3-Cloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a rat thyroid gland carcinogen, does not affect serum levels of TSH and thyroid hormones.

ABSTRACT

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a chlorine disinfection by-product in drinking water, causes follicular adenomas and carcinomas in thyroid glands of Wistar rats with an unknown mechanism. We evaluated effects of MX on blood thyroid stimulating hormone (TSH), thyroxine (T(4)), triiodothyronine (T(3)), prolactin (PRL) and growth hormone (GH) levels in male and female Wistar rats to assess their role in the tumorigenesis. The levels of TSH, PRL and GH in serum of male rats were not significantly affected by a single dose of 1, 10 or 60 mg/kg of MX administered by gavage 2 h before sampling. In repeated dose experiments MX was administered at dose levels of 1, 10 or 60 mg/kg of MX (40 mg/kg for females) in water by gavage daily for 1 or 3 weeks. Thyroid glands, adrenal glands and the liver were evaluated for morphological changes and cell proliferation activity after staining with proliferating cell nuclear antigen (PCNA). The dose of 60 mg/kg MX was toxic upon repeated administration. Nevertheless, MX did not affect blood TSH and T(4) levels at any time point in either sex. T(3) concentration increased transiently in males (by 37% after week 1) at the highest MX dose but not in females. MX did not change the weights of thyroid glands, their morphology and cell proliferation activity by the end of the week 3. MX did not affect blood PRL levels but decreased GH levels in males at all doses after the first week of MX treatment. The results indicate that MX does not alter blood TSH and thyroid hormone levels in rats, and imply that MX may not cause thyroid follicular cell tumors by TSH-mediated hormonal promotion.