Species: Dog Strain/breeder: Beagle Sex: Female Age: 2 years Study type: Chronic toxicity study                    Treatment: i.g., 9 months, cationic amphiphilic compound Animal status: Scheduled death, end of study Clinical findings: Inappetence; weight loss, respiratory distress during the last study weeks Organ: Lung Macroscopic finding(s): All lobes indurated; greyish-yellowish and partly reddish foci up to 1 cm in diameter; marked increase in absolute and relative lung weights Staining: H&E Literature: Jubb KVF, Kennedy PC, Palmer N (1985) Pathology of domestic animals, 3rd edition, volume 2. Academic Press, Inc. San Diego, pp 472-474

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Abstract

9-month i.g. treatment of Beagle dogs with a cationic amphiphilic compound at a dose of 100 mg/kg led to clinical observations of inappetence, weight loss and respiratory distress during the last study weeks.

Necropsy at study termination showed a marked increase in absolute and relative weights of the lungs of all animals and in addition to induration of all lobes multiple greyish-yellowish and partly also reddish foci of up to 1 cm in diameter. Histologic examination revealed marked multifocal granulomatous inflammatory reaction with central accumulation of lipids (vacuoles, cholesterol clefts) and collagen (fibrosis). These lesions are attributed to the cationic amphiphilic properties of the test article. Cationic amphiphilic compounds are known to have a high affinity to lung surfactant and to cause phospholipidosis when administered in high doses and/or over a long period of time. In rodents the pulmonary phospholipidosis is characterised by accumulation of lipid-containing alveolar macrophages (foam cells) and proliferation of pneumocytes type 2. Occasionally a slight concomitant inflammatory reaction can be observed. Long term treatment of dogs with this compound however led to a granulomatous inflammatory reaction around eosinophilic lipid containing deposits and the occurrence of foam cells is much less prominent.