Carcinogenicity Test of Six Nitrosamides and a Nitrosocyanamide Administered Orally to Rats2

Six nitrosamides [ethylnitrosourea (ENU), 2-hydroxyethylnitrosourea (HENU), carboxymethylnitrosourea, 1-nitroso-5,6-dihydrouracil (NDHU), 1-nitrosohydantoin, and N-methyl-N-nitrosobenzamide (MNB)] and ethylnitrosocyanamide (ENC) were administered chronically in sodium citrate-buffered drinking water to MRC Wistar rats. ENU induced tumors of the reticuloendothelial system (RES) (50% incidence), mammary glands, and large intestine. NDHU in drinking water produced hepatocellular carcinomas (96% incidence), but NDHU injected ip caused mostly tumors at the injection sites (54% incidence). HENU produced bone tumors (38% incidence) and RES tumors (28% incidence). ENC produced nasal cavity tumors (36% incidence). Papillomas and/or carcinomas of the forestomach, tongue, and pharynx were induced by most of the compounds, with the highest incidence in the forestomach (47% for MNB); these tumors were attributed to local action when the compounds were ingested. Carcinogenicity was not quantitatively correlated with direct mutagenicity for Salmonella typhimurium TA1535.