Fusarium mycotoxins and human health. Review.
Gordon S. Shephard
gordon.shephard@mrc.ac.zaPROMEC Unit, Medical Research Council, PO Box 19070, Tygerberg 7505, South Africa (South Africa)
Abstract
Species within the genus Fusarium produce a diverse range of mycotoxins, many of which have signifi- cant impacts on human health. Of the five generally recognised major mycotoxins, three (fumonisins, de- oxynivalenol (DON) and zearalenone (ZON)) are produced by Fusaria. Apart from DON, other trichothecenes such as T-2 toxin, have received considerable international attention due to their impact on human health. The fumonisins, which occur ubiquitously in maize and its products, have been linked to oesophageal cancer, liver cancer and neural tube defects. DON, a frequent contaminant of maize, wheat and their products, although showing no carcinogenic potential, is immunomodulatory and produces emesis and growth retardation in animals. ZON is a naturally occurring endocrine disrupting chemical. Acute exposure to these mycotoxins has in each case been linked to outbreaks of human disease – gastro-intestinal effects in the case of fumonisins and DON, and precocious pubertal changes in the case of ZON. Concern over their toxicological effects has led to risk assessments by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), which has set maximum tolerable daily intakes (TDI) of 2 µg/ kg body weight (bw) for fumonisins and 0.5 µg/kg bw for ZON. The initial TDI set for DON, namely 1 µg/kg bw has recently been updated by JECFA to include both 3- and 15-acetylDON. Apart from the above mycotoxins, a number of other secondary metabolites (moniliformin, beauvericin and fusaproliferin) are produced by different Fusaria and their effects on human health, either alone or in combination with other mycotoxins, is largely unexplored.
Keywords:
cancer, deoxynivalenol, Fumonisin, T-2 toxin, trichothecenes zearalenoneReferences
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Bhat R.V., Shetty P.H., Amruth R.P., Sudershan R.V., 1997. A foodborne disease outbreak due to the consumption of moldy sorghum and maize containing fumonisin mycotoxins. J. Toxicol. Clinical Toxicol. 35: 249-255.
Bolger M., Coker R.D., DiNovi M., Gaylor D., Gelderblom W., Olsen M., Paster N., Riley R.T., Shephard G., Speijers G.J.A., 2001. Fumonisins. In: Safety Evaluation of Certain Mycotoxins in Food. WHO Food Additives Series 47, FAO Food and Nutrition Paper 74, Prepared by the 56th Meeting of the Joint FAO/ WHO Expert Committee on Food Additives (JECFA). WHO, Geneva, Switzerland, pp. 103-279.
Campbell, G.D., 1991. Trichothecene mycotoxicosis – a new entity? South Afr. Med. J. 80: 361-362.
Canady R.A., Coker R.D., Egan S.K., Krska R., Kuiper-Goodman T., Olsen M., Pestka J., Resnik S., Schlatter J., 2001a. Deoxynivalenol. In: Safety Evaluation of Certain Mycotoxins in Food. WHO Food Additives Series 47, FAO Food and Nutrition Paper 74, WHO, Geneva, Switzerland, pp. 419-555.
Canady R.A., Coker R.D., Egan S.K., Krska R., Olsen M., Resnik S., Schlatter J., 2001b. T-2 and HT-2 toxins. In: Safety Evaluation of Certain Mycotoxins in Food. WHO Food Additives Series 47, FAO Food and Nutrition Paper 74, WHO, Geneva, Switzerland, pp. 557-680.
CAST, Council for Agricultural Science and Technology, 2003. Mycotoxins: Risks in Plant, Animal, and Human Systems. CAST, Ames, IA, USA.
Feudjio F.T., Dornetshuber R.,Lemmens M., Hoffmann O., Lemmens-Gruber R., Berger W., (2010). Beauvericin and enniatin: emerging toxins and/or remedies? World Mycotoxin J. 3: 415-430.
