Lack of Significant Tumor Induction by Endogenously Formed N-nitrosobis(2 - Hydroxypropyl)amine in Rats Fed Tris(2 - Hydroxypropyl)amine and Sodium Nitrite

The potential for endogenous formation of N-nitrosobis(2-hydroxypropyl)amine (BHP) and car cinogenicity were investigated in male Wistar rats administered tris(2-hydroxypropyl)amine (THPA) mixed in powdered diet at a concentration of 2% and sodium nitrite dissolved in distilled water at concentrations of 0.15% and 0.3% for 102 weeks. Endogenous formation of BHP was demonstrated by its presence in the urine of rats given 2% THPA and 0.3% nitrite, but not in the groups receiving either of these precursors alone. However, significant induction of tumors was not observed in BHP target organs in groups given 2% THPA together with 0.15% or 0.3% nitrite, nor in groups given precursors alone. In BHP non-target organs, various tumors developed in all groups at levels similar to those previously reported for spontaneous lesions in male Wistar rats. The present results indicate that BHP is endogenously formed in rats given 2% THPA and 0.3% nitrite, but that its amount is not high enough for significant induction of tumors in the target organs of BHP in rats. However, since man is exposed to various precursors for the entire lifespan, we can not exclude the possibility that endogenously formed nitrosamines are a potential risk factor in human cancer development. (J Toxicol Pathol 9: 199•`204, 1996)