Carcinogenicity of N-[4-(5-Nitro-2-furyl)-2-thiazolyl] acetamide in Female Rats

Summary

N-[4-(5-Nitro-2-furyl)-2-thiazolyl] acetamide was fed to 70 female Sprague-Dawley weanling rats at a dosage of 0.199% by weight for 46 weeks, followed by 20 weeks of the control diet. Forty control rats received only ground diet for the entire 66 weeks. Rats were weighed and food consumption was determined biweekly at first and then monthly. With weekly palpation the first mammary tumor was detected at 16 weeks, and tumor incidences are based on the number of rats alive at this time. Every 1 or 2 weeks, 1 rat was sacrificed to determine any early pathological changes of the urinary tract or other internal organs.

Of the 56 rats that survived 16 or more weeks, 52 had tumors with the following organ distribution: 47 mammary tumors (24 fibroadenomas and 23 adenocarcinomas), 6 salivary gland adenocarcinomas, 7 alveolar cell carcinomas of the lung, 2 transitional cell carcinomas of the kidney, 3 skin tumors (squamous cell carcinoma, fibrosarcoma, mastocytoma), 1 small intestinal adenocarcinoma, and 1 splenic lymphosarcoma with hepatic metastases. A systemic lymphoreticular response involving the spleen and lymph nodes was seen in a majority of the rats, and several rats had edema, hemorrhage, and partial destruction of the adrenal gland. No tumors were found in the control rats.

A fibroadenoma, an adenofibroma, and an adenocarcinoma of mammary origin and an adenocarcinoma of salivary gland origin were transplantable to the subcutaneous tissue of female Sprague-Dawley weanling rats with the following incidences of transplantable tumors: 7/24, 4/12, 9/12, and 14/24, respectively. Two of the 9 mammary adenocarcinomas that grew in recipient rats metastasized: one through the abdominal wall and into the liver, the other to the spleen.