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In female rats the administration of 1,5 mmol/kg of, respectively, propyphenazone and phenazone over a period of 12 weeks produces a histologically detectable fatty degeneration and reactive-inflammatory changes of the liver, presumably caused by reactive metabolites. These slight morphological alterations do not lead to an increase in plasma enzyme activities. Only in case of phenazone administration, reduced increases in body weight are indicative of a toxic effect. The acceleration of hexobarbital degradation and N-demethylation and the increase in liver weight testify to the inductive activity of both these compounds.

After oral application of aminophenazone to animals (170 and 340 mg/kg daily, over up to 17 weeks), the authors investigated the effect of this drug on some liver functions and performed also a morphological study. They found that aminophenazone produces an increase of the smooth ER, peripheral fatty degradation and reactive-inflammatory responses of the liver, the intensity of these phenomena being dependent upon the dose and time of application. The increase of the smooth ER is the expression of the inductive effect which persists throughout the whole experimental period and manifests itself by accelerated degradation of hexobarbital, increased N-demethylation, increased ascorbic acid synthesis and increased liver weight. The increase in body weight is reduced in the animals treated. The enzyme activities in the plasma lie within the range observed with control animals; they are no indicator of the slight live changes stated. Reactive metabolites and/or the impairment of other metabolic reactions may be considered to be the cause of the hepatotoxic effect of aminophenazone.