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Effects of R-(+)-and S-(-)-limonene on the respiratory tract in mice

K S Hougaard

M Hammer

National Institute of Occupational Health, Lersø Parkalle 105, DK-2100, Copenhagen Ø, Denmark

Y Alarie

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 260 Kappa Drive, Pittsburgh, Pennsylvania 15238

P Wolkoff

P A Clausen

C K Wilkins

G D Nielsen

National Institute of Occupational Health, Lersø Parkalle 105, DK-2100, Copenhagen ø, Denmark

The effects of airborne R-(+)- and S-(-)-limonene were studied in conscious BALB/c mice by continuous monitoring respiratory rate (f), tidal volume (VT) and mid-expiratory flow rate (VD) during an exposure period of 30 min. Both enantiomers decreasedffrom a trigeminal reflex, i.e., due to sensory irritation. The exposure concentration decreasingf by 50% (RD50) in the first 10 min of the exposure period was estimated to be 1076 ppm for R-(+)-limonene and 1467 ppmforS-(-)-limonene. Resultsforsensoryirritation ofR –(+)-limonene in BALB/c mice and humans are in close agreement. The reported sensory irritation threshold is above 80 ppm in humans while the no – observed – effect level was estimated to be 100 ppm in mice. The enantiomers were devoid of pulmonary irritation or general anesthetic effects with R-(+)-limonene <1599 ppm and S-(-)-limonene <2421 ppm. R-(+)-limonene did not influence VT below 629 ppm. S-(-)-limonene increased VT above 1900 ppm. Both enantiomers induced a mild bronchoconstrictive effect above 1000 ppm.

Key Words: sensory irritation • pulmonary irritation • airflow limitation • R-(+)-limonene, S-(-)-limonene, BALB/c mice • inhalation

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