a School of Pharmacy , Pusan National University , Busan , Republic of Korea.
b Division of Toxicology, School of Pharmacy , Sungkyunkwan University , Suwon , Republic of Korea.
J Toxicol Environ Health A. 2018;81(11):421-431. doi: 10.1080/15287394.2018.1451188. Epub 2018 Mar 20.
Triclosan (TCS), a common antimicrobial ingredient, is present in many consumer products, including soaps, shampoos, and toothpaste. Owing to its widespread use, potential adverse effects on animals and humans may arise from lifetime exposure, but data on chronic prepubertal exposure of TCS are still lacking. The aim of the present study was to investigate the influence of subchronic TCS exposure (0.25, 25, 250, or 750 mg/kg) on target organ toxicity in prepubertal male rats. After daily administration of TCS to rats by oral gavage for 60 d, a significant reduction in body weight and relative weights of liver, kidneys, testes, and adrenal glands was observed in the 750-mg/kg (high dose) group. Serum alanine aminotransferase and aspartate aminotransferase activities as well as levels of blood urea nitrogen, and creatinine were significantly increased at 750 mg/kg TCS. Further, TCS (750 mg/kg) elevated the protein expressions of hepatic CYP2B1, RXR/PPAR, and levels of malondialdehyde. High-dose TCS exposure induced histological changes as evidenced by reduction of Bowman's space, occlusion of the tubular lumen, and degeneration of tubular epithelial cells in the kidney. Tubular necrosis was confirmed as evidenced by a rise in expression of high mobility group box 1 renal protein. Daily sperm production was significantly diminished by high doses of TCS with marked inhibition of androgen receptor protein expression. Our results indicated that subchronic exposure to excessively high concentrations of 750 mg/kg TCS induced hepatorenal and reproductive toxicities in prepubertal male rats; however, the biological relevance of these findings is questionable as these drug levels are not encountered in the environment.
三氯生（TCS）是一种常见的抗菌成分，存在于许多消费品中，包括肥皂、洗发水和牙膏。由于其广泛使用，动物和人类可能会因终生暴露而产生潜在的不良影响，但关于 TCS 慢性青春期前暴露的数据仍然缺乏。本研究旨在研究亚慢性 TCS 暴露（0.25、25、250 或 750mg/kg）对青春期前雄性大鼠靶器官毒性的影响。经口灌胃给予大鼠 TCS 60 天后，750mg/kg（高剂量）组大鼠体重和肝、肾、睾丸和肾上腺的相对重量显著降低。血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶活性以及血尿素氮和肌酐水平也显著升高。此外，TCS（750mg/kg）升高了肝 CYP2B1、RXR/PPAR 的蛋白表达和丙二醛的水平。高剂量 TCS 暴露引起的组织学变化，如肾小囊空间缩小、管状腔闭塞和管状上皮细胞变性。肾小管坏死被证实为高迁移率族蛋白 1 肾蛋白表达的上升。高剂量 TCS 显著减少了精子的每日产生，并显著抑制了雄激素受体蛋白的表达。我们的结果表明，亚慢性暴露于过高浓度的 750mg/kg TCS 会导致青春期前雄性大鼠的肝肾功能和生殖毒性；然而，由于这些药物水平在环境中并未遇到，这些发现的生物学相关性值得怀疑。
