Experts in ToxicologyHomeHome
Home PageAbout UsContact UsToxicology SupportProduct SafetyToxicology TopicsOther ServicesDr. Richard A. Parent

Causation Reports

Ozone Report


Reviews covering various aspects of ozone toxicity have been published by Lippman, Mustafa and the US EPA, but there are a number of controlled studies in man which should be noted. Gong, et al. was able to demonstrate decrements in pulmonary function parameters as well as bronchial hyperreactivity in both healthy subjects and those with chronic obstructive pulmonary disease (COPD) when exposed to ozone while Peden, et al., showed nasal inflammation and increased sensitivity to allergens in the airway mucosa of allergic asthmatics. Aris, et al., exposed healthy athletes to 0.2 ppm ozone for four hours during moderate exercise. Eighteen hours after exposure ceased, bronchial biopsies were conducted and histologic evidence of upper airway inflammation was discovered. These findings included increased neutrophils in the airway mucosa and increases in LDH ( lactate dehydrogenase ), IL-8 (interleukin-8), total cells, and epithelial cells in the proximal airways lavage fluid which caused them to conclude that ozone can cause injury to proximal airways and distal lung tissue.

Follinsbee, et al., and Horvath, et al., exposed sedentary subjects to 0.12 ppm (120 ppb) ozone with exercise, and this resulted in significant deficits in flows, tidal volumes, FVC (forced vital capacity), FEV1 (forced expiratory volume in one second), and specific airways resistance as well as symptoms of cough, pain on deep inspiration, shortness of breath, throat irritation, and wheezing. Adams exposed subjects to 80 ppb ozone for 6.6 hours and demonstrated a decrease in FEV1, while McDonnell18 reported reductions in FVC, FEV1, and FEV25-75 in 60 young adults exposed to identical conditions. Also using a similar exposure scenario, Horstman, et al., reported a significant increased response to methacholine challenge in exposed subjects. FEV1 decrements have been reported at concentrations as low as 80 ppb in controlled studies and as low as 40 ppb in adults and 23ppb in children during ambient exposures.

Another study looked at sputum analysis after ozone exposure and found neutrophils and myeloperoxidase in healthy subjects exposed to 0.4 ppm for two hours, in addition to IL-6 and IL-8. Bronchioalveolar lavage fluid (BAL) in relation to ozone exposure has been the subject of other studies. Koren, et al.,21 exposed 11 healthy non-smoking subjects to a single exposure of 0.4 ppm ozone for two hours with intermittent exercise. They found increased levels of inflammatory cells, prostaglandins, fibronectin, and increased tissue factor in the lower airways of exposed subjects.

Graham and Koren exposed ten subjects to 0.4 ppm ozone with exercise for 2 hours and found significant numbers of PMNs (polymorphonuclear leukocytes) in nasal lavage and considered this to be a good predictor of acute inflammatory response. In a 1995 publication, Weinmann, et al., exposed subjects to 0.35 ppm ozone for 130 minutes with exercise and reported a decreased macrophage population but increased neutrophils with significant increases in fibrinogen and albumin in post-exposure lavage fluid, while Devlin, et al.,24 exposed non-smoking male subjects to as little as 80 ppb to 100 ppb ozone for 6.6 hours with moderate exercise and extracted BAL fluid after 18 hours post exposure. They reported significant increases in PMNs, protein, prostaglandin E2, fibronectin, interleukin-6 (IL-6), and lactate dehydrogenase and concluded that exposure to as little as 100 ppb ozone results in inflammation and damage to the alveolar region of the lung.

Still other studies address pulmonary function in response to ozone. Volunteer cyclists were exposed to ozone at concentrations ranging from 0.08 ppm to 0.32 ppm for one hour, and decrements in FEV1 were noted at 0.16 and above in a dose-dependent manner. Older men and women exposed for two hours to 0.45 ppm ozone with alternative period of exercise demonstrated decrements in FVC, FEV1, and FEV3, while Folinsbee, et al., exposed ten non-smoking males to 0.12 ppm ozone for 6.6 hours resulting in decrements in FEV1 and FVC with increases in cough and pain on deep inspiration and indications of hyperreactive airways. The US EPA document on air quality criteria for ozone10 contains a summary table relating pulmonary function deficits to ambient ozone concentrations at 40 ppb and below.

Other investigations also have produced decreases in lung function and increases in airway activity. Folinsbee & Horvath29 exposed subjects to 0.25 ppm ozone in repeated doses separated by 12, 24, 48, and 72 hours and found hyperresponsiveness based on measurement of FEV1. Other studies have shown that 2-hour exposures of greater than 120 ppb produced significant deficits in flows, tidal volume, FVC, FEV1, and specific airway resistance with symptoms of cough, pain on deep inspiration, shortness of breath, throat irritation, and wheezing with longer exposure periods producing more severe effects. Exposed subjects to 0.25 ppm ozone for three hours and noted airway hyperresponsiveness. Increased responsiveness to bronchoconstrictor challenge in asthmatic patients is thought to result from a combination of structural and physiological factors that include increased inner-wall thickness, increases in smooth muscle responsiveness, and mucus secretion as well as genetically modulated innate airway responsiveness. Many report pulmonary function deficits or increases in hyperreactivity at ozone levels of 80 ppb. There are many other studies relating to the effects of ozone on healthy human subjects, but a comprehensive review of this vast body of literature is beyond the scope of this report. The US EPA10 has summarized much of this work in its document on air quality criteria for ozone10 . There are, however, a number of publications suggesting a causal link between long-term ozone exposure and onset of asthma in exposed individuals.

In This Section

Causation Reports

Toxicology Notes and Literature

Toxicology Litigation Support