Gelineau-van Waes J., Starr L., Maddox J., Aleman F., Vos K.A, Wilberding J., Riley R.T., 2005. Maternal fumonisin exposure and risk for neural tube defects: mechanisms in an in vivo mouse model. Birth Defects Res. (part A) 73: 487-497.
Gong Y.Y., Torres-Sanchez L., Lopez-Carrillo L., Peng J.H., Sutcliffe A.E., White K.L., Humpf H.-U., Turner P.C., Wild C.P., 2008. Association between tortilla consumption and human urinary fumonisin B1 levels in a Mexican population. Cancer Epidemiol. Biomarkers Prev. 17: 688-694.
Hsieh D.P.H., 1989. Potential human health hazards of mycotoxins. In: Mycotoxins and Phycotoxins 1988, Natori, S., Hashimoto, K., Ueno, Y., (Eds.), Elsevier, Amsterdam, The Netherlands, pp. 69-80.
IARC, International Agency for Research on Cancer, 1993. WHO IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins. Toxins derived from Fusarium graminearum, F. culmorum and F. crookwellense: zearalenone, deoxynivalenol, nivalenol and fusarenone X. IARC, Lyon, France, 56: 397-444.
IARC, International Agency for Research on Cancer, 2002. WHO IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene. Fumonisin B1. IARC, Lyon, France, 82: 301-366.
JECFA, 2000. 53rd Meeting of the Joint FAO/WHO Expert Committee on Food Additives. http://www.inchem.org/documents/jecfa/jecmono/v44jec14.htm Accessed 13 April 2010.
JECFA, 2010. 72nd Meeting of the Joint FAO/WHO Expert Committee on Food Additives. http://www.who.int/entity/foodsafety/chem/summary72_rev.pdf Accessed 8 April 2010.
Luo X.Y., 1988. Outbreaks of moldy cereals poisoning in China. In: Issues in Food Safety, Toxicology Forum, Inc., Washington DC, USA, pp. 56-63.
Marasas W.F.O., Nelson P.E., 1987a. Hemorrhagic Syndrome. In: Mycotoxicology. Pennsylvania State University Press, University Park, PA, USA, pp. 41-44.
Marasas W.F.O., Nelson P.E., 1987b. Estrogenic Syndrome. In: Mycotoxicology. Pennsylvania State University Press, University Park, PA, USA, pp. 45-48.
Marasas W.F.O., et al., 2004. Fumonisins disrupt sphingolipid metabolism, folate transport, and neural tube development in embryo culture and in vivo: A potential risk factor for human neural tube defects among populations consuming fumonisin-contaminated maize. J. Nutrition 134: 711-716.
Maresca M., Fantini J., 2010. Some food-associated mycotoxins as potential risk factors in humans predisposed to chronic intestinal inflammatory diseases. Toxicon 56: 282-294.
Massart F., Meucci V., Saggese G., Soldani G., 2008. High growth rate of girls with precocious puberty exposed to estrogenic mycotoxins. J. Pediatr. 152: 690-695.
Merrill A.H. Jr., 1991. Cell regulation by sphingosine and more complex sphingolipids. J. Bioenergetics Biomembranes 23: 83-104.
Miller J.D., 1998. Global significance of mycotoxins. In: Mycotoxins and Phycotoxins – Developments in Chemistry, Toxicology and Food Safety, Miraglia, M., Van Egmond, H.P., Brera, C., Gilbert, J., (Eds.), Alaken, Fort Collins, CO, USA, pp. 3-15.
Missmer S.A., Suarez L., Felkner M., Wang E., Merrill,A.H. Jr., Rothman K.J., Hendricks K.A., 2006. Exposure to fumonisins and the occurrence of neural tube defects along the Texas-Mexico border. Environ. Health Perspect. 114:237-241.
Pascale M., Doko M.B., Visconti A., 1995. Determination of fumonisins in polenta by high performance liquid chromatography. In: Proceedings of the 2nd National Congress on Food Chemistry, GiardiniNaxos, 24-27 May 1995, La Grafica Editoriale, Messina, Italy, pp. 1067-1071.
Pestka J.J., 2008. Mechanisms of deoxynivalenol-induced gene expression and apoptosis. Food Addit. Contam. 25: 1128-140.
