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EC number: 233-069-2 | CAS number: 10028-15-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Epidemiological data
Administrative data
- Endpoint:
- epidemiological data
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 011
Materials and methods
- Study type:
- other: controlled exposure of human subjects
- Endpoint addressed:
- acute toxicity: inhalation
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Research study with controled exposure to human subject
- GLP compliance:
- no
Test material
- Reference substance name:
- Ozone
- EC Number:
- 233-069-2
- EC Name:
- Ozone
- Cas Number:
- 10028-15-6
- Molecular formula:
- O3
- IUPAC Name:
- trioxygen
- Test material form:
- gas
Constituent 1
- Specific details on test material used for the study:
- Ozone was generated by a silent electric discharge method (Model 502; Meckenheim, Bonn, Germany)
Method
- Type of population:
- other: human volunteers
- Ethical approval:
- confirmed, but no further information available
- Details on study design:
- Each subject was exposed to clean air and 0.06 ppm ozone for 6.6 hours with moderate exercise in a stainless steel chamber (4 x 6 x 3.2 m). Exposures were randomized, double-blinded, and separated by at least 1 week. Minute ventilation (VE) was measured hourly and exercise levels adjusted to VE = 20 L/min/m2 body surface area to ensure that subjects breathed consistently throughout exposure. Spirometric lung function and symptom scores were assessed immediately before and after the 6.6- hour exposure period. Sputum was collected the next morning approximately 16 to 18 hours postexposure. Exposures were conducted only during the cool weather season in Chapel Hill (November–March) to minimize exposure to elevated ambient ozone.
- Exposure assessment:
- measured
- Details on exposure:
- Ozone was generated by a silent electric discharge method (Model 502; Meckenheim, Bonn, Germany) and introduced into the chamber that was maintained at 22 6 1.08C and 40 6 5% relative humidity. The concentration of ozone was continuously monitored using ultraviolet photometric analyzers (TECO Model 49; Thermo Scientific, Franklin, MA) that were periodically calibrated for 6 5% accuracy by NIST traceable ozone calibrator (TECO Model 49PS).
- Statistical methods:
- The lung function endpoints were expressed as percent changes from the preexposure (or baseline) values for each subject. Neutrophil content in the sputum samples was expressed as percent of total cell count (%PMN) and the measurements after each exposure were compared. Linear mixed-effects models with a subject-specific random intercept was used to test changes in response endpoints between clean air and ozone exposures at the group level to account for subject-level variability and repeated measures. The effect of GSTM1 and separately sex was examined using a two-factor mixed-effects model with repeated measures on a single factor, exposure and subject-level random effects. We report the magnitude and direction of the expected change along with its associated 95% equal two-tail confidence intervals. R statistical software (Version 2.10.1) was used for the analyses. α of 0.05 was used to determine statistical significance.
Results and discussion
- Results:
- The study provides suportive information, that exposure of healthy young adults to 0.06 ppm ozone for 6.6 hours causes a significant decrement of FEV1 and an increase in neutrophilic inflammation in the airways.
Any other information on results incl. tables
Exercise and Minute Ventilation:
Means of six hourly measurements of VE, VT, breathing frequency, and heart rate during 6.6-hour exposure to CA and ozone were determined. Overall, there was no difference in both ventilation parameters and heart rates between CA and 0.06 ppm ozone exposure.
Exposure to 0.06 ppm Ozone Causes Decrements in Lung Function:
The primary hypothesis tested in this study was that exposure to 0.06 ppm ozone would decrease FEV1 and FVC after 6.6 hours. Exposure to ozone resulted in a 1.71 ± 0.50% (mean ± SEM) decrease in FEV1 compared with virtually no change (0.002 ± 0.46%) after exposure to CA. Thus, relative to CA, exposure to 0.06 ppm ozone for 6.6 hours resulted in a 1.71 ± 0.64% decrement in FEV1 (P = 0.008). These decrements did not appear to be driven by a small subset of subjects. Of the 59 individuals studied, only three subjects showed greater than 10% drop after ozone exposure. Similarly, FVC decreased by 2.32 ± 0.41% after ozone exposure versus 1.13 ± 0.34% after CA. Ozone exposure thus caused a relative decrement of 1.19 ± 0.51% (P = 0.02). Again, individual response to ozone exposure was mostly within 6 5% change. Changes in other lung function parameters (forced expiratory flow between 25% and 75% of FVC, maximum forced expiratory flow, and sRaw) were not significant. A second aim of the study was to determine the role of GSTM1 in determining responses to ozone. Although both genotypes had decrements in FEV1 after ozone exposure relative to air, changes were only statistically significant for GSTM1-positive subjects. However, the difference in FEV1 response between GSTM1-null and -positive subjects was not statistically significant (P = 0.72). Similarly, females had a significant decrement in CA-adjusted FEV1 (1.93± 0.88%, P = 0.02), whereas males did not (1.45 ± 0.95%, P = 0.14), but the difference between sexes was not significant (P = 0.66). No differences between GSTM1-null versus -positive and males versus females were seen for FVC.
