The rabbit is occasionally used for inhalation and intranasal safety assessment studies, but there are no detailed descriptions of the anatomy or histology of the rabbit nose. To address this deficit, the nasal cavities of thirty-two control adult rabbits were sectioned and examined to provide mapping of the main epithelial types and histological structures present within the cavity and turbinates. Four levels of the nasal cavity were prepared and examined using anatomic landmarks. Level I was sectioned immediately posterior to the incisors, Level II at the first palatal ridge, Level III immediately anterior to the first upper premolar teeth, and Level IV immediately anterior to the first upper molar. Level I was lined predominantly by squamous epithelium with small amounts of thick transitional epithelium, and examination is recommended only for studies involving test article administration via instillation. Level II was lined primarily with transitional and respiratory epithelia, whereas Levels III and IV were lined with respiratory and olfactory epithelia and often contained nasal-associated lymphoid tissue. The vomeronasal organs were evident only in Level II. The similarities and differences of these features are compared with those of other common laboratory species (rat, mouse, dog, and cynomolgus monkey) and man.
The efferent ducts represent an important site of toxicity in the male reproductive tract but are not routinely examined in toxicity studies. This article describes a primary efferent duct toxicity that resulted in secondary testicular changes in rats. Male rats were administered LTI-1, a leukotriene A₄ hydrolase inhibitor, at doses up to 250 mg/kg/d for 3 month or 150 mg/kg/d for 6 month. At the highest dose levels, testicular changes were predominantly unilateral and characterized by diffuse dilation or atrophy of the seminiferous tubules. These testicular changes correlated with granulomatous inflammation in the corresponding efferent ducts, suggesting that the mechanism for the testicular changes involves obstruction and impaired fluid reabsorption in the efferent ducts. Subsequent buildup in fluid volume and back-pressure upstream of the blockage cause dilation of the seminiferous tubules, which, in its late stages, progress to tubular atrophy. There are important differences in efferent duct anatomy between rats and larger mammals, including humans, such that the latter are less susceptible to testicular injury by this mechanism. Because of the limited relevance of this rat-specific finding to humans, it is important to distinguish testicular changes secondary to efferent duct toxicity from primary drug-induced testicular toxicity.
The use of miniature swine as a nonrodent species in safety assessment has continued to expand for over a decade, and they are becoming routinely used in toxicology and in pharmacology as well as a model for human diseases. Miniature swine models are regularly used for regulatory toxicity studies designed to assess safety of new therapeutic compounds given through different routes of exposure and are used as an alternative model to the canine or the nonhuman primate. Translational preclinical swine study data presented support the current finding that miniature swine are the animal model of choice for assessment of drug absorption, tolerance, and systemic toxicity following systemic exposures. Because research investigators need to be familiar with important anatomic and histopathologic features of the miniature swine in order to place toxicopathologic findings in their proper perspective, clinical and anatomic pathology data from a large number of Sinclair, Hanford, Yucatan, and Gö ttingen breeds from control groups from a wide variety of studies performed between 2004 and 2014 will be presented, compared, and partially illustrated.
Abstract. This article reports 5 cases of oviduct adenocarcinoma in adult captive snakes from Smithsonian's National Zoological Park. This neoplasm was found in 1 of each of the following species: emerald tree boa (Corallus caninus), Amazonian tree boa (Corallus enydris enydris), Burmese rock python (Python molurus bivittatus), Northern pine snake (Pituophis melanoleucus melanoleucus), and corn snake (Elaphe guttata). Grossly, tan to red firm masses were found within oviducts in 3 cases. In an additional 2 cases, the primary tumor was detected only histologically. Microscopically, neoplasms were papillary, and often extended transmurally. The neoplastic cells were polygonal and organized in acini or cords, with often abundant fibrovascular stroma. Hemorrhages and necrosis were present in all cases. Inflammation, myxomatous material, desmoplasia, and bacteria were often observed. Histologic evidence of metastasis was present in all cases. Solid metastases were seen in all animals except the Northern pine snake and involved several organs including the liver, lung, and heart. Emboli of neoplastic cells were observed in all animals but the Burmese rock python and corn snake.
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