Distribution, metabolism and excretion of N-nitrosobis(2-hydroxypropyl)amine in Wistar rats

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Abstract
The metabolic fate of the carcinogen N-nitrosobis(2-hydroxypropyl)amine (BHP) in male Wistar rats was studied. The blood level of [1- 14 C]BHP after a single intraperitoneal injection, administered at a carcinogenic dose of 3 g/kg body weight, reached a maximum within 1 h. Whereas a relatively high concentration of 14 C was found in the blood and target organs, such as the lung, liver, thyroid gland and kidney 1 h after the treatment, most of the radioactive labelling had disappeared from the tissues by 24 h after injection. Most of the administered 14 C was eliminated via the urine; 90.8% was excreted in the urine within the 24 h period, 5.5% in the feces and 3.2% by way of expired air. Studies in rats with exteriorized bile flow demonstrated that about 11% of the intraperitoneally administered 14 C was excreted via the bile in 24 h. Analysis by h.p.l.c. detected BHP (78.1% of the dose), HPOP (1.5%), glucuronides of BHP (4.3%) and HPOP (0.16%), MHP (0.03%) and unknown metabolites (6.0%) in the urine 24 h after the treatment. Besides these metabolites, BOP and two unidentified metabolites were also detected in the blood, lung, liver or kidney of rats 3 h after the treatment. These results suggest the involvement of BHP metabolites, HPOP, MHP and BOP, in carcinogenesis and in particular lung carcinogenesis induced by BHP in rats.