Airway effects of repeated exposures to ozone-initiated limonene oxidation products as model of indoor air mixtures

► Mice were repeatedly exposed to ozone-initiated limonene oxidation products. ► Sensory irritation is the key effect. ► Repeated exposures did not cause a cumulative effect. ► No airway inflammation was observed. Repeated low-level indoor air exposure to volatile organic compounds (VOCs) may influence the reporting of sensory irritation in the eyes and airways. The ozone-initiated reaction products of limonene, an abundant VOC, were used as a model of indoor air mixtures to study upper airway (sensory) irritation, bronchoconstrictive and alveolar level effects after repeated exposures. Mice were exposed 1h/day for 10 consecutive days to: air, limonene (52ppm/289mg/m3); ozone (0.1ppm/0.2mg/m3); a reaction mixture of limonene (52±8ppm) and ozone (0.5, 2.5 and 3.9ppm) resulting in ∼0.05ppm residual ozone. Neither the limonene nor the ozone exposures alone showed consistent effects on the respiratory parameters. In the limonene/ozone groups, the respiratory rate decreased concentration-dependently with an extrapolated no-effect-level of ∼0.3ppm admixed ozone. Both sensory irritation and airflow limitation were conspicuous effects of the mixtures; sensory irritation appeared rapidly and airflow limitation developed slowly during each exposure. The effects of these parameters did not change with increasing number of exposures. No firm conclusion could be drawn about alveolar level effects. Cells in bronchoalveolar lavage were unchanged irrespective of exposure to air, ozone, and limonene with and without ozone. In conclusion, the study indicated that repeated exposures to ozone-initiated limonene mixtures did not cause sensitization of sensory irritation and airflow limitation. Bronchoalveolar lavage after exposures to ozone, and limonene with and without ozone, respectively, did not show airway inflammation.