Rheeder J.P., Marasas W.F.O., Thiel P.G., Sydenham E.W., Shephard G.S., Schalkwyk D.J. van, 1992. Fusarium moniliforme and fumonisins in corn in relation to human esophageal cancer in Transkei. Phytopathology 82: 353-357.
Rheeder J.P., Marasas W.F.O., Vismer H.F., 2002. Production of fumonisin analogs by Fusarium species. Appl. Environ. Microbiol. 68: 2101-2105.
Saenz de Rodrigues C.A., Bongiovanni A.M., Conde de Borrego L., 1985. An epidemic of precocious development in Puerto Rican children. J. Pediatr. 107: 393-396.
Shephard G.S., Thiel P.G., Stockenström S., Sydenham E.W., 1996. Worldwide survey of fumonisin contamination of corn and corn-based products. J. AOAC Int. 79: 671-687.
Shephard G.S., Westhuizen L. van der , Gatyeni P.M., Katerere D.R., Marasas,W.F.O., 2005. Do fumonisin mycotoxins occur in wheat? J. Agric. Food Chem. 53: 9293-9296.
Shephard G.S., Marasas W.F.O., Burger H.-M., Somdyala N.I.M., Rheeder J.P., Westhuizen L. van der, Gatyeni P., Schalkwyk, D.J. van, 2007a. Exposure assessment for fumonisins in the former Transkei region of South Africa. Food Addit. Contam. 24: 621-629.
Shephard G.S., Westhuizen L. van der, Sewram V., 2007b. Biomarkers of exposure to fumonisin mycotoxins: A review. Food Addit. Contam. 24: 1196-1201.
Stevens V.L., Tang J., 1997. Fumonisin B1-induced sphingolipid depletion inhibits vitamin uptake via the glycosylphosphatidylinositol-anchored folate receptor. J. Biol. Chem. 272: 18020-18025.
Sun G., Wang S., Hu X., Su J., Huang T., Yu J., Tang L., Gao W., Wang J.-S., 2007. Fumonisin B1 contamination of home-grown corn in high-risk areas for esophageal and liver cancer in China. Food Addit. Contam. 24: 181-185.
Szuets P., Mesterhazy A., Falkay G., Bartok T., 1997. Early thelarche symptoms in children and their relations to zearalenone contamination in food stuffs. Cereal Res. Comm. 25: 429-436.
Turner P.C., BurleyV.J., Rothwell J.A., White K.L.M., Cade J.E., Wild C.P., 2008a. Deoxynivalenol: Rationale for development and application of a urinary biomarker. Food Addit. Contam. 25: 864-871.
Turner P.C., Rothwell J.A., White K.L.M., Gong Y., Cade J.E., Wild C.P., 2008b. Urinary deoxynivalenol is correlated with cereal intake in individuals from the United Kingdom. Environ. Health Perspect. 116: 21- 25.
Ueno Y., Iijima K., Wang S.D., Sugiura Y., Sekijima M., Tanaka T., Chen C., Yu S.Z., 1997. Fumonisins as a possible contributory risk factor for primary liver cancer; a 3-year study of corn harvested in Haimen, China by HPLC and ELISA. Food Chem. Toxicol. 35: 1143-1150.
Westhuizen L. van der, Shephard G.S., Scussel V.M., Costa L..L.F., Vismer H..F., Rheeder J.P., Marasas W.F.O., 2003. Fumonisin contamination and Fusarium incidence in corn from Santa Catarina, Brazil. J. Agric. Food Chem. 51: 5574-5578.
Westhuizen L. van der, Shephard G.S., Rheeder J.P., Burger H.-M., 2010. Individual fumonisin exposure and sphingoid base levels in rural populations consuming maize in South Africa. Food Chem. Toxicol. DOI: 10.1016/j.fct.2010.03.047.
Zhang H., Nagashima H., Goto T., 1997. Natural occurrence of mycotoxins in corn samples from high and low risk areas for human esophageal cancer in China. Mycotoxins 44: 29-35.
