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Diss Factsheets

Administrative data

additional toxicological information
Type of information:
other: handbook data
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Reference Type:
review article or handbook
Patty´s toxicology
Bingham E.; Cohrssen B.; Patty F.A.
Bibliographic source:
page 994-1001; Wiley-Blackwell (an imprint of John Wiley & Sons Ltd) (4. September 2012); ISBN-10: 0470410817

Materials and methods

Type of study / information:
Handbook data on animal and epidemiological data

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Test material form:

Results and discussion

Any other information on results incl. tables

Chronic and Subchronic Toxicity.

One of the principal uncertainties about ozone toxicity is the relationship between repeated exposures and chronic lung disease. Guinea pigs and rats exposed to high ozone concentrations (>1000 ppb) for over 8 months developed chronic bronchiolitis, with bronchiolar fibrosis, pneumonitis, “mild to moderate”emphysema, and occasional lesions in the trachea and major bronchi. Exposure of rats to lower ozone

concentrations (120–250 ppb) resulted in less severe alteration of the terminal bronchioles and alveolar septa, and a distribution of inflammation similar to that observed in shorttermexposures. The lungs of monkeys following chronic exposures manifested bronchiolitis, altered epithelial cell proliferation, nasal secretory hyperplasia, and other effects, including focal lung lesions, which persisted after the cessation of exposure. Thus, unlike the case of acute ozone exposure, effects of chronic exposure become irreversible. After 3 months, the degree of neutrophilic inflammation was less than that observed after the first

week, suggesting that this is a transient response when concentrations are lowered. Nonetheless, monocytic inflammation persists during long-term exposures. A major finding from animal experiments is that chronic exposure to ozone concentrations found in urban air can result in persistent inflammation and small-airway structural changes. Other lines of evidence support the concept that repeated ozone exposure may result in chronic lung disease. Ozone inactivates lysozyme, an antimicrobial protein secreted by airway cells, and human a1-antitrypsin, a protease inhibitor that protects the lung from emphysema. It also increases the synthesis, deposition, and degradation of collagen in rat lung.

Human Exposure

In human studies, acute exposure to as little as 80 ppb ozone can induce neutrophilic inflammation, peaking in bronchoalveolar lavage fluid or biopsies of the bronchial mucosa 12–18 h after a single exposure. These data indicate that the acute inflammatory damage of ozone repeatedly demonstrated in animals is likely to be duplicated in the human lung at concentrations lower than those used in animal studies. In addition, chronic pathological effects have been noted in lung specimens from accident victims in southern California. More than 25% of the tissues examined had severe and extensive injury to the centriacinar region (with monocytic infiltrates).

Reaction of Ozone with Biological Macromolecules.

At concentrations,200 ppb, most, if not all, ozone is likely to react with the biological macromolecules in the respiratory lining fluid. Ozone is a powerful oxidant and will react with amino acids (particularly cysteine, tryptophan, methionine, phenylalanine, and tyrosine) and with lipids (particularly the unsaturated fatty acids contained in membrane phospholipids). The former can yield disulfides and methionine sulfoxide; the latter can yield hydrogen peroxide, aldehydes, and hydroxyhydroperoxides. Antioxidants in mucus and other fluids lining the respiratory tract, as well as those in the tissues themselves, may be protective. In the past, ozone has been purported to act as a free radical. However, although clearly a strong oxidant, ozone is not a free radical. In addition, supportive evidence for this mechanism at best is only indirect and comes from studies showing that vitamin E, a free radical scavenger, retards or prevents ozone’s effects on polyunsaturated fatty acids in vitro. In addition, vitamin E deficiency in experimental animals enhances ozone’s toxicity. It is not known, however, whether supplemental vitamin E in the diet can protect humans against ozone’s effects.

Applicant's summary and conclusion

Executive summary:

Patty´s toxicology is a well-known and accepted handbook. In citied chapter, animal and human data on the toxicoligcal profile of ozone is summarized.