Carcinogenicity of Dipyrone in (C57BL/6 × C3H)F1 Mice2

Abstract

The carcinogenicity of dipyrone (sulpyrin)--[(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4 -yl) methylamino]methanesulfonic acid sodium salt monohydrate--which is widely used as an antipyretic anodyne in Japan and in some European countries, was examined in 314 (C57BL/6 X C3H)F1 mice. Male animals were given 0.5% (group I-a) or 0.125% (group I-b) dipyrone in their drinking water for 78 weeks, and female animals were given 1.0% (group II-a) or 0.25% (group II-b) dipyrone in their drinking water for 78 weeks; both males and females were observed for 86 weeks. Twenty-seven of 48 (56%) group I-a animals and 36 of 44 (82%) group II-a animals developed hepatic tumors, and the tumors in group II-a mice developed earlier than those in the control animals. The tumor incidences were significantly higher than those of 8 of 44 (18%) and 3 of 51 (6%) in the respective control groups. The multiplicity of the hepatic tumors was also significantly increased in groups I-a, I-b, and II-a. Hepatic adenoma incidence was related to the dose of dipyrone in the males. These results show that dipyrone enhances the development of hepatic tumors in mice.