1. Tissue From a Dog 10 mo male Beagle 7-day In-Vivo toleration study Tim LaBranche, DVM, PhD, DACVP Pfizer Global R&D Saint Louis, MO timothy.labranche@pfizer.com Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

10. Summary 1)Overall diffuse, severe decrease in size of lobes. 2)Yet, bronchi are distended and tortuous (bronchiectasis), with variable, occasionally attenuated, airway epithelium. 3)Loss of alveolar profiles. 4)Severely increased interstitial collagen. 5)Type II pneumocyte hypertrophy / hyperplasia. 6)Lymphohistiocytic aggregates. 7)Interlobular septa, pleura, and blood vessels are OK. Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

11. Pulmonary Hypoplasia Compressive forces restricting tissue growth during organogenesis. –Congenital diaphragmatic hernia. –Anasarca. Remaining lung lobes normal in appearance. No genetic history in dog line (commercial supply). Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

12. Questions? Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only