The effect of repeated intratracheal instillation of different vehicles in Crl:CD(SD) rats

<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 7-day repeated IT instillation of 7 vehicles in rats. </p><p>[Method] In this study, 5% PEG400, 5% DMSO, 0.1% Tween 80, saline, water for injection, McIlvaine buffer (pH 7.0), and PBS were selected as vehicles. 8-week-old male SD rats were received IT of each vehicle of 1 mL/kg for 7days. General condition and body weight were monitored, and 5 animals from each group were necropsied after dosing and recovery. Clinical biochemistry, BALF test, and histopathology were performed.</p><p>[Results] No deaths were observed in all groups throughout the test period. In the general condition, all mice showed a transient crepitation was observed 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>