ABSTRACT
CONTENTS 5.1 Introduction ............................................................................................... 107 5.2 Fumonisins and Sphingolipid Metabolism .......................................... 108
5.2.1 Ceramide Synthase Inhibition .................................................... 108 5.2.2 Toxicological Implications of Sphingolipid
Metabolism Disruption ................................................................ 110 5.3 Diseases in Farm Animals....................................................................... 111
5.3.1 Equine Leukoencephalomalacia ................................................. 111 5.3.1.1 Clinical Course and Pathology.................................... 111 5.3.1.2 Experimental Findings.................................................. 111
5.3.2 Porcine Pulmonary Edema.......................................................... 112 5.3.2.1 Clinical and Pathological Findings ............................. 112 5.3.2.2 Mechanistic Aspects ...................................................... 112
5.3.3 Other Species ................................................................................. 113 5.4 Toxicological Effects in Laboratory Animals ....................................... 113
5.4.1 Subchronic Toxicity and Pathological Findings ...................... 113 5.4.2 Carcinogenicity.............................................................................. 116
5.5 Neural Tube Defects................................................................................. 117 5.5.1 Observations Implicating Fumonisins as a Risk Factor ......... 117 5.5.2 Mechanistic Hypothesis............................................................... 118 5.5.3 Mouse Models ............................................................................... 118
5.6 Summary and Conclusion....................................................................... 119 References ........................................................................................................... 119
Fusarium verticillioides (formerly F. moniliforme Sheldon) causes sporadic outbreaks of equine leukoencephalomalacia (ELEM)1-4 and porcine pulmonary
edema (PPE).4-6 F. verticillioides is nephrotoxic and hepatotoxic to multiple species and causes liver tumors in rats.4,7-9 The importance of F. verticillioides to human health is not clear although a correlation between high esophageal cancer rates and consumption of corn contaminated with F. verticillioides has long been recognized.10,11 More recent observations suggest that fumonisins might increase the risk of neural tube defects under some conditions.12,13
The discovery of fumonisins B1 (FB1), FB2, FA1, and FA2 14 was a major
advance in understanding the toxicity of F. verticillioides and F. proliferatum, the other major fumonisin-producing fungus, and the list of fumonisin homologues and reaction products continues to grow.15 Fumonisins, like F. verticillioides, have worldwide distribution in corn. They are relatively stable under most cooking conditions and are therefore found in corn-based foods.11,15 While found in low amounts, generally <1 ppm, in commercial corn-based products from industrialized countries, fumonisin concentrations in corn intended for human consumption in some regions can be high,11,15 at times exceeding levels that are toxic to animals. Persons consuming high amounts of corn for cultural or medical (for example, those who must avoid wheat) considerations are potentially subject to relatively high fumonisin intakes.
