Reversible pulmonary changes in rats dosed intravenously with imidazoles

Pulmonary changes were studied in Sprague-Dawley-rats dosed intravenously with various dosages around the LD 50 in acute studies, and with 0 (control), 0.001, 0.01 and 0.1 mg/kg b. wt./day St 91-Cl or with 0, 1, 5 and 25 mg/kg b. wt./day St 600-Cl for 4 weeks in subacute studies. Doses of 0.01 mg/kg St 91-Cl and 1 mg/kg St 600-Cl were well tolerated. At higher doses, both compounds caused acute pulmonary congestion, edema and bleeding. The acute changes obviously occurred after each single i.v. injection, and were followed by an intensive hemosiderosis of alveolar macrophages. All findings were reversible. No pulmonary changes were observed in oral subacute studies with both compounds.