Am. J. Respir. Crit. Care Med.,
Volume 156, Number 5, November 1997, 1405-1412
In Vivo Salicylate Hydroxylation: A Potential
Biomarker for Assessing Acute Ozone
Exposure and Effects in Humans
LING
LIU,
JUDITH A.
LEECH,
R. BRUCE
URCH,
and
FRANCES S.
SILVERMAN
Air Quality Health Effects Research Section, Environmental and Occupational Toxicology Division, Environmental Health Directorate,
Health Canada, Ottawa; and Gage Occupational and Environmental Health Unit, University of Toronto, Toronto, Ontario, Canada
Ozone is known to yield hydroxyl radical, which may contribute to ozone-mediated lung injury. In
the presence of hydroxyl radical, salicylate is hydroxylated to form 2,3-dihydroxybenzoic acid (2,3-DHBA). There is no evidence of enzymatic formation of 2,3-DHBA. We hypothesized that salicylate
hydroxylation might be used as a biomarker indicating human exposure to ozone. Healthy, nonsmoking volunteers, 18 to 34 yr of age, were given acetylsalicylic acid (975 mg) or placebo orally 0.5 h
before an exposure. Subjects were exposed to ozone (0.12 or 0.4 ppm) or filtered air in an environmental chamber for 2 h, while performing intermittent exercise. Results indicate significant decrements in FVC, FEV1.0, forced expiratory flows at 50% and 75% of FVC, and peak expiratory flow rate, and an increase in airway resistance, after exposure to 0.4 ppm ozone in comparison with air
control (p < 0.05). Exposure to 0.4 ppm ozone also resulted in increased symptom numbers and severity (p < 0.05). When subjects were exposed to 0.12 ppm ozone, changes of pulmonary function
and symptoms reported were minimal. Plasma concentration of 2,3-DHBA was significantly increased
after exposure to 0.12 and 0.4 ppm ozone in comparison with air control (p < 0.05). There was a significant correlation between ozone-induced changes of pulmonary function and normalized salicylate
hydroxylation (p < 0.05). The results indicate that exposure to ozone can initiate in vivo production
of hydroxyl radical, a potent reactive agent. Salicylate hydroxylation may then serve as a sensitive dosimetric biomarker for ozone exposure, even at subclinical ozone exposure levels.
