TCDD TERATOGENICITY--MODULATION IN MIXTURES

TCDD(2，3，7，8-四氯二苯并-对二恶英)毒性最强 已知的人造化学物质。TCDD已经被证明是高度的 在多种物种中都有致畸作用。在小鼠中，TCDD会导致裂隙 味觉和肾积水无明显毒性的剂量 在母亲身上很明显。我们最近发现， 肾积水是由于肾小管上皮细胞受到影响而引起的。 发育中的肾脏，一种比裂隙更敏感的反应 味觉。小鼠的模式或致畸作用是这样的 TCDD的特点是它可以作为一种方法 确定化合物是否为类TCDD。我们 已经能够证明几种多氯化物质 二苯并呋喃，2，3，7，8-四氯二苯并呋喃，1，2，3，7，8- 五氯二苯并呋喃(1-PeCDF)，2，3，4，7，8-PeCDF(4-PeCDF)， 和1，2，3，4，7，8-六氯二苯并呋喃(HCDF)都会引起裂隙 发育中的小鼠胎儿的腭部和肾积水。一个 持久性和公共环境多氯联苯，2，3，4，5，3‘，4’- 六氯联苯(HCB)也会引起同样的反应。因此，所有的 这些化学物质的效力系数可以被指定为1，相对 TCDF、1-PeCDF、4-PeCDF、HCDF和HCB的效价为0.05， .03、.1、.01和.00003。这些化合物的组合结果 除了影响的可加性，支持了这样的结论 化学品通过一种共同的机制起作用。其他化合物 被认为是类似TCDD的病毒也在调查中。 全氟酸--一种长链全氟脂肪酸 被开发为潜在的阻燃剂，导致胸腺 萎缩、消瘦和延迟致死。然而，它并没有 导致腭裂或肾积水。目前的研究也 表明其毒性不与Ah位点分离。在……里面 此外，用PFDA治疗小鼠不会导致 甲状腺激素水平下降，这是继 接触TCDD。因此，我们认为PFDA不是二恶英。 模拟的。

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is the most toxic man-made chemical known. TCDD has been shown to be highly teratogenic in multiple species. In the mouse, TCDD causes cleft palate and hydronephrosis at doses where no overt toxicity is evident in the mother. We have recently discovered that hydronephrosis is caused by an effect on the epithelial cells of the developing kidney, a response which is more sensitive than cleft palate. The pattern or teratogenic effects in the mouse is so characteristic of TCDD that it can be used as a method of determining whether or not compounds are TCDD-like or not. We have been able to demonstrate that several polychlorinated dibenzofurans, 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8- pentachlorodibenzofuran (1-PeCDF), 2,3,4,7,8-PeCDF (4-PeCDF), and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) all cause cleft palate and hydronephrosis in the developing mouse fetus. A persistent and common environmental PCB, 2,3,4,5,3',4'- hexachlorobiphenyl (HCB) causes the same response. Thus, all of these chemical can be assigned a potency factor of 1, the relative potencies of TCDF, 1-PeCDF, 4-PeCDF, HCDF, and HCB are .05, .03, .1, .01, and .00003. Combination of these compounds results in additivity of effects, supporting the conclusion that these chemicals act by a common mechanism. Other compounds which have been suggested to be TCDD-like are also under investigation. Perfluorodecanoic acid, a long chain-totally fluorinated fatty acid developed for potential use as a flame retardant, causes thymic atrophy, wasting, and delayed lethality. However, it does NOT cause cleft palate or hydronephrosis. Current studies also indicate that its toxicity does not segregate with the Ah locus. In addition, treatment of mice with PFDA does not cause a depression in thyroid hormone levels, another effect seen after TCDD exposure. Thus, we conclude that PFDA is not a dioxin analog.