Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark.
Toxicol Appl Pharmacol. 2011 Feb 1;250(3):278-90. doi: 10.1016/j.taap.2010.10.031. Epub 2010 Nov 6.
Octyl Methoxycinnamate (OMC) is a frequently used UV-filter in sunscreens and other cosmetics. The aim of the present study was to address the potential endocrine disrupting properties of OMC, and to investigate how OMC induced changes in thyroid hormone levels would be related to the neurological development of treated offspring. Groups of 14-18 pregnant Wistar rats were dosed with 0, 500, 750 or 1000 mg OMC/kg bw/day during gestation and lactation. Serum thyroxine (T(4)), testosterone, estradiol and progesterone levels were measured in dams and offspring. Anogenital distance, nipple retention, postnatal growth and timing of sexual maturation were assessed. On postnatal day 16, gene expression in prostate and testes, and weight and histopathology of the thyroid gland, liver, adrenals, prostate, testes, epididymis and ovaries were measured. After weaning, offspring were evaluated in a battery of behavioral and neurophysiological tests, including tests of activity, startle response, cognitive and auditory function. In adult animals, reproductive organ weights and semen quality were investigated. Thyroxine (T(4)) levels showed a very marked decrease during the dosing period in all dosed dams, but were less severely affected in the offspring. On postnatal day 16, high dose male offspring showed reduced relative prostate and testis weights, and a dose-dependent decrease in testosterone levels. In OMC exposed female offspring, motor activity levels were decreased, while low and high dose males showed improved spatial learning abilities. The observed behavioral changes were probably not mediated solely by early T(4) deficiencies, as the observed effects differed from those seen in other studies of developmental hypothyroxinemia. At eight months of age, sperm counts were reduced in all three OMC-dosed groups, and prostate weights were reduced in the highest dose group. Taken together, these results indicate that perinatal OMC-exposure can affect both the reproductive and neurological development of rat offspring, which may be a cause of concern, as humans are systematically exposed to the compound through usage of sunscreens and other cosmetics.
辛基甲氧基肉桂酸酯(OMC)是防晒霜和其他化妆品中常用的紫外线滤光剂。本研究的目的是研究 OMC 的潜在内分泌干扰特性,并探讨 OMC 诱导的甲状腺激素水平变化与受处理后代的神经发育之间的关系。将 14-18 只怀孕的 Wistar 大鼠分为 0、500、750 或 1000mg OMC/kg bw/day 剂量组,在妊娠和哺乳期进行给药。测量母鼠和子代的血清甲状腺素(T4)、睾酮、雌二醇和孕酮水平。评估肛门生殖器距离、乳头保留、产后生长和性成熟时间。在产后第 16 天,测量前列腺和睾丸的基因表达,以及甲状腺、肝脏、肾上腺、前列腺、睾丸、附睾和卵巢的重量和组织病理学。断奶后,对后代进行一系列行为和神经生理测试,包括活动、惊跳反应、认知和听觉功能测试。在成年动物中,研究了生殖器官重量和精液质量。在所有给药的母鼠中,甲状腺素(T4)水平在给药期间都有明显下降,但在子代中受影响较小。在产后第 16 天,高剂量雄性后代的前列腺和睾丸相对重量降低,睾酮水平呈剂量依赖性降低。在暴露于 OMC 的雌性后代中,运动活动水平降低,而低剂量和高剂量雄性的空间学习能力提高。观察到的行为变化可能不仅仅是由早期 T4 缺乏引起的,因为观察到的影响与其他甲状腺功能减退症发育研究中观察到的影响不同。在 8 个月时,所有三个 OMC 给药组的精子计数均减少,最高剂量组的前列腺重量减少。综上所述,这些结果表明,围产期 OMC 暴露会影响大鼠后代的生殖和神经发育,这可能是一个令人担忧的问题,因为人类通过使用防晒霜和其他化妆品系统地暴露于该化合物。