Studies of the tumorigenic potential of 4-substituted phenylhydrazines by the subcutaneous route.

4-Methylphenylhydrazine hydrochloride (4-MPH) was administered to randomly bred Swiss mice as 26 weekly sc injections of 140 microgram per gram of body weight and N'-acetyl-4-(hydroxymethyl)phenylhydrazine (AMPH) as 26 weekly sc injections of 500 microgram/g. As a solvent control, physiological saline was also given as 26 weekly sc injections of 0.01 ml/g. The 4-MPH treatment induced a significant incidence (24%) of fibrosarcomas in males. In the 4-MPH-treated females and some AMPH-treated male mice, a few soft-tissue tumors were observed; however, their appearance could not be related to treatment. 4-MPH is formed under special experimental conditions from 4-hydroxymethylphenyl-hydrazine, which is an in vitro breakdown product of agaritine, an ingredient of the cultivated mushroom Agaricus bisporus. The implications of the findings are discussed.