Mechanisms of acute inhalation effects of (+) and (-)-alpha-pinene in BALB/c mice.
The effects of (+)-alpha-pinene and (-)-alpha-pinene vapours were studied for respiratory effects in BALB/c mice. The (+) enantiomer showed persistent sensory irritation effect on the upper respiratory tract during exposures in the range of 100 to 3691 ppm. The threshold concentration for this effect was calculated to be about 70 ppm, which is close to the no-effect level of about 40 ppm in humans. A significant airflow limitation occurred from exposure concentrations of 200 ppm and higher. No irritating effect was observed at the alveolar level and no central nervous system effect was obvious. In the exposure range from 218 to 5213 ppm, the (-) enantiomer produced only a short-lasting sensory irritation effect during the first 10 min. of exposure and only at concentrations above 2900 ppm. The tidal volume decreased significantly from approximately 400 ppm, but it was first conspicuous above 1000 ppm. Airflow limitation appeared consistently from approximately 2000 ppm. The (-) enantiomer also induced anesthesia/and or pulmonary irritation as well as sudden death at concentrations above 2600 ppm. Overall, the enantiomers showed different time-dependent and stereoselective effects. The lower sensory irritation effect of the (-) enantiomer probably being due to less of the molecule being adsorbed to a sensory irritant receptor.
Nielsen
Gunnar Damgård
GD
National Institute of Occupational Health Denmark, Lersø Parkallé 105, DK-2100 Copenhagen O, Denmark. gdn@ami.dk
Larsen
Søren Thor
ST
Hougaard
Karin Sørig
KS
Hammer
Maria
M
Wolkoff
Peder
P
Clausen
Per Axel
PA
Wilkins
Cornelius Kendall
CK
Alarie
Yves
Y
D000280:Administration, Inhalation; D000818:Animals; D000081008:Bicyclic Monoterpenes; D002490:Central Nervous System / Q000187:drug effects; D007509:Irritants / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D039821:Monoterpenes / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D012123:Pulmonary Ventilation / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects*; D013237:Stereoisomerism; D013990:Tidal Volume / Q000187:drug effects
D000081008:Bicyclic Monoterpenes; D007509:Irritants; D039821:Monoterpenes; C005451:alpha-pinene