TCDD TERATOGENICITY--MODULATION IN MIXTURES

TCDD（2,3,7,8-四氯二苯并-对二恶英）是毒性最大的

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.