The carcinogenicity of
N-nitrosomethyl-(2-hydroxyethyl)amine (
NMHEA),
N-nitrosomethyl-(3-hydroxypropyl)amine (
NMHPA), and the
p-toluenesulfonate (tosylate)
ester of
NMHEA (
NMHEATs) was tested in male and female F344 rats. The chemicals (25.6 mumol per application) were administered by twice-weekly gavage in
corn oil (0.2 ml) for the lifetime of the animals.
NMHEA was found to be an effective
carcinogen under those conditions. The median survival time for the females was 9 mo
after treatment was initiated, while for the males it was 12 mo. The principal cause of death of the females was
hepatocellular carcinoma (14 of 20), while only 6 of 20 male rats exhibited that
tumor. A few of the male rats had
squamous cell carcinomas of the nasal epithelium (4 of 20),
tumors which were not observed in the females.
NMHPA was a much weaker
carcinogen. Many of these rats survived for 2 yr and most had many age-related
cancers. Nevertheless, 10 of the
NMHPA-treated males and 2 females had
adenocarcinoma of the lung, which was absent in the controls and also induced a significant number of neoplastic nodules in the livers of rats of both sexes.
NMHEATs was also a weak
carcinogen. However, besides many age-related
tumors, it induced some
hepatocellular carcinomas as well as
hemangiosarcomas of the liver.
NMHEATs was at least partially hydrolyzed to
NMHEA, which was detected in the blood plasma of treated rats. A hypothesis has been advanced that
NMHEA is activated to a proximate
carcinogen by
sulfate conjugation of the
hydroxyl group; the present data do not contradict this hypothesis. The relatively lower carcinogenic potency of
NMHPA, the different
tumor spectrum induced by this chemical, and particularly the differences in chemical behavior suggest that its mode of activation is not the same as that for
NMHEA.