TCDD TERATOGENICITY--MODULATION IN MIXTURES

TCDD（2，3，7，9-tetrachlorodibenzo-p-dioxin）是一种有效的发展 在所有物种中检测到的毒素，在远低于 母亲的LD。然而，致畸作用仅被证明是 在敏感品系的小鼠中，TCDD导致肾积水和裂 在极低的剂量下。近似的化合物 TCDD的等立体异构体也会引起这些畸形， 剂量反应曲线因此，四种不同的多氯联苯 二苯并呋喃和至少一种PCB的混合物可以表示为二苯并呋喃和至少一种PCB的稀释物。 TCDD的毒性。与这些化学品的联合处理也会导致 在一个附加的反应。然而，2，4，5，2 '4' 5 '-六氯- 联苯（HCB）可拮抗TCDD的致畸作用， 浓度窗口窄。六氯苯本身可导致肾积水， 但即使剂量高达 1g/kg。与TCDD联合应用，可阻断裂孔的形成 腭和肾积水，但这些拮抗作用的比例 是不同的.这种拮抗作用的机制仍有待确定。 溴化二恶英和呋喃也是环境污染物， 职业危害，在结构上密切相关的氯化 同源物。2，3，7，8-TBDD的发育毒性和致畸性， 2，3，7，8-TBDF、2，3，4，7，8-PeBDF和1，2，3，7，8，-PeBDF分别在 C57 BL/6 N小鼠。这些化合物产生的效果与 用TCDD观察，特别是腭裂和肾积水。在高 剂量时，还观察到胎仔胸腺萎缩。TBDD约为1/5， TBDF与TBDD的药效相当。这不同于 TCDF的相对致畸性为TCDD的1/20-1/30。 两种PEBDFs的致畸性大致相同，效力为1/20 作为TBDD。因此，较大溴原子的存在似乎增强了 TBDF的毒性，相对于TCDF，但降低毒性， 2，3，4，7，8-五溴二苯醚相对于其氯化同系物的相对含量。

TCDD (2,3,7,9-tetrachlorodibenzo-p-dioxin) is a potent developmental toxin in all species examined, causing fetal toxicity at doses well below the maternal LD. However, teratogenic effects have only been demonstrated in sensitive strains of mice where TCDD causes hydronephrosis and cleft palate at extremely low doses. Compounds which are approximate isostereomers of TCDD also cause these malformations and exhibit parallel dose response curves. Thus, the potency of four different polychlorinated dibenzofurans and at least one PCB can be expressed as dilutions of the toxicity of TCDD. Combination treatment with these chemicals also results in an additive response. however, a PCB such as 2,4,5,2'4'5'-hexachloro- biphenyl (HCB) can antagonize the teratogenic effects of TCDD over a very narrow window of concentrations. HCB by itself can cause hydronephrosis, but it does not appear to cause cleft palate even at doses as high as 1g/kg. In combination with TCDD, it can block the induction of cleft palate and hydronephrosis, but the ratios for these antagonistic effects are different. The mechanism of this antagonism remains to be determined. The brominated dioxins and furans, which are also environmental and occupational hazards, are closely related in structure to the chlorinated congeners. The developmental toxicity and teratogenicity of 2,3,7,8-TBDD, 2,3,7,8-TBDF, 2,3,4,7,8-PeBDF, and 1,2,3,7,8,-PeBDF were examined in C57BL/6N mice. These compounds produced the same spectrum of effects as observed with TCDD, specifically cleft palate and hydronephrosis. At high doses, fetal thymic atrophy was also noted. TBDD was approximately 1/5 as potent as TCDD, while TBDF was equipotent to TBDD. This is in contrast to the relative teratogenicity of TCDF which is 1/20-1/30 as potent as TCDD. The two PeBDFs are approximately equiteratogenic and are 1/20 as potent as TBDD. Thus, the presence of the larger bromine atom appears to enhance the toxicity of TBDF, relative to TCDF, but decrease the toxicity of 2,3,4,7,8-PeBDF relative to its chlorinated congener.