Gaido K, Dohme L, Wang F, Chen I, Blankvoort B, Ramamoorthy K, Safe S
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina, USA.
Environ Health Perspect. 1998 Dec;106 Suppl 6(Suppl 6):1347-51. doi: 10.1289/ehp.98106s61347.
The human diet contains industrial-derived, endocrine-active chemicals and higher levels of naturally occurring compounds that modulate multiple endocrine pathways. Hazard and risk assessment of these mixtures is complicated by noadditive interactions between different endocrine-mediated responses. This study focused on estrogenic chemicals in the diet and compared the relative potencies or estrogen equivalents (EQs) of the daily consumption of xenoestrogenic organochlorine pesticides in food (2.44 micrograms/day) with the EQs in a single 200-ml glass of red cabernet wine. The reconstituted organochlorine mixture contained 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethane, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, endosulfan-1, endosulfan-2, p,p'-methoxychlor, and toxaphene; the relative proportion of each chemical in the mixture resembled the composition reported in a recent U.S. Food and Drug Administration market basket survey. The following battery of in vitro 17 beta-estradiol (E2)-responsive bioassays were utilized in this study: competitive binding to mouse uterine estrogen receptor (ER); proliferation in T47D human breast cancer cells; luciferase (Luc) induction in human HepG2 cells transiently cotransfected with C3-Luc and the human ER, rat ER-alpha, or rat ER-beta; induction of chloramphenicol acetyltransferase (CAT) activity in MCF-7 human breast cancer cells transfected with E2-responsive cathepsin D-CAT or creatine kinase B-CAT plasmids. For these seven in vitro assays, the calculated EQs in extracts from 200 ml of red cabernet wine varied from 0.15 to 3.68 micrograms/day. In contrast, EQs for consumption of organochlorine pesticides (2.44 micrograms/day) varied from nondetectable to 1.24 ng/day. Based on results of the in vitro bioassays, organochlorine pesticides in food contribute minimally to dietary EQ intake.
人类饮食中含有工业源的、具有内分泌活性的化学物质以及更高水平的可调节多种内分泌途径的天然化合物。不同内分泌介导反应之间的非加性相互作用使得对这些混合物的危害和风险评估变得复杂。本研究聚焦于饮食中的雌激素化学物质,并比较了食物中异雌激素有机氯农药每日摄入量(2.44微克/天)的相对效力或雌激素当量(EQs)与一杯200毫升赤霞珠红葡萄酒中的EQs。重构的有机氯混合物包含1,1,1-三氯-2-(对氯苯基)-2-(邻氯苯基)乙烷、1,1,1-三氯-2,2-双(对氯苯基)乙烷、1,1-二氯-2,2-双(对氯苯基)乙烯、硫丹-1、硫丹-2、p,p'-甲氧滴滴涕和毒杀芬;混合物中每种化学物质的相对比例类似于美国食品药品监督管理局近期市场篮子调查中报告的组成。本研究使用了以下一系列体外17β-雌二醇(E2)反应性生物测定法:与小鼠子宫雌激素受体(ER)的竞争性结合;T47D人乳腺癌细胞中的增殖;用C3-荧光素酶和人ER、大鼠ER-α或大鼠ER-β瞬时共转染的人HepG2细胞中的荧光素酶(Luc)诱导;用E2反应性组织蛋白酶D-氯霉素乙酰转移酶(CAT)或肌酸激酶B-CAT质粒转染的MCF-7人乳腺癌细胞中氯霉素乙酰转移酶(CAT)活性的诱导。对于这七种体外测定法,200毫升赤霞珠红葡萄酒提取物中计算出的EQs在0.15至3.68微克/天之间变化。相比之下,有机氯农药摄入量(2.44微克/天)的EQs在未检出至1.24纳克/天之间变化。基于体外生物测定结果,食物中的有机氯农药对膳食EQ摄入量的贡献极小。