Zhang A., Cao J.-L., Yang B., Chen J.-H., Zhang Z.-T., Li S.-Y., Fu Q., Hugnes C.E., Caterson B., 2010. Effects of moniliformin and selenium on human articular cartilage metabolism and their potential relationships to the pathogenesis of Kashin-Beck disease. J. Zhejiang Univ. – Sci. B 11: 200-208. Google Scholar
Bhat R.V., Shetty P.H., Amruth R.P., Sudershan R.V., 1997. A foodborne disease outbreak due to the consumption of moldy sorghum and maize containing fumonisin mycotoxins. J. Toxicol. Clinical Toxicol. 35: 249-255.
Bolger M., Coker R.D., DiNovi M., Gaylor D., Gelderblom W., Olsen M., Paster N., Riley R.T., Shephard G., Speijers G.J.A., 2001. Fumonisins. In: Safety Evaluation of Certain Mycotoxins in Food. WHO Food Additives Series 47, FAO Food and Nutrition Paper 74, Prepared by the 56th Meeting of the Joint FAO/ WHO Expert Committee on Food Additives (JECFA). WHO, Geneva, Switzerland, pp. 103-279.
Campbell, G.D., 1991. Trichothecene mycotoxicosis – a new entity? South Afr. Med. J. 80: 361-362.
Canady R.A., Coker R.D., Egan S.K., Krska R., Kuiper-Goodman T., Olsen M., Pestka J., Resnik S., Schlatter J., 2001a. Deoxynivalenol. In: Safety Evaluation of Certain Mycotoxins in Food. WHO Food Additives Series 47, FAO Food and Nutrition Paper 74, WHO, Geneva, Switzerland, pp. 419-555.
Canady R.A., Coker R.D., Egan S.K., Krska R., Olsen M., Resnik S., Schlatter J., 2001b. T-2 and HT-2 toxins. In: Safety Evaluation of Certain Mycotoxins in Food. WHO Food Additives Series 47, FAO Food and Nutrition Paper 74, WHO, Geneva, Switzerland, pp. 557-680.
CAST, Council for Agricultural Science and Technology, 2003. Mycotoxins: Risks in Plant, Animal, and Human Systems. CAST, Ames, IA, USA.
Feudjio F.T., Dornetshuber R.,Lemmens M., Hoffmann O., Lemmens-Gruber R., Berger W., (2010). Beauvericin and enniatin: emerging toxins and/or remedies? World Mycotoxin J. 3: 415-430.
Gelineau-van Waes J., Starr L., Maddox J., Aleman F., Vos K.A, Wilberding J., Riley R.T., 2005. Maternal fumonisin exposure and risk for neural tube defects: mechanisms in an in vivo mouse model. Birth Defects Res. (part A) 73: 487-497.
Gong Y.Y., Torres-Sanchez L., Lopez-Carrillo L., Peng J.H., Sutcliffe A.E., White K.L., Humpf H.-U., Turner P.C., Wild C.P., 2008. Association between tortilla consumption and human urinary fumonisin B1 levels in a Mexican population. Cancer Epidemiol. Biomarkers Prev. 17: 688-694.
Hsieh D.P.H., 1989. Potential human health hazards of mycotoxins. In: Mycotoxins and Phycotoxins 1988, Natori, S., Hashimoto, K., Ueno, Y., (Eds.), Elsevier, Amsterdam, The Netherlands, pp. 69-80.
IARC, International Agency for Research on Cancer, 1993. WHO IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins. Toxins derived from Fusarium graminearum, F. culmorum and F. crookwellense: zearalenone, deoxynivalenol, nivalenol and fusarenone X. IARC, Lyon, France, 56: 397-444.
IARC, International Agency for Research on Cancer, 2002. WHO IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene. Fumonisin B1. IARC, Lyon, France, 82: 301-366.
JECFA, 2000. 53rd Meeting of the Joint FAO/WHO Expert Committee on Food Additives. http://www.inchem.org/documents/jecfa/jecmono/v44jec14.htm Accessed 13 April 2010.
