Respiratory Tract Effects of Repeated Exposures to Isoprene/ozone Reaction Products in Mice

Upper airway irritation and airflow limitation have been reported in mice during single exposures to the oxidation products (OPs) of isoprene, a hemiterpene emitted by humans and vegetation. This study evaluated the respiratory effects of repeated exposures to isoprene OPs. Male mice of 6 strains were exposed to a reaction mixture comprised of 3227 ± 157 ppm isoprene and 1080 ± 155 ppm ozone 3 hours/day for 4 consecutive days, and respiratory parameters were monitored via head-out plethysmography. Endpoints evaluated were sensory irritation, pulmonary irritation, airflow limitation, and airway responsiveness. Marked enhancement of the sensory irritation and airflow limitation effects was observed with repeated exposures, and pulmonary irritation developed in several strains. A reduction in airway responsiveness occurred in most strains, which may reflect airway mucous hypersecretion. The cumulative effects observed with repeated OP exposures have important implications for non-industrial indoor environments in which exposure may occur over many years. INDEX TERMS Terpene oxidation products, Irritation, Airflow limitation, Repeated exposures, Airway responsiveness INTRODUCTION The reaction products of ozone and terpenes (eg. α-pinene, d-limonene, isoprene) have been shown to cause sensory irritation and airflow limitation during acute 30and 60-minute exposures (Wolkoff et al., 2000; Clausen et al., 2001; Wilkins et al., 2001; Rohr et al., 2002a). Identified stable reaction products and residual reactants could not account for the effects observed, suggesting that irritants were formed that were not identified or measured. In general, terpene oxidation products (OPs) are comprised of a number of higher molecular weight acids, aldehydes, and ketones (Grosjean et al., 1998; Caligorou et al., 1999), as well as a number of radical species, including the hydroxyl radical (Atkinson et al., 1992). Ultrafine particles (diameter <0.1 μm) are also formed through nucleation and/or condensation of low vapor pressure products; such formation has been described in a number of settings (Weschler and Shields, 1999; Long et al., 2000; Rohr et al., 2002b). In previous studies, single, acute 30or 60-minute exposures were evaluated, and only irritation and airflow limitation effects were evaluated. The work reported here focused on isoprene, a human and plant bioeffluent, as isoprene OPs induced the largest effects in other studies. We evaluated the effect of longer (3-hour) exposures to isoprene OPs on nonspecific airway hyperresponsiveness (AHR), sensory irritation, pulmonary irritation, and airflow * Contact author email: [email protected] Proceedings: Indoor Air 2002