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CJ Calvano, LT Muller, R LeFevre, CK Mishra, CA Gunderson, RF Mankes; Fetal Alcohol Syndrome and Microphthalmia: Structure-activity Relationship of Ethanol and 2-Halogenated Ethanols . Invest. Ophthalmol. Vis. Sci. 2002;43(13):211.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Fetal Alcohol Syndrome (FAS) is a triad of mental and growth retardation, and facial dysmorphology including microphthalmia. Ethanol is a well described teratogen and halogenation has been shown to effect metabolism; evaluating halogenated ethanols may help us to understand the mechanism of the teratogenic effects. We sought to examine the mechanism of ethanol associated microphthalmia by studying 2-halogentated ethanols as compared to ethanol to generate a structure-activity as well as dose-response relationships. Methods: Time-pregnant Long Evans rats were dosed from day 6-15 of gestation with ethanol and haloethanols (2-F, 2-Br, 2-Cl). Dosages were selected as fractions of the oral LD50 for each alcohol. Litters were derived by cesarian section at day 20. Standard teratology measures were recorded. Anomalies including microphthalmia were determined by Wilson serial sectioning. Results: Data in Table presented as #affected fetuses-#affected litters. *p<0.05 by Multi-way ANOVA. All experimental groups had significant growth retardation as evidenced by birth weight depression and crown-rump length preservation. Maternal toxicity was not evident at the doses selected. Conclusion: Growth retardation is a hallmark of rodent FAS models and was present in all experimental groups. Fluorine is the most electronegative halogen, and was associated with the lowest incidence of microphthalmia. Generally, as electronegativity decreased, the incidence of ocular growth retardation increased. Further quantifying the mechanism of ethanol and halogenated ethanol and their teratogenic effects will help us to further understand fetal alcohol syndrome. Incidence of microphthalmia in fetal rats exposed to various ethanols during organogenesis as determ View OriginalDownload SlideView OriginalDownload Slide
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