Carcinogenic effects in rats of nitrosopiperazines administered intravesically: possible implications for the use of...

Two nitrosamines derived from nitrosation of piperazine, 1-nitrosopiperazine (NO-PIP) and 1,4-dinitrosopiperazine (DNP), were administered to groups of twelve female F344 rats intravesically. The doses were, respectively, 40 mg and 5.2 mg twice a week for 48 and 36 weeks in aqueous solution. Ten DNP-treated animals survived the treatment; six had tumors related to the treatment, nasal mucosa adenocarcinomas or neuroblastomas in five and a transitional cell carcinoma of the bladder in one. Rats treated with NO-PIP received a ten times greater dose, and all died by week 59, two with transitional cell neoplasms of the bladder and four with carcinomas of the nasal mucosa. NO-PIP was probably in part converted by transnitrosation to DNP. Piperazine, widely used as an oral anti-helminthic, could interact with nitrosating agents in vivo to form the two nitrosamines here shown to pose a possible carcinogenic risk if present in the bladder, by absorption through the bladder wall.