抄録
To minimize concurrent dermal or oral ingestion of test article, nose-only inhalation exposure is now routinely used in inhalation laboratories. However, this exposure procedure requires the restraint of rodents, for periods of up to four hours (accepted maximum).
Pulmonary pharmaceutical products (surfactants for fetal atelectasis or mucolytic medications for cystic-fibrosis, for example) may be administered to humans at high volumes or for long periods of time.
Non-clinical testing to support the human use of these products must also reach high dosages to provide sufficient safety margins.
Calculation of a Maximum Feasible Dose requires: the respiratory minute volume (RMV) - a measured
or calculated value fixed by the body weight of the rat; the chamber concentration of active ingredient - limited by the fixed formulation concentration; and efficient atmosphere generation - optimized during
technical trials. When testing benign pulmonary drugs, the normal four hour exposure must be increased.
At CiToxLAB Hungary, exposures of up to eight hours each day have been used on subacute studies. However, it is critical to ensure that the potential stress of spending 33% of each 24 hour period within restraint tubes does not adversely impact the health status of the animals and compromise the study. We have compared various parameters for control animals restrained for the regular four hours per day with those from animals restrained for the eight hour period each day. There were no significant differences in bodyweight gain, food consumption or microscopic findings that could be ascribed to this prolonged period of restraint.
