Inhalation Toxicity of Aerosolized Pentamidine Isethionate in Rats and Dogs
| Autor: | C. Banks, G. Lulham, I. Bekersky, R. A. Hiles, S. Mong, P. Tellier |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Pathology medicine.medical_specialty Pentamidine Isethionate Physiology Toxicology Rats Sprague-Dawley Dogs Administration Inhalation medicine Animals Respiratory system Lung Pentamidine Aerosols Inhalation business.industry Respiration Respiratory disease Organ Size respiratory system medicine.disease Rats medicine.anatomical_structure Toxicity Female Larynx Nasal Cavity business Respiratory minute volume Respiratory tract |
| Zdroj: | Toxicological Sciences. 23:382-390 |
| ISSN: | 1096-0929 1096-6080 |
| Popis: | The toxicity of inhaled aerosolized pentamidine isethionate solutions in rats and dogs was evaluated. Nose-only exposure equipment and a mass mean aerodynamic particle size of < or = 2 microns were employed. Rats received either a single inhaled dose estimated at 0, 1.4, 2.1, or 6.0 mg/kg/exposure day or 4 inhaled doses evenly spaced over 13 weeks estimated at 0, 0.35, 0.7, or 1.4 mg/kg/exposure day. Dogs were administered a single inhaled dose estimated at 0, 1.1, 3.4, or 5.0 mg/kg/exposure day. Rats administered a single inhaled dose of 6.0 mg/kg/exposure day exhibited respiratory distress. The lung-with-trachea weights of these animals were elevated relative to controls. The histopathology of acutely exposed rats consisted of dose-related neutrophil infiltration in the turbinates, larynx, and bronchi; erosion of epithelium in the turbinates and larynx; thickening of the alveoli walls with alveolar accumulation of mononuclear cells and neutrophils; and rhinitis. Rats in the highest dose group in the subchronic evaluation exhibited decreased body weight gains and reduced lung-with-trachea-to-body weight ratios relative to controls. Hematology, clinical chemistry, and urinalysis values were within normal ranges. Microscopic pulmonary tissue changes were similar to those found in acute exposure with certain lesions (e.g., mucous cell hyperplasia) suggestive of a more chronic process. In addition, lung fibrosis was seen at the highest dose. In dogs, pentamidine isethionate did not cause a change in the respiratory minute volume (not measured in rats). Elevated lung-with-trachea weights were noted in the high- dose females. Hematology, clinical chemistry, and urinalysis values were within normal ranges.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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