Critical review of the developmental toxicity and teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: Recent advances toward understanding the mechanism
A specific teratogenic response is elicited in the mouse as a result of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin). The characteristic spectrum of structural malformations induced in mice following exposure to TCDD and structurally-related congeners is highly reproducible and includes both hydronephrosis and cleft palate. In addition, prenatal exposure to TCDD has been shown to induce thymic hypoplasia. The three abnormalities occur at doses well below those producing maternal or embryo/fetal toxicity, and are among the most sensitive indicators of dioxin toxicity. In all other laboratory species tested, TCDD causes maternal and embryo/fetal toxicity, but does not induce a significant increase in the incidence of structural abnormalities even at toxic dose levels. Developmental toxicity occurs in a similar dose range across species, however, mice are particularly susceptible to development of TCDD-induced terata. Recent experiments using an organ culture were an attempt to address the issue of species and organ differences in sensitivity to TCDD. Human palatal shelves were examined in this in vitro system, and were found to approximate the rat in terms of sensitivity for induction of cleft palate.
- Research Organization:
- Environmental Protection Agency, Research Triangle Park, NC (United States). Health Effects Research Lab.
- OSTI ID:
- 5458577
- Report Number(s):
- PB-91-211383/XAB
- Resource Relation:
- Other Information: Pub. in Teratology, v42 n6 p619-627 1990. Prepared in cooperation with National Inst. of Environmental Health Sciences, Research Triangle Park, NC., and North Carolina Univ. at Chapel Hill
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DIOXIN
TERATOGENESIS
GENETIC VARIABILITY
MAN
MICE
PRENATAL EXPOSURE
RATS
ANIMALS
BIOLOGICAL VARIABILITY
HETEROCYCLIC COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PRIMATES
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology