d‐Limonene exposure to humans by inhalation: Uptake, distribution, elimination, and effects on the pulmonary function

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Abstract
The toxicokinetics of d‐limonene were studied in human volunteers exposed by inhalation (2 h, work load 50 W) in an exposure chamber on three different occasions. The exposure concentrations were approximately 10, 225, and 450 mg/m3 d‐limonene. The relative pulmonary uptake was high, approximately 70% of the amount supplied. The blood clearance of d‐limonene observed in this study, 1.1 l kg−1 h−1, indicates that d‐limonene is metabolized readily. About 1% of the total uptake was eliminated unchanged in the expired air after the end of exposure, while approximately 0.003% was eliminated in the urine. A long half‐time in blood was observed in the slow elimination phase, which indicates accumulation in adipose tissues. A decrease in vital capacity was observed after exposure to d‐limonene at a high exposure level. The subjects did not experience any irritative symptoms or symptoms related to the central nervous system (CNS).