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Abstract：
A 28-day repeated oral dose toxicity study of nonylphenol (NP) was performed for an international validation of the \'Enhanced OECD Test Guideline 407\' paying particular attention to the sensitivity of individual endocrine-related parameters. Sprague-Dawley rats, each group consisting of ten males and ten females, were administered NP once daily by gavage at doses of 0 (control), 10, 50, or 250 mg/kg body weight. At 250 mg/kg, three females died or became moribund during the experiment. At this dose, hepatic and renal toxicity was evident in both sexes with increase of relative liver and kidney weights as well as histopathological changes, such as centrilobular liver cell hypertrophy and a variety of renal tubular lesions, and alteration of serum biochemical parameters, some of them being evident from 50 mg/kg in females (glucose and inorganic phosphates). Hematologically, development of anemia was evident at 250 mg/kg in both sexes. Regarding endocrine-related effects, increase of thyroid weight in males was detected from 50 mg/kg. At 250 mg/kg, males exhibited reduction of relative weights of the ventral prostate and seminal vesicles, and females developed irregular estrous cyclicity and vaginal mucosal hyperplasia. Although changes in serum hormone levels were detected in both sexes, magnitude of the changes was small to be regarded as a low toxicological significance. In summary, repeated oral doses of NP to rats for 28 days resulted in hepato-renal toxicity from 50 mg/kg and anemia at 250 mg/kg. Effects on the endocrine system were observed from 50 mg/kg, and assessment of weights and histopathology of endocrine-related organs and estrous cyclicity may be valid in a battery for detecting endocrine effects of NP. The no-observed-adverse-effect level of NP was estimated to be 10 mg/kg per day.
摘要：
对壬基酚（NP）进行了为期28天的重复口服剂量毒性研究，以对“增强的OECD测试指南407”进行国际验证，特别注意个体内分泌相关参数的敏感性。Sprague-Dawley老鼠,每组由10名男性和10名女性组成，以0（对照）的剂量每天通过管饲法施用NP，10、50或250mg/kg体重。在250毫克/千克，在实验过程中，三名女性死亡或垂死。在这个剂量下，肝和肾毒性在两种性别中都很明显，肝脏和肾脏的相对重量增加以及组织病理学变化，如小叶中央肝细胞肥大和各种肾小管病变，和血清生化参数的改变，其中一些是明显的从50毫克/公斤的女性（葡萄糖和无机磷酸盐）。血液学,男女在250mg/kg时，贫血的发展明显。关于内分泌相关的影响，男性甲状腺重量从50mg/kg增加。在250毫克/千克，男性表现出腹侧前列腺和精囊的相对重量减少，女性出现不规则的发情周期和阴道粘膜增生。尽管在男女中均检测到血清激素水平的变化，变化的幅度很小，被认为是低毒理学意义。总之,对大鼠重复口服NP28天导致50mg/kg的肝肾毒性和250mg/kg的贫血。从50mg/kg观察到对内分泌系统的影响，评估内分泌相关器官的重量和组织病理学以及发情周期可能在检测NP的内分泌作用中有效。NP的未观察到的不良反应水平估计为每天10mg/kg。
