Intratracheal Instillation Methods and the Distribution of Administered Material in the Lung of the Rat

Intratracheal instillation is widely used for respiratory toxicity tests in experimental animals. However, there are wide variations in the techniques used for instillation, and it is thus difficult to compare the results obtained using different techniques. To examine the effect of instillation methods, we compared the distribution of a test substance in the lungs of rats after intratracheal instillations under various conditions. Rats received an intratracheal instillation of 0.3 mL of india ink suspension under different conditions as follows: 3 different angles of body restraint, 0° (supine horizontal), 45° (supine head up) and 90° (vertical head up); 2 instillation speeds, high (40 mL/min) and low (4 mL/min); and 2 different devices, a standard bulb-tipped gavage needle and an aerosolizing microsprayer designed for intratracheal instillation. One hour after treatment under these various conditions, rats were sacrificed, and the local distribution of the suspension in the lungs was observed. No animal restrained in the supine head-up or vertical head-up position died from the treatment; however, fatalities were observed when rats were restrained in the supine horizontal position except under high-speed dosing conditions with a microsprayer. Better distribution of the suspension in the lungs was observed in the rats restrained in the supine head-up position after instillation at high speed when compared with other conditions. These results indicated that high-speed instillation to the subject restrained in the supine head-up position is an appropriate condition for performing intratracheal instillation.