Histopathology of Incidental Findings in Beagles Used in Toxicity Studies

Abstract

The purpose of our publication is to widely communicate the pictures of spontaneous findings occurring in beagles. Spontaneous arteritis occurs commonly in beagles. Frequent sites of arteritis are the heart, spleen, pancreas, epididymis and spinal cord. Morphological similarities between spontaneous and drug-induced arterial lesions may cause confusion when evaluating vascular toxicity of chemicals such as vasodilating agents. Focal and minimal inflammatory lesions are occasionally seen in the lung and may be associated with aspiration of food particles or of unknown causes. A cystic change with copious mucin production occurs occasionally in the mucosal epithelium of the gall bladder. Nesidioblastosis is seen rarely in the pancreas of beagles. C-cell complex and lymphocytic thyroiditis are common thyroid lesions. Spontaneous focal hypospermatogenesis and lobular Sertoli-cell-only seminiferous tubules occurring frequently in beagles must be distinguished from drug-induced damage of the seminiferous tubules in toxicity studies. The morphological differences of the female genital system in each cycle need to be understood; therefore, we present the normal features of the cyclic changes of the female genital organs. Further, we provide more information on spontaneous findings in beagles for exact diagnoses in toxicity studies.

Hyperinsulinaemic, hypoglycaemic syndrome due to acquired nesidioblastosis in a cat

“…5,16 None of these animals had any prior history of clinically significant hypoglycaemia. Vacuolar hyperplasia of islet-cells has also been documented as an incidental finding in diabetic dogs where it is thought to reflect a regenerative response.…”

Spontaneous Pathology and Routine Clinical Pathology Parameters in Aging Beagle Dogs

“…In the adrenal, the focal hyperplasia should not be confused with the accessory adrenal tissue that is occasionally encountered in young Beagles. 28 In a large survey of the spontaneous findings in Beagles aged 8 to 20 months, 12 focal adrenocortical hyperplasia was also described as a sporadic finding. Adrenocortical neoplasia is common in aged dogs, although it is not known whether the focus of cortical hyperplasia noted in the present study may represent a hyperplastic precursor to this.…”

“…As a result, publications detailing the incidence of spontaneous pathology findings in Beagles are confined to animals no older than 2 years. 12,[16][17][18]28 While chronic lifetime studies in Beagle dogs have been undertaken at the Lovelace Respiratory Research Institute (LLRI), 19 published data from these studies does not include detailed observations of the spontaneous pathology noted in dogs aged between 2 and 5 years.AstraZeneca had a cohort of older beagle dogs available for use on routine toxicity studies, with the age of all animals exceeding the upper age limit of Beagles routinely used in toxicity testing (>24 months), raising concerns about a lack of suitable age-and strain-matched historical control data and potential impact on the interpretation of histopathology findings.AstraZeneca has a commitment to fully implement the principles of replacement, reduction, and refinement (3 Rs) for the use of animals in research; therefore, the aim of the study described here was to generate a complete ''guideline compliant'' set of hematology, clinical chemistry, and anatomic pathology end points to support the use of these older dogs in preclinical toxicity testing. For the purposes of this article, we define young adult dogs as being aged between 6 and 24 months and older dogs, between 25 and 37 months.…”

Scientific and Regulatory Policy Committee Points to Consider Review

“…This can be a challenging exercise, even for pathologists experienced in the evaluation of the reproductive tract, due to the small number of animals used and the high variability among individuals. Publications describing testicular development (Picut et al , 2015b, Haruyama et al , 2012, Campion et al , 2013), common spontaneous histologic features of the testes during the process of sexual maturation (Goedken et al , 2008, Rehm, 2000, Sato et al , 2012a, Sato et al , 2012b, Thuilliez et al , 2014), and ovarian development (Picut et al , 2015a, Picut et al , 2014) represent excellent references for this topic.…”