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

A chronic toxicity test of 10% nitroglycerin (NT-1 ointment) was carried out in male NZW rabbits. NT-1 ointment was applied to the back skin for 26 weeks at daily doses of 15, 60 and 240 mg/kg as nitroglycerin itself, and 5-week withdrawal period was followed. 1. Topical dermal responses to NT-1 : Macroscopically, erythema, edema, scales, papu1es and dermal thickening were observed in response to NT-1 ointment. In the withdrawal period, however, all of them disappeared. Histopathologically, thickening of epidermis and cell infiltration were observed in response to NT-1 ointment. In addition, elongation of rete ridges and Touton giant cells were found only in 60 and 240 mg/kg groups, and hyperkeratosis only in 240 mg/kg group. At the end of withdrawal period, Touton giant cells were still found in 60 and 240 mg/kg groups, although the other dermal reactions disappeared. 2. Systemic responses to NT-1 ointment: A slight increase in the excretion of loose or mucous feces was observed in 240 mg/kg :group. The weights of right and left kidneys were increased by the administration of 240 mg/kg NT-1 ointment, and a similar trend was seen also in the weight of heart, although there found no such among-group differences at the end of withdrawal period. White blood cells, especially neurtophils, and γ-globulin fraction were increased in response to 240 mg/kg NT- 1 ointment. 3. In conclusion, a no-toxic effect dose of NT-1 ointment as nitroglycerin itself was considered to be 15 mg/kg/day for the skin and 60 mg/kg/day for the general somatic system.