Carcinogenicity of 5-Nitrofurans and Related Compounds With Amino-Heterocyclic Substituents

Summary

Carcinogenicity of eight 5-nitrofurans with heterocyclic substituents at the 2-position of the furan ring was investigated by feeding the chemicals to SpragueDawley female rats. N-[5-(5-nitro-2-furyl)-1,3,4-thiadiazol-2- yl]acetamide induced in 30 rats the highest incidence of tumors with the greatest number of tissues involved: forestomach squamous cell tumors (22), kidney pelvis transitional cell carcinomas (lS), pulmonary alveolar cell carcinomas (16), hemangioendothelialsarcomas (20) of the intestine, mesentery, liver, lung, and pancreas, and a few tumors of other tissues. 2-Amino-5-(5-nitro-2-furyl)-1,3,4- thiadiazole, 2-amino-5-(5-nitro-2-furyl)-1,3,4-oxadiazole, and trans-2-[(dimethylamino)methylimino]-5-[2-(5-nitro- 2-furyl)vinyl]-1,3,4-oxadiazole produced high incidences of mammary tumors. The other four 5-nitrofurans tested: N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamidej 2,2,2trifluoro- N-[4-(5-n itro-2-furyl)-2-thiazolyl]acetamide; 5-(5nitro- 2-furyl)-1,3,4-oxadiazol-2-ol and N-{[3-(5-nitro-2furyl)- l ,2,4-oxadiazol-5-yljmethyl} acetamide were associated with tumor incidences of 40–60%. Two other chemicals were also tested: 2-Amino-5-nitrothiazole caused a low incidence of breast and kidney pelvis tumors, and 2-amino-4-(p-nitrophenyl)thiazole induced a high incidence of breast and salivary gland adenocarcinomas and Iymphomas.