Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: October 1, 2010
Publication Date: March 1, 2011
Citation: Voss, K.A., Riley, R.T., Gelineau-Van Waes, J.B. 2011. Fumonisins. In: Gupta, R., editor. Reproductive and Developmental Toxicology. USA: Elsevier. p. 725-737. Interpretive Summary: Fumonisins are fungal toxins that are found in corn and in foods made from corn. They are toxic to animals but their impact on human health is unclear. The potential role of fumonisins as developmental toxins is reviewed. Some experiments suggest that they do not cause birth defects in laboratory animals although, at high doses, they can cause delayed fetal development or death. However, epidemiological (Missmer et al. 2006) and other experimental (Gelineau-van Waes et al 2005) evidence suggests that fumonisins increase the risk of serious birth defects known as neural tube defects in humans who regularly consume fumonisin-contaminated corn. Fumonisin B1, the most common fumonisin, induces neural tube defects when injected into mice at a critical time during pregnancy. It also disrupts lipid metabolism in the pregnant females and embryos by inhibiting a specific enzyme, ceramide synthase. As a result, lipid metabolism is disrupted, which in turn affects multiple metabolic pathways that are critical for normal fetal development, including the uptake and utilization of folate. Results of these developmental toxicity studies in mice provide a basis for comparative and mechanistic investigations to determine if fumonisins are a risk factor for neural tube defects or other birth anomalies in humans.
Technical Abstract: Fumonisins are mycotoxins produced by Fusarium verticillioides. They occur in corn (maize) and corn-based foods. Their effects on human health are not certain; however, epidemiological and experimental evidence suggests that they increase the risk of neural tube defects (NTDs) in populations routinely consuming large amounts of food prepared from contaminated corn. The developmental effects of fumonisins in F. verticillioides culture material and fumonisin B1 (FB1), the most prevalent fumonisin, have been studied in multiple laboratory animal species. Some results indicate that FB1 and other fumonisins cause maternal toxicity and delayed fetal development or mortality, but are not teratogenic. In contrast, FB1 caused neural tube defects in the offspring of the LM/Bc and CD1 mouse strains when administered to the dams during the critical time for neural tube closure (embryonic days 7-8.5). The etiology of NTDs is complex and likely involves generalized growth retardation as well as specific metabolic and signaling pathways in the embryonic neuroepithelium. Taken together, the studies suggest that disruption of sphingolipid metabolism by FB1 leading to depletion of complex sphingolipids associated with the folate binding protein (Folr1) is one probable mechanistic trigger underlying NTD induction in mice.