Lifelong exposure to di-(2-ethylhexyl)-phthalate induces tumors in liver and testes of Sprague-Dawley rats
Lifelong exposure to di-(2-ethylhexyl)-phthalate induces tumors in liver and testes of Sprague-Dawley rats
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DOI：
10.1016/j.tox.2004.07.016
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发表时间：
2005-01-31
期刊：
影响因子：
4.5
通讯作者：
Berger, MR
中科院分区：
文献类型：
--
作者：
Voss, C;Zerban, H;Berger, MR
增塑剂邻苯二甲酸二(2-乙基己基)酯(DEHP)是邻苯二甲酸二(2-乙基己基)酯生产、使用和在环境中存在的最重要的物质。在F344大鼠和B6C3F1小鼠的标准致癌实验中，DEHP已被证明可诱发肝细胞肿瘤。此外，DEHP被强烈怀疑是一种发育和生殖毒物。本研究旨在确定低浓度DEHP终身暴露对SD大鼠的长期毒性效应。雄性大鼠730只，分成4组，在饮食的同时给予DEHP，剂量分别为每天300、95、30和0 mg/kg，持续时间长达159周，只有在濒死时才处死。对死亡动物和处死动物的所有器官进行组织病理学检查。每天染毒300 mg/kg DEHP后，睾丸、肝脏和睾丸的肿瘤发生率均显著增加(P=0.04，P=0.05)，并呈剂量相关趋势(P-趋势=0.02，0.03)。肿瘤生存时间分析表明，DEHP诱导的睾丸肿瘤比肝细胞肿瘤发生得更早，而且其多样性随着时间的延长而增加。此外，暴露于最高剂量DEHP的动物显示出显著增加的睾丸小管萎缩率(P<；0.01)。综上所述，本研究首次表明，SD大鼠的睾丸是DEHP致癌的靶器官。这一新发现表明，在评估DEHR潜在的人类健康风险时，评估终身暴露的影响是重要的。此外，应在DEHP毒性靶器官中自发肿瘤发生率较低的大鼠品系中评估其致癌性。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
The plasticizer di-(2-ethylhexyl)-phthalate (DEHP) is the most important phthalate with respect to its production, use and occurrence in the environment. In standard carcinogenicity experiments with F344 rats and B6C3F1 mice, DEHP has been shown to induce hepatocellular tumors. Moreover, DEHP is strongly suspected to be a developmental and reproductive toxicant. The present study aimed at determining the long-term toxic effects of lifetime exposure to low concentrations of DEHP in Sprague-Dawley rat strain. Seven hundred and thirty male rats, stratified into four groups, received DEHP with the diet, resulting in dosages of 300, 95, 30 and 0 mg/kg per day for up to 159 weeks and were only sacrificed when moribund. All organs of the dead and sacrificed animals were histopathologically examined. Significantly increased tumor incidences after exposure to 300 mg/kg per day DEHP (P = 0.04 for testes and 0.05 for liver) and a significant dose-related trend (P-Trend = 0.02 for testes and 0.03 for liver) were detected in both organs liver and testes. Time to tumor analysis revealed that DEHP-induced testicular tumors developed earlier in lifetime than hepatocellular neoplasias, and their multiplicity increased with time. In addition, animals exposed to the highest DEHP dose showed a significantly increased rate of testicular tubular atrophy (P < 0.01). In conclusion, this study shows for the first time that the rat testes are a target organ of DEHP carcinogenicity in Sprague-Dawley rats upon lifetime exposure. This new finding indicates the importance of evaluating the effects of lifetime exposure in assessing the potential human health risks of DEHR In addition, the carcinogenicity should be evaluated in rat strains with low spontaneous tumor incidence in the organs known as target of DEHP toxicity. (C) 2004 Elsevier Ireland Ltd. All rights reserved.