Experimental and Toxicologic Pathology 62 (2010) 163–169 Pubertal exposure to thiodiazole copper inhibits thyroid function in juvenile female rats Le Zhang a , Jie Wang b,Ã , Guo-Nian Zhu a,Ã , Lai Su b a Institute of Pesticide and Environmental Toxicology, Zhejiang University, 268 Kai Xuan Road, Hang Zhou 310029, Zhejiang Province, PR China b Supervision and Test Center for Pesticide Safety Evaluation and Qualiy Control, 8 East Shenliao Road, Tiexi District, Shenyang 110021, Liaoning Province, PR China Received 29 January 2009; accepted 17 March 2009 Abstract Thiodiazole copper, as a thiadiazole fungicide, is widely used in China. The structure of thiodiazole copper shows a close relationship with N,N-methylene-bis (2-amino-1,3,4-thiadiazole) (Bis-A-TDA), which is a teratogen. A few studies have shown that some of the thiadiazole fungicides act as endocrine disruptors via disturbance in thyroid hormone homeostasis. Little is known about the effect of pubertal exposure to thiodiazole copper on the thyroid in pubertal female rats. Based on the protocol of the 20-day Pubertal Female Assay, we attempt to estimate the possible effects of exposure to thiodiazole copper on thyroid hormone and hepatic enzyme activity in female rats. Postnatal days (PND) 22-old Sprague–Dawley rats were administered with thiodiazole copper daily by oral gavage at doses 0, 4, 10, 20 or 30 mg/kg/day for 20 days. After treatments, the rats were sacrificed for blood collection; the reproductive organs, liver, pituitary, adrenal and thyroid gland were harvested. The results indicated that changes in thyroid endpoints following thiodiazole copper administration decreased serum triiodothyronine (T 3 ) and thyroxine (T 4 ) concentrations, increased thyroid stimulating hormone (TSH) concentrations and the weight of thyroid gland, induced hepatic uridine diphosphate glucuronyl transferase (UDPGT) activities in the highest dose group and produced thyroid gland hyperplasia. No histological changes were observed in uterus and ovaries moreover, age and weight at vaginal opening (VO) were unaffected by thiodiazole copper in all treatment groups. The absolute weights of liver and kidney were found to have decreased significantly in female rats. These data and changes demonstrate that thiodiazole copper is likely a thyroid disrupter in female rat following exposure during development, but doesnot have effect on the development of pubertal female rats. Further studies using environmentally relevant doses are needed for hazard identification. r 2009 Elsevier GmbH. All rights reserved. Keywords: Thiodiazole copper; Pubertal development; Thyroid; UDPGT; Rat Introduction Finding novel green compounds with high activity and low toxicity is a development status and trend of future pesticide. Due to the excellent bioactivities of ARTICLE IN PRESS www.elsevier.de/etp 0940-2993/$ - see front matter r 2009 Elsevier GmbH. All rights reserved. doi:10.1016/j.etp.2009.03.005 Ã Corresponding authors. E-mail addresses: wj1890@vip.163.com (J. Wang), zhugn@zju.edu.cn (G.-N. Zhu).