Effects of R-(+)- and S-(-)-limonene on the respiratory tract in mice.
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 decreasedf from a trigeminal reflex, i.e., due to sensory irritation. The exposure concentration decreasing f by 50% (RD50) in the first 10 min of the exposure period was estimated to be 1,076 ppm for R-(+)-limonene and 1,467 ppm for S-(-)-limonene. Results for sensory irritation of R-(+)-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 < or =1,599 ppm and S-(-)-limonene < or =2,421 ppm. R-(+)-limonene did not influence VT below 629 ppm. S-(-)-limonene increased VT above 1,900 ppm. Both enantiomers induced a mild bronchoconstrictive effect above 1,000 ppm.
Larsen
S T
ST
National Institute of Occupational Health, Copenhagen, Denmark.
Hougaard
K S
KS
Hammer
M
M
Alarie
Y
Y
Wolkoff
P
P
Clausen
P A
PA
Wilkins
C K
CK
Nielsen
G D
GD
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D001273:Atmosphere Exposure Chambers; D053138:Cyclohexenes; D006801:Humans; D000077222:Limonene; D008297:Male; D008450:Maximal Midexpiratory Flow Rate / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D019055:No-Observed-Adverse-Effect Level; D012119:Respiration / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects* / Q000503:physiopathology; D012684:Sensory Thresholds; D013237:Stereoisomerism; D013729:Terpenes / Q000008:administration & dosage / Q000633:toxicity*; D013990:Tidal Volume / Q000187:drug effects
D000393:Air Pollutants; D053138:Cyclohexenes; D013729:Terpenes; D000077222:Limonene