cell culture study results including cytogenetic effects, effects on DNA, cell transformation in vitro, and data evaluation; in vivo genotoxicity in animal experiments including Chinese hamsters, C3H mice, C47BL/6 mice, and F334/N rats; and cytogenetic potential in humans from experiments demonstrating chromosome type aberrations, chromatid type aberrations, sister chromatid exchange, and other types of chromosome and chromatid type aberrations.

Toxicology & Carcinogenesis Studies of Ozone and Ozone/NNK in F344/N Rats and B6C3F1 Mice (Inhalation Studies). Technical Report Series No. 440 (1994) NTIS Publication No. 95-226999 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709

Synonyms and Identifiers:

Synonyms:

OXYGEN, MOL (O3)
**PEER REVIEWED**

OZON (POLISH)
**PEER REVIEWED**

TRIATOMIC OXYGEN
**PEER REVIEWED**

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