Dose-threshold for thyroid tumor-promoting effects of xylazine in rats

To clarify the threshold dose of thyroid tumor-promoting effects of xylazine hydrochloride (XZ), male F344 rats received pulverized basal diet containing 0, 250, 500, or 1000 ppm XZ for 26 weeks with or without initiation of 2400 mg/kg N-bis(2-hydroxypropyl)nitrosamine (DHPN). Thyroid weights significantly increased in the groups with or without DHPN initiation that were given 500 ppm XZ or more. The serum thyroxine (T4) and triiodothyronine (T3) levels decreased significantly in the XZ 250 and XZ 1000 ppm groups, respectively, although there were no remarkable changes in the serum thyroid-stimulating hormone (TSH) levels. Histopathologically, follicular cell hyperplasias and adenomas were induced in the DHPN-alone and DHPN+XZ groups, and the incidences and multiplicities of these lesions in the DHPN groups treated with 500 ppm XZ or more were significantly higher than those in the DHPN alone group. These results suggest that the threshold dose of rat thyroid tumor-promoting effects of XZ is between 250 and 500 ppm under the present experimental condition.