Effect of exposure to fentanyl aerosol in mice on breathing pattern and respiratory variables

Abstract

The breathing pattern of mice that were exposed to fentanyl aerosol was studied (2.7, 5.7, 6.0, 10.0, and 23.6 μg/m³; 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 μg/m³) showed fast recovery and no mortality, while 100% mortality was observed at a higher concentration (23.6 μg/m³). 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 (RD₅₀) was estimated to be 6.4 μg/m³. The extrapolated human threshold limit value, calculated from the RD₅₀ value, was found to be 0.192 μg/m³. The concentration that caused 50% mortality in exposed mice (LC₅₀) was estimated to be 8.8 μg/m³. This study shows that aerosolized fentanyl does not cause sensory and pulmonary irritation, and since the RD₅₀ and LC₅₀ are very close with a low safety margin, this type of sedative should not be used as an incapacitating agent.

Keywords::

• Fentanyl
• aerosol
• RD50
• LC50
• TLV
• mice

Acknowledgments

The authors are thankful to Dr Pravin Kumar for helping in the determination of particle size; Mr. M. Stalin for making inhalation assembly; Mr. A. P. Bansod for the drawings; and are also grateful to Dr S.J.S. Flora for helpful discussions regarding this work.

Declaration of interest: The authors report no financial conflicts of interest. The authors alone are responsible for the content and writing of this paper.