Idiopathic Aneurysms of the Ascending Aorta in the Mouse and Rat.

Aneurysms of the ascending aorta, unrelated to xenobiotic administration, are described in 5 rats and 2 mice in nonclinical safety studies conducted at Charles River Laboratories (CRL) sites over the past 10 years. The most prominent microscopic finding was focal dilation with disruption of the wall of the ascending aorta with chronic adventitial inflammation or fibroplasia. The pathogenesis of this finding is unknown. There were no associated macroscopic findings, clinical abnormalities, or vascular lesions elsewhere. The results of a search of historical control data from toxicology studies of 1 day to 72 weeks' duration performed at CRL for aortic findings from 5900 mice and 23,662 rats are also reported. Aortic lesions are uncommon in mice and rats used in nonclinical safety studies, but toxicologic pathologists should be aware that aneurysms of the ascending aorta with fibroplasia and inflammation in the aortic wall and adventitia may occur spontaneously or iatrogenically, as they have the potential to impact interpretation in toxicology studies.

Evaluation of Adrenal Cortical Function in Neonatal and Weanling Laboratory Beagle Dogs.

The most common target organ for toxicity in the endocrine system is the adrenal gland, and its function is dependent upon the hypothalamus and pituitary gland. Histopathologic examination of the adrenal glands and pituitary gland is routinely performed in toxicity studies. However, the function of the adrenal gland is not routinely assessed in toxicity studies. Assessment of adrenal cortical function may be necessary to determine whether a histopathologic finding in the adrenal cortex results in a functional effect in the test species. As juvenile toxicity studies are more commonly performed in support of pediatric indications for pharmaceuticals, it is important to establish historical control data for adrenal gland function. In this study, adrenal cortical function was assessed in control neonatal and weanling beagle dogs as part of an ongoing juvenile toxicology program. Measurements of serum adrenocorticotropic hormone (ACTH), cortisol prior to and following administration of exogenous ACTH, and aldosterone were conducted beginning at 2 weeks of age continuing through 26 weeks of age. Serum electrolyte concentrations were determined at 4, 13, and 26 weeks of age. Dogs as young as 2 weeks of age synthesize and secrete adrenal cortical hormones and exhibit a functional hypothalamic pituitary adrenal axis.