Lesions in the Larynx of Wistar RccHanTM: WIST Rats

Abstract

Specific regions in the rat larynx exhibit cellular changes in response to inhaled xenobiotics. These regions include the base of the epiglottis, ventral pouch, and medial surfaces of the vocal processes of the arytenoid cartilages. 1 , 2 In order to collect information on the usefulness of trimming techniques, the influence of different vehicles, the impact of different application routes in toxicity studies, and differences between induced vs. spontaneous lesions, the data obtained from a large number of inhalation and non-inhalation studies performed in Wistar RCCHanTM: Wist rats at Harlan Laboratories Ltd Switzerland, all evaluated or reviewed by the same pathologist, were compiled for a detailed review. The value of different trimming techniques was deemed to be greatest for transverse and sagittolongitudinal section techniques, as compared to horizontolongitudinally section techniques. The comparison of lesions encountered in control rats of inhalation studies treated with different vehicles did not reveal differences in the type, distribution pattern, incidence and/or severity of spontaneous lesions. The types of lesions were also independent of different application routes in non-inhalation studies compared to inhalation studies. The pattern of spontaneous lesions in the rodent larynx was determined by degenerative and inflammatory lesions starting most often in the submucosal glands by desiccated secretion followed by mineralization and local inflammation or were induced by impacted foreign bodies. Squamous metaplasia was recorded in the respiratory epithelium overlaying the ventral gland as a spontaneous lesion in male Wistar rats from inhalation studies with a maxim of 20.0% in an inhalation oncogenicity study. Induced metaplastic changes recorded in the larynx were reversible. Other induced lesions in inhalation studies consisted of submucosal edema, necrosis, inflammation and/or granuloma. Induced lesions in non-inhalation studies were found to be exclusively related to reflux laryngitis or food impaction. It is concluded, that in rodents induced lesions of the larynx differ in type, distribution pattern, severity and incidence from spontaneous lesions.

Hyalinization of the Pyloric Stomach in CD-1 Mice Following Oral (Dietary) Administration of the Corticosteroid Agonists Mometasone Furoate, Budesonide, and Flunisolide

“…Positive findings in these tissues/parameters included lymphoid atrophy of the mandibular and mesenteric lymph nodes, spleen, and thymus (Compton and Cidlowski 1986); and a reduction in circulating total leucocytes, predominantly reflecting lower lymphocyte counts and often accompanied by reductions in monocytes, eosinophils, neutrophils, and large unstained cells (data not shown). The molecular mechanisms involved in these changes are not fully understood, though loss of cytokine support and induction of apoptosis are known to be important factors (Chrousos 1995; Schwimmer and Parker 2001; Weber and Iwata 2009; Libretto 1995). Cortical atrophy within the adrenal glands of treated animals was noted at all time points whilst controls were unaffected, as were recovery animals (the finding is assumed to have resolved).…”

Epithelial Alteration Associated With Recovery From Laryngeal Squamous Metaplasia in Rats: Kinetics of Recovery From a Test Item-Related Change

“…1 As a result, rats are often used in inhalation toxicity studies. The upper respiratory tract, particularly the larynx, is a common target organ for many pharmaceuticals, industrial chemicals, agrichemicals, and environmental pollutants 2 –9 and many regulatory risk assessments for potential inhalation exposure to toxicants are based on lesions observed in the upper respiratory tract of rodents. 10…”