Seidlová-Wuttke D, Jarry H, Christoffel J, Rimoldi G, Wuttke W
Department of Clinical and Experimental Endocrinology, University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
Toxicol Appl Pharmacol. 2006 Feb 1;210(3):246-54. doi: 10.1016/j.taap.2005.05.006. Epub 2005 Jun 27.
OMC and 4MBC are 2 absorbers of ultraviolet light which are used in unknown quantities in sunscreens, cosmetics and plastic products to protect against UV light-induced damage of the skin or of fragrances or plastic material. From there, they were shown to reach surface water and/or by direct contamination or ingestion the human. Under various conditions in mice and rats, both substances were shown to be estrogenic. Therefore, we compared in vitro and in vivo the effects of chronic application of these compounds at 2 doses with those of E2, all administered via food. No signs of toxicity were observed under application of 0.6 mg E2, 57.5 or 275 mg of OMC, 57.5 or 250 mg of 4MBC; these amounts were ingested with 21 g of control food, 17.8 g E2 food, 20.6 g or 22.3 g OMC food and 23.7 or 22.8 g 4MBC food. In the uterus, vagina and bone, E2 exerted the expected stimulatory effects which were minimally shared by OMC and 4MBC in the uterus and vagina as assessed by histology and determination of a variety of estrogen-regulated genes such as insulin-like growth factor-1, progesterone receptor and estrogen receptor beta. In the bone, OMC had no effect, while 4MBC shared the antiosteoporotic effects of E2 as measured by quantitative computer tomography in the metaphysis of the tibia. The mechanism of action of 4MBC, however, appears to be different as E2 reduced serum osteocalcin and the C-terminal breakdown products of collagen-1alpha1 which were both increased by 4MBC. Taken together, these data indicate a very weak estrogenic effect of OMC and 4MBC in the uterus and in the vagina but not in the bone where 4MBC exerted antiosteoporotic effects by a different mechanism than E2.
二苯甲酰甲烷(OMC)和4-甲基二苯甲酰甲烷(4MBC)是两种紫外线吸收剂,在防晒霜、化妆品和塑料制品中用量不明,用于防止紫外线对皮肤、香料或塑料材料造成损伤。研究表明,它们可通过直接污染或人体摄入进入地表水。在小鼠和大鼠的各种实验条件下,这两种物质均表现出雌激素活性。因此,我们通过食物分别以两种剂量对这些化合物与雌二醇(E2)进行了慢性给药,并比较了它们在体外和体内的作用。给予0.6毫克E2、57.5或275毫克OMC、57.5或250毫克4MBC时,未观察到毒性迹象;这些剂量分别通过21克对照食物、17.8克E2食物、20.6克或22.3克OMC食物以及23.7克或22.8克4MBC食物摄入。在子宫、阴道和骨骼中,E2产生了预期的刺激作用;通过组织学检查以及测定多种雌激素调节基因(如胰岛素样生长因子-1、孕激素受体和雌激素受体β)发现,OMC和4MBC在子宫和阴道中仅有微弱的类似作用。在骨骼方面,OMC无作用,而通过定量计算机断层扫描测量胫骨干骺端发现,4MBC具有与E2相同的抗骨质疏松作用。然而,4MBC的作用机制似乎有所不同,因为E2可降低血清骨钙素以及1型胶原蛋白α1的C端降解产物,而4MBC则使其升高。综上所述,这些数据表明,OMC和4MBC在子宫和阴道中具有非常微弱的雌激素活性,而在骨骼中,4MBC通过与E2不同的机制发挥抗骨质疏松作用。