A method for comparison of animal and human alveolar dose and toxic effect of inhaled ozone.
Present models for predicting the pulmonary toxicity of O3 in humans from the toxic effects observed in animals rely on dosimetric measurements of O3 mass balance and species comparisons of mechanisms that protect tissue against O3. The goal of the study described was to identify a method to directly compare O3 dose and effect in animals and humans using bronchoalveolar lavage fluid markers. The feasibility of estimating O3 dose to alveoli of animals and humans was demonstrated through assay of reaction products of 18O-labeled O3 in lung surfactant and macrophage pellets of rabbits. The feasibility of using lung lavage fluid protein measurements to quantify the O3 toxic response in humans was demonstrated by the finding of significantly increased lung lavage protein in 10 subjects exposed to 0.4 ppm O3 for 2 h with intermittent periods of heavy exercise. The validity of using the lavage protein marker to quantify the response in animals has already been established. The positive results obtained in both the 18O3 and the lavage protein studies reported here suggest that it should be possible to obtain a direct comparison of both alveolar dose and toxic effect of O3 to alveoli of animals or humans.
Hatch
G E
GE
Environmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Koren
H
H
Aissa
M
M
D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008722:Methods; D010126:Ozone / Q000008:administration & dosage / Q000009:adverse effects* / Q000633:toxicity; D011817:Rabbits
D015415:Biomarkers; D010126:Ozone