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Multiple endocrine disrupting effects in rats perinatally exposed to butylparaben

机译:在围产期接触对羟基苯甲酸丁酯的大鼠中具有多种内分泌干扰作用

摘要

Parabens comprise a group of preservatives commonly added to cosmetics, lotions and other consumer products. Butylparaben has estrogenic and anti-androgenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine sensitive endpoints, however, remains largely unknown. In this study, time-mated Wistar rats (n=18) were orally exposed to 0, 10, 100 or 500 mg/kg bw/day of butylparaben from gestation day 7 to pup day 22. Several endocrine-sensitive endpoints were adversely affected. In the two highest dose groups, the anogenital distance of newborn male and female offspring was significantly reduced, and in prepubertal females, ovary weights were reduced and mammary gland outgrowth was increased. In male offspring, sperm count was significantly reduced at all doses from 10 mg/kg bw/day. Testicular CYP19a1 (aromatase) expression was reduced in prepubertal, but not adult animals exposed to butylparaben. In adult testes, Nr5a1 expression was reduced at all doses, indicating persistent disruption of steroidogenesis. Prostate histology was altered at prepuberty and adult prostate weights were reduced in the high dose group. Thus, butylparaben exerted endocrine disrupting effects on both male and female offspring. The observed adverse developmental effect on sperm count at the lowest dose is highly relevant to risk assessment, as this is the lowest observed adverse effect level in a study on perinatal exposure to butylparaben.
机译:对羟基苯甲酸酯包含通常添加到化妆品,乳液和其他消费产品中的一组防腐剂。对羟基苯甲酸丁酯具有雌激素和抗雄激素特性,已知会降低围产期暴露后大鼠的精子数量。然而,对羟基苯甲酸丁酯的暴露是否会影响其他内分泌敏感的终点,目前仍然未知。在这项研究中,从妊娠第7天到幼犬第22天,定时交配的Wistar大鼠(n = 18)口服暴露于0、10、100或500 mg / kg bw /天的对羟基苯甲酸丁酯/天,对一些对内分泌敏感的终点受到不利影响。在两个最高剂量组中,新生雄性和雌性后代的生殖器距离明显减少,而青春期前雌性的卵巢重量减少,乳腺增生增加。在雄性后代中,所有剂量的精子数量均从10 mg / kg bw /天显着降低。青春期前,睾丸中的CYP19a1(芳香化酶)表达降低,但暴露于对羟基苯甲酸丁酯的成年动物未降低。在成年睾丸中,Nr5a1表达在所有剂量下均降低,表明类固醇生成持续受到破坏。高剂量组在青春期前改变了前列腺组织学,降低了成人前列腺的重量。因此,对羟基苯甲酸丁酯对雄性和雌性后代均具有内分泌干扰作用。在最低剂量下观察到的对精子数量的不利发展影响与风险评估高度相关,因为这是围产期对羟基苯甲酸丁酯暴露研究中观察到的最低不利影响水平。

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