PERCUTANEOUS SUBACUTE TOXICITY STUDY OF 10% NITROGLYCERIN (NT-1 OINTMENT) IN RABBITS

NT-1 ointment is a compound containing 10% nitroglycerin which is topically applied to the skin for angina pectoris. The subacute toxicity of this compound was examined by the continuous application for 5 weeks to the shaven skin of rabbit back at dose levels of 240, 120 and 60 mg/kg, and the recovery was examined 3 weeks after withdrawal of the drug. No special skin response to the NT-1 ointment was observed other than an erythema of the grading 2-3 Draize points, while the control ointment, which was the base ointment without nitroglycerin, showed a higher grade of erythema equivalent to 4 Draize point with crusta formation. No relationship between the dose level of NT-1 ointment and the skin response was observed, and skin response was thought to be caused mainly by the base ointment. The skin response gradually reduced even during the application period, and the skin response disappeared within a few days after withdrawal of the ointment. Histological examination of the treated skin at the respective ends of the application and recovery periods showed thickening of the corneum and epithelial layer, round cell infiltration and fibrosis in the corium, and development of hair folliculi in the subdermis. No systemic effect of the topically applied NT-1 ointment was observed in the majority of the animals, either in behavior, hematologic and electrocardiographic examination, food consumption, body weight change or urinalysis.