DETECTION OF ALDEHYDES IN BRONCHOALVEOLAR LAVAGE OF RATS EXPOSED TO OZONE

We report the detection of hexanal, heptanal, and nonanal in the bronc hoalveolar lavage (BAL) of rats exposed to 0.5 to 10 ppm ozone with or without simultaneous 5% CO2. These three aldehydes primarily result f rom the Criegee ozonation of specific mono- or polyunsaturated fatty a cids that are present in significant amounts in the rat lung; e.g., pa lmitoleic acid gives heptanal, oleic gives nonanal, and linoleic and a rachidonic can give hexanal. Hexanal also is produced in the ozone-ini tiated autoxidation of any n-6 polyunsaturated fatty acid, and thus is a measure of generalized oxidative stress. (Monounsaturated fatty aci ds do not undergo appreciable autoxidation.) This detection and quanti tation of aldehydes directly demonstrates for the first time that unsa turated fatty acids undergo Criegee ozonation in the lung when ozone i s inhaled. Exposure to ozone alone produced smaller apparent yields of the three aldehydes than did exposure to ozone plus 5% CO2. Hexanal, heptanal, and nonanal can be detected in BAL of rats 5 hr after the en d of the ozone exposure, but after more than 5 hr only hexanal can be found, probably from ozone-induced autoxidation of n-6 PUFA that conti nues after ozone exposure. The measured amounts of aldehydes are low, and that, coupled with inherent biovariability, suggests that aldehyde s may not be useful as quantitative dosimeters. However, they can be u seful biomarkers, since some of these aldehydes (e.g., nonanal) are pr oduced in ozone-specific pathways and aldehydes are the most easily de tected among the lipid ozonation products (LOP). Furthermore, our iden tification of these aldehydes by BAL, coupled with our recognition tha t ozone itself cannot penetrate far enough into the lung to cause many of the effects associated with the inhalation of ozone, suggests that these aldehydes, as well as other types of LOP (such as hydroxyhydrop eroxides and Criegee ozonides), may act as signal transduction molecul es, activating lipases and causing the release of inflammatory molecul es by a variety of pathways not yet entirely elucidated. (C) 1996 Soci ety of Toxicology.