Vehicle control Harlan RCCHan™:WIST rats were examined to provide control data for subsequent studies. The rats (180 male and 180 female) were dosed daily via oral gavage with reverse osmosis water for up to 104 weeks. At necropsy, body weights and macroscopic findings were recorded and tissues were collected for histopathology. The mean body weight at terminal sacrifice was 687 g for males and 466 g for females. The overall survival rate was 62% for males and 59% for females. The most common cause of death for males and females found dead or examined following unscheduled euthanasia was pituitary neoplasia with an incidence of 13.9% for males and 18.9% for females. Macroscopic and neoplastic and nonneoplastic microscopic findings are presented by body system.

This review focuses on the anatomy, histologic preparation, and pathologic evaluation of extraparenchymal bile and pancreatic ducts (BPDs) and their openings at the duodenal papillae in the cynomolgus macaque (Macaca fascicularis), the Beagle dog (Canis familiaris), the Wistar Hanover rat (Rattus norvegicus), and the CD1 mouse (Mus musculus). In nonclinical safety assessment, intraparenchymal BPDs (with sections of liver and pancreas, respectively) are evaluated routinely. However, detailed evaluation of the extraparenchymal BPDs or the duodenal papillae is not included. In the context of nonclinical safety assessment studies, this review describes situations in which evaluation of extraparenchymal ductal structures and duodenal papillae may be useful in characterizing test article-related changes; elucidates anatomic similarities between human, macaque, and dog and notable differences in rats and mice; and consolidates the information required for the histopathologic evaluation of these tissues.

A sporadic, diffuse, interstitial mixed cell epididymitis of unknown etiology was noted in the epididymal cauda and distal corpus of young control Sprague-Dawley (SD) rats. Rats from 2 different suppliers were examined as part of routine toxicology studies. The incidence of this finding was 5/5 (study 1), 2/7 (study 2), and 2/7 (study 3). Although 2 of these studies partially overlapped temporally, none of the affected animals from any study was maintained concurrently with affected animals from any of the other 2 studies, and infectious causes, control article toxicity, or autoimmune processes were considered unlikely etiologies. Inflammation similar to that noted in the epididymides of these young rats was not present in other tissues and was not noted in study cohorts sacrificed at ages older than approximately 11 weeks or in rats of similar age from other concurrent studies. Similar findings were noted sporadically in historical control data, and consequently an age-related finding of unknown etiology and occurring in sporadic clusters is reported in SD rats 11 weeks old.