Natl Toxicol Program Tech Rep Ser. 2010 Aug(547):1-312.
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” which 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 and their offspring were exposed to ethinyl estradiol over the course of four generations.
The continuous-breeding study began with groups of 35 Sprague-Dawley rats of each sex exposed to ethinylestradiol in their feed at concentrations of 2, 10, or 50 parts per billion (ppb). Control animals received the same feed with no ethinyl estradiol added. Animals from the same dose treatment groups were paired and mated, and 25 litters of pups at each exposure concentration (culled to four males and four females each) were continued on study and given feed containing the same concentration of ethinyl estradiol. The process was repeated through a second and third generation, after which the pups were given control feed only, and two more generations were bred in the same manner and given control feed without ethinyl estradiol. Measures of fertility and reproduction were taken for each generation and tissues from the study animals were examined histopathologically.
In all three offspring generations the time to vaginal opening (a measure of onset of puberty) was accelerated in females fed 50 ppb ethinyl estradiol. In the first two offspring generations the estrous cycles of the exposed females were prolonged or aberrant prior to mating. Male rats exposed to ethinyl estradiol had increased rates of mammary gland hyperplasia and mineralization of the kidney tubules.
We conclude that exposure to trace amounts of ethinyl estradiol in the feed showed clear biological activity in male and female rats, including reduced body weights in both sexes, perturbed estrous cycles in females, and induction of mammary gland hyperplasia and kidney tubule mineralization in males.
炔雌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。炔雌醇是一类被称为“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动，并可能影响生殖功能。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，以检测多代接触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，大鼠及其后代在四代过程中接触了炔雌醇。
连续繁殖研究开始时，每组有35只各性别的斯普拉格-道利大鼠，在其饲料中接触浓度为2、10或50十亿分之一（ppb）的炔雌醇。对照动物接受添加了无炔雌醇的相同饲料。来自相同剂量处理组的动物配对并交配，每个接触浓度下的25窝幼崽（每窝挑选出4只雄性和4只雌性）继续进行研究，并给予含有相同浓度炔雌醇的饲料。该过程在第二代和第三代重复进行，之后幼崽只给予对照饲料，又以相同方式繁殖了两代，并给予不含炔雌醇的对照饲料。对每一代进行生育力和繁殖指标的测量，并对研究动物的组织进行组织病理学检查。
在所有三代后代中，喂食50 ppb炔雌醇的雌性大鼠阴道开口时间（青春期开始的一个指标）加快。在前两代后代中，接触的雌性大鼠在交配前发情周期延长或异常。接触炔雌醇的雄性大鼠乳腺增生率和肾小管矿化率增加。
我们得出结论，饲料中接触痕量炔雌醇在雄性和雌性大鼠中显示出明显的生物学活性，包括两性体重减轻、雌性发情周期紊乱以及雄性乳腺增生和肾小管矿化。
