Differences in the haemorrhagic toxicity of aspirin between rats and mice.

Rats and mice were fed a diet containing aspirin at levels of 0, 0.3, 0.6 and 1.2% for 1 and 4 weeks. Haemorrhagic death and/or haemorrhagic anaemia occurred in rats in a dose-dependent manner. Prothrombin and kaolin-activated partial thromboplastin time indices were also decreased depending on the daily doses. However, no conspicuous haemorrhagic signs were found in mice given aspirin. These results suggest marked differences in haemorrhagic effects of aspirin between rats and mice. From results of supplementary experiments with two metabolites of aspirin, salicylic acid and gentisic acid, and from the fact of close relationship between hepatic concentration of salicylic acid and haemorrhagic effects of aspirin, it is inferred that salicylic acid may be a precursor for the active metabolite(s) to cause haemorrhage. The mechanism of species differences of aspirin is discussed.