Natl Toxicol Program Tech Rep Ser. 2010 Jul(548):1-210.
Ethinyl estradiol is a potent synthetic estrogen that is widely prescribed in oral contraceptives and is also used in the treatment of breast and prostate cancer. Ethinyl estradiol is one of a class of chemicals known as"environmental estrogens" that can affect the hormone activities and possibly reproductive function of wildlife and humans through exposure. The NTP conducted a series of studies on three such chemicals to detect if exposure over the course of multiple generations could have any cumulative effect on animals' reproductive systems or development of cancers. This report describes the results of a set of studies in which rats were exposed to ethinylestradiol for part or all of the study period and examined at the end of two years.
The study consisted of three separate study components; in each, animals were exposed to ethinyl estradiol from the time of conception and through weaning through their mothers, who were given ethinyl estradiol in their feed.In one study we gave feed containing 2, 10, or 50 parts per billion (ppb) of ethinyl estradiol to groups of 50 male and female rats from conception through two years. In the second study, groups of 50 male and female rats were given the same feed concentrations up to 20 weeks following birth, followed by untreated feed for the remainder of the two years. In the third study groups of 50 male and female rats were exposed from conception through weaning, and then given untreated feed for the duration of the study. Control animals received the same feed with no ethinyl estradiol added. Enthinyl estradiol is known to cause cancer at higher dose levels; the concentrations given in this study were below the levels of detection by chemical analysis, to determine the possible effects of trace amounts in the environment. At the end of the study tissues from more than 40 sites were examined for every animal.
In all three study sets effects were seen in the uterus of female rats. The rates of squamous metaplasia increased in females exposed for two years and in females exposed from conception through weaning; endometrial hyperplasia and atypical focal hyperplasia of the uterus also were increased in females exposed for two years. Uterine stromal polyps were increased in female rats exposed from conception through 20 weeks after birth or from conception through weaning. Male rats exposed from conception through weaning had small increases in the rates of preputial gland tumors and three male rats in that study had rare mammary gland adenomas or carcinomas.
We conclude that exposure to trace amounts of ethinyl estradiol during the period from conception through weaning may have been related to development of uterine stromal polyps in female rats and to preputial gland tumors and mammary gland tumors in male rats.
乙炔雌二醇是一种强效合成雌激素，广泛用于口服避孕药，也用于治疗乳腺癌和前列腺癌。乙炔雌二醇是一类被称为“环境雌激素”的化学物质之一，这类物质可通过接触影响野生动物和人类的激素活性，并可能影响其生殖功能。美国国家毒理学计划（NTP）对三种此类化学物质进行了一系列研究，以检测多代暴露是否会对动物的生殖系统或癌症发展产生任何累积影响。本报告描述了一组研究的结果，在这些研究中，大鼠在部分或全部研究期间暴露于乙炔雌二醇，并在两年结束时进行检查。
该研究由三个独立的研究部分组成；在每个部分中，动物从受孕时起，通过其母亲接触乙炔雌二醇，其母亲在饲料中添加了乙炔雌二醇。在一项研究中，我们从受孕到两年，给每组50只雄性和雌性大鼠喂食含有2、10或50十亿分之一（ppb）乙炔雌二醇的饲料。在第二项研究中，每组50只雄性和雌性大鼠在出生后20周内喂食相同浓度的饲料，然后在两年的剩余时间喂食未处理的饲料。在第三项研究中，每组50只雄性和雌性大鼠从受孕到断奶暴露于乙炔雌二醇，然后在研究期间喂食未处理的饲料。对照动物接受相同的饲料，但不添加乙炔雌二醇。已知乙炔雌二醇在较高剂量水平会导致癌症；本研究中给出的浓度低于化学分析的检测水平，以确定环境中痕量物质的可能影响。在研究结束时，对每只动物40多个部位的组织进行了检查。
在所有三个研究组中，均在雌性大鼠的子宫中观察到了影响。暴露两年的雌性大鼠以及从受孕到断奶暴露的雌性大鼠中，鳞状化生率增加；暴露两年的雌性大鼠中，子宫内膜增生和子宫非典型局灶性增生也增加。从受孕到出生后20周或从受孕到断奶暴露的雌性大鼠中，子宫间质息肉增加。从受孕到断奶暴露的雄性大鼠中，包皮腺肿瘤发生率略有增加，该研究中有三只雄性大鼠患有罕见的乳腺腺瘤或癌。
我们得出结论，从受孕到断奶期间暴露于痕量乙炔雌二醇可能与雌性大鼠子宫间质息肉的发生以及雄性大鼠包皮腺肿瘤和乳腺肿瘤的发生有关。
