Schlumpf Margret, Schmid Peter, Durrer Stefan, Conscience Marianne, Maerkel Kirsten, Henseler Manuel, Gruetter Melanie, Herzog Ingrid, Reolon Sasha, Ceccatelli Raffaella, Faass Oliver, Stutz Eva, Jarry Hubertus, Wuttke Wolfgang, Lichtensteiger Walter
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Toxicology. 2004 Dec 1;205(1-2):113-22. doi: 10.1016/j.tox.2004.06.043.
UV filters represent a new class of endocrine active chemicals. In vitro, 8/9 chemicals showed estrogenic (MCF-7 cells), and 2/9 antiandrogenic activity (MDA-kb2 cells). Six/nine filters (benzophenone (Bp)-1, Bp-2, Bp-3, 3-benzylidene camphor (3-BC), 4-methylbenzylidene camphor (4-MBC), octyl-methoxycinnamate (OMC)) increased uterine weight in immature rats. 3-Benzylidene camphor and 4-MBC displaced 16alpha125I-estradiol from human estrogen receptor (ER)beta, not ERalpha. Developmental toxicity of 4-MBC (0.7-47 mg/kg body weight/day) and 3-BC (0.24-7 mg/kg), administered in chow was investigated in Long Evans (LE) rats. Weight gain of pregnant rats was reduced only by 3-BC, early postnatal survival rate and thymus weight by both compounds at higher doses. 4-Methylbenzylidene camphor and 3-BC delayed male puberty, and dose-dependently affected reproductive organ weights of adult male and female F1 offspring, with partly different effect patterns. Thyroid weight was increased by higher 4-MBC doses. Tissue-specific changes in mRNA levels of estrogen-regulated genes in prostate, uterus and brain regions, determined by real-time PCR, and in their response to acute estradiol challenge in adult gonadectomized offspring were observed. Lowest effective doses were 0.24 mg/kg/day for 3-BC and 7 mg/kg/day for 4-MBC. Fat tissue levels at 7 mg/kg 4-MBC (GC-MS) approached the range of UV filters in fish (Nagtegaal et al., 1997; Balmer et al., 2004).
紫外线过滤剂是一类新型的内分泌活性化学物质。在体外实验中,9种化学物质中的8种表现出雌激素活性(MCF-7细胞),2种表现出抗雄激素活性(MDA-kb2细胞)。9种过滤剂中的6种(二苯甲酮(Bp)-1、Bp-2、Bp-3、3-苄叉樟脑(3-BC)、4-甲基苄叉樟脑(4-MBC)、桂皮酸盐(OMC))可增加未成熟大鼠的子宫重量。3-苄叉樟脑和4-MBC可使人雌激素受体(ER)β而非ERα上的16α125I-雌二醇发生位移。研究了在Long Evans(LE)大鼠的食物中添加4-MBC(0.7-47毫克/千克体重/天)和3-BC(0.24-7毫克/千克)的发育毒性。仅3-BC可降低怀孕大鼠的体重增加,两种化合物在高剂量时均可降低出生后早期存活率和胸腺重量。4-甲基苄叉樟脑和3-BC延迟了雄性青春期,并剂量依赖性地影响成年雄性和雌性F1后代的生殖器官重量,其影响模式部分不同。较高剂量的4-MBC可增加甲状腺重量。通过实时PCR测定了前列腺、子宫和脑区中雌激素调节基因的mRNA水平的组织特异性变化,并观察了成年去势后代对急性雌二醇刺激的反应。3-BC的最低有效剂量为0.24毫克/千克/天,4-MBC为7毫克/千克/天。4-MBC剂量为7毫克/千克时脂肪组织中的含量(气相色谱-质谱法)接近鱼类体内紫外线过滤剂的含量范围(Nagtegaal等人,1997年;Balmer等人,2004年)。