Thyroid tumors in rats from tetramethylthiourea

Tetramethylthiourea (TMTU) was added to the diet of male and female ChR-CD rats for up to 2 years at levels of 0, 30 and 300 ppm. Fifty rats of each sex were used at each dietary level. High-level males and females and low-level males had a lower body weight and consumed less diet than did the controls. A slight anemia was found in the high-level males and females. Polyuria of a low osmolality was found in high level males and females. Serum thyroxine was lower in high-level males and females than in controls. TMTU-related gross and histologic changes were detected only in the thyroids of high-level males and females. After 3 months on test, the thyroids were enlarged and dark on gross examination. Histologically, there was an increase in follicle lumen size, loss of colloid staining, hypertrophy and hyperplasia of follicular cells, together with hyperemia. These early lesions were diffuse in distribution. Eight (28 percent) of 29 female high level rats, 18 to 24 months on test, developed follicular cell carcinomas with no such tumors in 26 comparable controls (p less than 0.005, Fisher's Exact Test, one tail). Although no metastases were found, capsular and vascular invasion by tumor cells was seen. TMTU was considered to be carcinogenic for the female rat under the conditions of this test.