Improved oral dosing technique for rats.

Area of Science:

• Toxicology
• Preclinical drug development
• Laboratory animal science

Background:

• Gavage administration in rodents can lead to dyspnea and death, often due to accidental aspiration of the oral dose.
• This issue is not attributed to technical error, as control groups also experienced mortality with similar symptoms.
• Even hypertonic, acidic solutions, when matched for tonicity and pH, caused similar adverse effects, indicating aspiration as the likely cause.

Purpose of the Study:

• To develop a safer gavage dosing method for laboratory rodents.
• To minimize gavage-related deaths and pulmonary symptoms in preclinical safety assessments.
• To identify optimal cannula specifications for effective and safe oral administration.

Main Methods:

• Evaluation of various cannulae (diameters, lengths, materials) to find a safer dosing method.
• Testing of a modified steel cannula (70-mm long, 4-mm tip diameter) for adult rats.
• Adjustment of cannula tip diameter based on rat body weight for optimal dosing.

Main Results:

• The modified dosing cannula virtually eliminated gavage-related deaths in rats.
• The intratracheal lethal dose was significantly lower than the oral LD50, confirming aspiration risk.
• The chosen cannula design allows for economical dosing speeds without causing trauma.

Conclusions:

• Adoption of the modified dosing cannula method can prevent unnecessary deaths in laboratory rodents.
• This technique reduces spurious "treatment-related" pulmonary symptoms observed in preclinical studies.
• The improved gavage method enhances the reliability and ethical conduct of drug safety assessments.