Human reference values for acute airway effects of five common ozone-initiated terpene reaction products in indoor air.

Toxicology letters

PubMedID: 23164675

Wolkoff P, Larsen ST, Hammer M, Kofoed-Sørensen V, Clausen PA, Nielsen GD. Human reference values for acute airway effects of five common ozone-initiated terpene reaction products in indoor air. Toxicol Lett. 2013;216(1):54-64.
Ozone-initiated monoterpene reaction products have been hypothesized to cause eye and airway complaints in office environments and some have been proposed to cause skin irritation and sensitization. The respiratory effects of 60 min exposures to five common oxidation products from abundant terpenoids (e.g. limonene), used as solvent and fragrance in common household products or present in skin lipids (e.g. squalene), were studied in a head out mouse bioassay. This allowed determination of acute upper airway (sensory) irritation, airflow limitation in the conducting airways, and pulmonary irritation in the alveolar region. Derived human reference values (RFs) for sensory irritation were 1.3, 0.16 and 0.3 ppm, respectively, for 4-acetyl-1-methylcyclohexene (4-AMCH), 3-isopropenyl-6-oxo-heptanal (IPOH), and 6-methyl-5-heptene-2-one (6-MHO). Derived RFs for airflow limitation were 0.8, 0.45, 0.03, and 0.5 ppm, respectively, for dihydrocarvone (DHC), 4-AMCH, 4-oxo-pentanal (4-OPA), and 6-MHO. Pulmonary irritation was unobserved as a critical effect. The RFs indicate that the oxidation products would not contribute substantially to sensory irritation in eyes and upper airways in office environments. Reported concentrations in offices of 6-MHO and 4-OPA would not result in airflow limitation. However, based upon the RFs for IPOH and 4-OPA, precautionary actions should be considered that disfavor their formation in excess.