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Although deep-fried foods are very popular, the safety of oxidized frying oil (OFO), which is ingested with fried food, is a concern. Consequently, food safety regulations in many countries set an upper limit of 25% polar compounds (PC). The PC comprises all oxidatively altered components in used oils; they may be regarded as a xenobiotic or endocrine-disrupting chemical, as they activate PPARa and induce expression of detoxifying cytochrome P450 monoxygenase and phase II conjugation enzymes to facilitate their own catabolism. Recently, we reported that pregnant C57BL/6J mice fed PC had a higher incidence of fetuses with congenital malformations. This review summarizes the chemical reactions and PC composition in OFO, effects of PC on modulating transcriptional activity of xenobiotic receptors including aryl hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor and PPARa, the importance of retinoic acid (RA) in organogenesis of developing embryos, as well as teratogenic effects of PC. Plausible underlying mechanisms are also discussed. We speculate that the pathogenesis of congenital malformations is disturbed RA metabolism via crosstalks between xenobiotic receptors.