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

A novel method of snout-only inhalation exposure of rabbits suitable for the conduct of regulatory inhalation teratology studies is described. The system comprises a slightly modified, conventional, rodent exposure 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 beta2-agonists, salbutamol sulfate and salmeterol xinafoate, for 1 h each day on days 8-20 of pregnancy. Air and propellant controls and three aerosol concentrations of compound were used in each experiment. Each group comprised five rabbits. Drug was detected in the plasma of exposed rabbits. Animals accepted the procedure with ease. Animal losses were low (4%) and consistent with mortality experienced with other rodent inhalation exposure systems. No adverse clinical signs and only minor effects on maternal body weight gain were observed. No increased incidence of fetal losses or unexpected fetal abnormalities were dete...