LONG TERM TOXICITY STUDY WITH ALCOHOL AND 4‐METHYLPYRAZOLE IN RAT

Abstract

4‐Methylpyrazole, in a dose producing a partial inhibition of the alcohol dehydrogenase activity, was given together with alcohol by peroral administration during 12 weeks in growing rat. The effect of similar doses of alcohol and 4‐methylpyrozole alone were also investigated. Light microscopy of liver, kidney, heart and pancreas revealed no changes related to the administration of 4‐methylpyrazole; furthermore, serum transaminases were normal. The administration of alcohol caused decreased weight gain of the rats; supplementation with 4‐methylpyrazole made this decrease still more pronounced. Fatty change in the livers was conspicuous in rats receiving alcohol alone, and less pronounced after supplementation with 4‐methylpyrazole. There occurred a few cases with a moderate increase in serum creatinin both in rats receiving alcohol and 4‐methylpyrazole, and in those receiving alcohol alone. There were no light microscopic changes in the kidneys of these rats. Although no definite changes related to the treatment demonstrated, it is concluded that further investigations are needed before 4‐methylpyrazole can be used in adequate repeated doses in clinical investigations in man.