Carcinogenicity test of six nitrosamides and a nitrosocyanamide administered orally to rats

yl-N-nltrosobenzamlde (MNB)) and ethylnltrosocyanamlde (ENC) were administered chronically In sodium citrate-buffered drinking water to MRC Wistar rats. ENU Induced tumors of the reticulo-endothelial 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 % Incldenca). HENU produced bone tumors (38 % Incidence) and RES tumors (28% Incidence). ENC produced n.881 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 typhlmurlum TA1535.-JNCI 62: 1523-1528, 1979. Nitrosamides can alkylate cell macromolecules with-out prior metabolic activation, and most previously tested ni trosamides were strongly carcinogenic (l). Nitrosocyanamides are direct alkylating agents (2) and hence might behave biologically like nitrosamides. Even though such compounds are often carcinogenic directly at the site of application, we thought that they might prove to be useful organ-specific carcinogens after oral administration. This paper reports the car-cinogenicity in rats of 6 nitrosamides (including 5 ni-trosoureas) and a nitrosocyanamide (text-fig. I). The nitrosoureas tested were ENU, which served a