Failure to observe pathology in the rat following chronic dosing with acetaminophen and acetylsalicylic acid.

Male Wistar rats were dosed daily by gavage for 200 days with either (1) aspirin, 200 mg/kg; (2) acetaminophen, 200 mg/kg; (3) aspirin and acetaminophen, 200 mg/kg of each; (4) aspirin and acetaminophen, 100 mg/kg of each or (5) vehicle alone. None of the treatments produced any marked signs of toxicity and no drug related deaths were observed. The full dose combination (3) did significantly reduce the weight compared to the control group (5). When urinary lactic dehydrogenase and alkaline phosphatase were measured, all treatments caused some increase in activity but those containing aspirin had the greatest effect. Urinary pH and osmolarity were not effected by the treatments. Complete pathological examination of the animals failed to detect any significant changes when compared to the controls. It is concluded that there is no evidence of a toxic interaction between aspirin and acetaminophen in the rat.