Effect of exposure to fentanyl aerosol in mice on breathing pattern and respiratory variables.
The breathing pattern of mice that were exposed to fentanyl aerosol was studied (2.7, 5.7, 6.0, 10.0, and 23.6 microg/m(3); for 1 hour), using dimethyl sulfoxide as a vehicle. This study was conducted in a head-only exposure assembly. Body plethysmographs connected to a volumetric pressure transducer were used to capture the respiratory signals, and an on-line computer program capable of recognizing the changes in the breathing pattern was used for monitoring the respiratory pattern. The response of mice to fentanyl exposure was found to be concentration dependent. A lower concentration (2.7 microg/m(3)) showed fast recovery and no mortality, while 100% mortality was observed at a higher concentration (23.6 microg/m(3)). No sensory, pulmonary irritation, and airway limitation in mice was observed, and death occurred probably due to respiratory depression. The concentration that decreased 50% of the respiratory frequency (RD(50)) was estimated to be 6.4 microg/m(3). The extrapolated human threshold limit value, calculated from the RD(50) value, was found to be 0.192 microg/m(3). The concentration that caused 50% mortality in exposed mice (LC(50)) was estimated to be 8.8 microg/m(3). This study shows that aerosolized fentanyl does not cause sensory and pulmonary irritation, and since the RD(50) and LC(50) are very close with a low safety margin, this type of sedative should not be used as an incapacitating agent.
Manral
Laxmi
L
Synthetic Chemistry Division, Defence Research and Development Establishment (DRDE), Gwalior, India. luxmimanral@yahoo.com
Muniappan
Natrajan
N
Gupta
Pradeep K
PK
Ganesan
Kumaran
K
Malhotra
Ramesh Chandra
RC
Vijayaraghavan
Rajagopalan
R
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology*; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D051379:Mice; D023421:Models, Animal; D009294:Narcotics / Q000494:pharmacology*; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology; D012137:Respiratory System / Q000187:drug effects* / Q000503:physiopathology; D020711:Threshold Limit Values
D000336:Aerosols; D009294:Narcotics; D005283:Fentanyl