Eighteen month oral study of aspirin, phenacetin and caffeine, in C57Bl/6 mice.

Groups of 40 male and 40 female C57BL/6 mice were maintained for 75-80 weeks on meal form diets containing aspirin, phenacetin and caffeine either singly or in combination. The maximum daily doses of phenacetin alone and the APC combination were approximately one-half of their previously determined respective oral LD50's. Mild, nonprogressive histopathologic changes of the urinary tract were noted with these changes first evident in animals given the highest dose of phenacetin. Sulfhemoglobinemia was also induced in all groups of animals given phenacetin alone or in combination indicating that toxic doses were administered oral LD50's. Mild, nonprogressive histopathologic changes of the urinary tract were noted with these changes first evident in animals given the highest dose of phenacetin. Sulfhemoglobinemia was also induced in all groups of animals given phenacetin alone or in combination indicating that toxic doses were administered oral LD50's. Mild, nonprogressive histopathologic changes of the urinary tract were noted with these changes first evident in animals given the highest dose of phenacetin. Sulfhemoglobinemia was also induced in all groups of animals given phenacetin alone or in combination indicating that toxic doses were administered. Under the conditions of this study, evidence of carcinogens was not demonstrated for any of the drugs given alone or in combination.