Time-course comparison of pulmonary responses induced by intratracheal instillation of administering different vehicles in Crl:CD(ICR) mice

<p>[Aim] Recently, advances in drug discovery technologies have led to the development of the various novel modality drugs, and the inhalation route has attracted attention as a delivery route for novel modalities (Hall et al. Toxicol Pathol., 2021). The safety evaluation of drugs by the inhalation route requires large-scale facilities and a lot of test substance. Under the inhalation route, 20% of the drug reaches at lower respiratory tract and an exposure to lungs is a problematic issue. We have established intratracheal instillation (IT) method and reported its usefulness. At this time we examined the effects on the lung by a single IT of 6 vehicles in mice. [Method] In this study, water for injection, saline, 10% maltose solution, 0.1% Tween 80, 10% PEG400, and 10% DMSO were selected as vehicles. 7-week-old male ICR mice received a single IT of each vehicle of 100 uL/body After administration, general condition and body weight were monitored, and 5 animals from each group were necropsied on 1, 3, 7 and 14 days after administration, and clinical biochemistry, bronchoalveolar lavage fluid (BALF) test, and histopathological examination were performed. [Results] No deaths were observed in all groups throughout the experimental period. In the general condition, all mice showed a transient crepitation after the IT. No vehicle treatment changes were observed in body weight and clinical biochemistry. In the presentation, we also report the results of BALF test, lung weights and histopathology.</p>