A SNOUT-ONLY INHALATION EXPOSURE SYSTEM FOR USE IN RABBIT TERATOLOGY STUDIES

A novel method of snout-only inhalation exposure of rabbits suitable f or the conduct of regulatory inhalation teratology studies is describe d. The system comprises a slightly modified, conventional, rodent expo sure system fitted with specially designed rabbit restraint tubes. The system was validated by exposing groups of pregnant New Zealand White rabbits to metered-dose aerosols of two beta(2)-agonists, salbutamol sulfate and salmeterol xinafoate, for 1 h each day on days 8-20 of pre gnancy. Air and propellant controls and three aerosol concentrations o f compound were used in each experiment. Each group comprised five rab bits. Drug was detected in the plasma of exposed rabbits. Animals acce pted the procedure with ease. Animal losses were low (4%) and consiste nt with mortality experienced with other rodent inhalation exposure sy stems. No adverse clinical signs and only minor effects on maternal bo dy weight gain were observed. No increased incidence of fetal losses o r unexpected fetal abnormalities were detected using this technique co mpared to other routes of administration of these compounds. In contra st to previously described methods of inhalation exposure of rabbits, this technique provides a convenient, effective, and acceptable method of simultaneously exposing large numbers of rabbits whilst retaining the advantages of snout-only rodent systems and avoiding stressful ind ividual dosing methods.