Exposure to 0.06 ppm Ozone Causes Pulmonary Inflammation:
This study is the first to examine ozone concentrations below the current standard to cause pulmonary inflammation. The results are summarized in Table 4. Graphic illustration in Figure 3A shows that ozone exposure alters the airway milieu as evidenced by increases in %PMN in induced sputum samples. After air exposure, %PMN averaged 38.3 ± 3.7%. In contrast, ozone exposed samples averaged 54.0 ± 4.6%. Thus, relative to clean air, ozone exposure resulted in a 15.7 ± 3.1% increase in%PMN for the whole group (P < 0.002). Of the 24 subjects studied, all but 5 subjects showed an ozone-induced increase in %PMNs and 10 showed greater than or equal to 20% increase. A significant increase in ozone-induced %PMN for both GSTM1-null (20.0%; 95% CI, 11.0–29.0; P = 0.001) and GSTM1-positive subjects (11.3%; 95% CI, 2.3–20.3; P = 0.02) was determined. Those carrying the null allele had a stronger response (P = 0.001) than those carrying the positive allele (P= 0.02); however, the estimate of the modifying effect of GSTM1 did not reach significance (P = 0.17; also see Table 4). Both males (24.2%; 95% CI, 15.8–32.6; P = 0.001) and females (8.5%; 95% CI, 0.79–16.20; P = 0.03) had statistically significant increases in ozone-induced %PMNs. The modifying effect of sex was significant (P = 0.009). The changes in %PMN were not accompanied by changes in total cell numbers for the whole group or any subgroup after ozone versus air. Total cell counts in sputum samples were 5.05 (± 0.82) 3 106 after CA and 6.93 (± 1.52) 3 106 after ozone (P = not significant [NS] vs. CA) for the whole group.
Symptom Questionnaire:
Of 56 subjects who had no symptoms at baseline, 20 subjects reported symptoms after either CA or 0.06 ppm ozone exposure. The most commonly reported symptom was throat irritation followed by shortness of breath, pain on deep inspiration, and cough. The mean (± SEM) total symptom score was 0.43 ± 0.11 for CA and 0.41 ± 0.11 for ozone (P = NS versus CA). For genotype subgroups, total symptom score was 0.40 ± 0.16 for CA and 0.47 ± 0.17 for ozone in GSTM1-positive subjects and 0.46 ± 0.16 for CA and 0.35 ± 0.13 for ozone in GSTM1-null subjects (P = NS versus CA for both groups). The score and nature of the symptoms were similar between CA and ozone exposures.
Applicant's summary and conclusion
- Conclusions:
- The study provides supportive information, that exposure of healthy young adults to 0.06 ppm ozone for 6.6 hours causes a significant decrement of FEV1 and an increase in neutrophilic inflammation in the airways.
- Executive summary:
In this human volunteer study the authors examined whether airway effects occur below the current ozone standard and if they are more pronounced in potentially susceptible individuals, such as those deficient in the antioxidant gene glutathione S-transferase mu 1 (GSTM1). Pulmonary function and subjective symptoms were measured in 59 healthy young adults (19–35 yr) immediately before and after exposure to 0.0 (clean air,CA) and 0.06 ppm ozone for 6.6 hours in a chamber while undergoing intermittent moderate exercise. The polymorphonuclear neutrophil (PMN) influx was measured in 24 subjects 16 to 18 hours postexposure. Subjects experienced a significantly greater (P = 0.008) change in FEV1 ( ± SE) immediately after exposure to 0.06 ppm ozone compared with CA (21.71 ± 0.50% vs. 20.002 ± 0.46%). The decrement in FVC was also greater (P = 0.02) after ozone versus CA (22.32 ± 0.41% vs. 21.13 ± 0.34%). Similarly, changes in %PMN were greater after ozone (54.0 ± 4.6%) than CA (38.3 ± 3.7%) exposure (P < 0.001). Symptom scores were not different between ozone versus CA. There were no significant differences in changes in FEV1, FVC, and %PMN between subjects with GSTM1-positive and GSTM1-null genotypes. Exposure of healthy young adults to 0.06 ppm ozone for 6.6 hours causes a significant decrement of FEV1 and an increase in neutrophilic inflammation in the airways. GSTM1 genotype alone appears to have no significant role in modifying the effects.
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