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Mentions: Inflammatory lesions recorded in an acute study (acute study T3) ranged from focal or multifocal dilation of submucosal glands mainly at levels 2 and 3 (Fig. 10), submucosal edema with scattered inflammatory cells, mainly granulocytes and plasma cells (Fig. 11) and/or submucosal subacute inflammation in levels 2, 3 and 6 (Fig. 12). In the acute to subacute phase of inflammation the loss of cilia on the respiratory epithelium took place (Fig. 13). In this study, squamous metaplasia with hyperplasia and keratinization was recorded at the arytenoids projections at level 3 (Fig. 14). In two studies, focal erosions of the epithelium (4-week study T6) or necrosis (4-week study T7) of large portions of the lining epithelium (Fig. 15 , 16) without preference of an epithelial type were present. In the first study, the erosions were observed in single animals of both sexes only at the high dose group at level 6, whereas squamous metaplasia was recorded in a high percentage of the mid and high dose animals at level 6. In a single case, squamous metaplasia was noted at the arytenoid projections at level 3. In the latter study (4-week study T7), subacute inflammation in levels 2, 5 and 6 along with multifocal necrosis in levels 3–6 were accompanied by multifocal squamous metaplasia (Fig. 17) and regenerative hyperplasia at levels 4–6, i.e. induced squamous epithelial changes were noted as a consequence of inflammatory lesions (necrosis, submucosal inflammation).
Lesions in the Larynx of Wistar RccHanTM: WIST Rats
Bottom Line: The types of lesions were also independent of different application routes in non-inhalation studies compared to inhalation studies.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.
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 RCCHan(TM): 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.