JECFA, 2010. 72nd Meeting of the Joint FAO/WHO Expert Committee on Food Additives. http://www.who.int/entity/foodsafety/chem/summary72_rev.pdf Accessed 8 April 2010.
Luo X.Y., 1988. Outbreaks of moldy cereals poisoning in China. In: Issues in Food Safety, Toxicology Forum, Inc., Washington DC, USA, pp. 56-63.
Marasas W.F.O., Nelson P.E., 1987a. Hemorrhagic Syndrome. In: Mycotoxicology. Pennsylvania State University Press, University Park, PA, USA, pp. 41-44.
Marasas W.F.O., Nelson P.E., 1987b. Estrogenic Syndrome. In: Mycotoxicology. Pennsylvania State University Press, University Park, PA, USA, pp. 45-48.
Marasas W.F.O., et al., 2004. Fumonisins disrupt sphingolipid metabolism, folate transport, and neural tube development in embryo culture and in vivo: A potential risk factor for human neural tube defects among populations consuming fumonisin-contaminated maize. J. Nutrition 134: 711-716.
Maresca M., Fantini J., 2010. Some food-associated mycotoxins as potential risk factors in humans predisposed to chronic intestinal inflammatory diseases. Toxicon 56: 282-294.
Massart F., Meucci V., Saggese G., Soldani G., 2008. High growth rate of girls with precocious puberty exposed to estrogenic mycotoxins. J. Pediatr. 152: 690-695.
Merrill A.H. Jr., 1991. Cell regulation by sphingosine and more complex sphingolipids. J. Bioenergetics Biomembranes 23: 83-104.
Miller J.D., 1998. Global significance of mycotoxins. In: Mycotoxins and Phycotoxins – Developments in Chemistry, Toxicology and Food Safety, Miraglia, M., Van Egmond, H.P., Brera, C., Gilbert, J., (Eds.), Alaken, Fort Collins, CO, USA, pp. 3-15.
Missmer S.A., Suarez L., Felkner M., Wang E., Merrill,A.H. Jr., Rothman K.J., Hendricks K.A., 2006. Exposure to fumonisins and the occurrence of neural tube defects along the Texas-Mexico border. Environ. Health Perspect. 114:237-241.
Pascale M., Doko M.B., Visconti A., 1995. Determination of fumonisins in polenta by high performance liquid chromatography. In: Proceedings of the 2nd National Congress on Food Chemistry, GiardiniNaxos, 24-27 May 1995, La Grafica Editoriale, Messina, Italy, pp. 1067-1071.
Pestka J.J., 2008. Mechanisms of deoxynivalenol-induced gene expression and apoptosis. Food Addit. Contam. 25: 1128-140.
Rheeder J.P., Marasas W.F.O., Thiel P.G., Sydenham E.W., Shephard G.S., Schalkwyk D.J. van, 1992. Fusarium moniliforme and fumonisins in corn in relation to human esophageal cancer in Transkei. Phytopathology 82: 353-357.
Rheeder J.P., Marasas W.F.O., Vismer H.F., 2002. Production of fumonisin analogs by Fusarium species. Appl. Environ. Microbiol. 68: 2101-2105.
Saenz de Rodrigues C.A., Bongiovanni A.M., Conde de Borrego L., 1985. An epidemic of precocious development in Puerto Rican children. J. Pediatr. 107: 393-396.
Shephard G.S., Thiel P.G., Stockenström S., Sydenham E.W., 1996. Worldwide survey of fumonisin contamination of corn and corn-based products. J. AOAC Int. 79: 671-687.
Shephard G.S., Westhuizen L. van der , Gatyeni P.M., Katerere D.R., Marasas,W.F.O., 2005. Do fumonisin mycotoxins occur in wheat? J. Agric. Food Chem. 53: 9293-9296.
Shephard G.S., Marasas W.F.O., Burger H.-M., Somdyala N.I.M., Rheeder J.P., Westhuizen L. van der, Gatyeni P., Schalkwyk, D.J. van, 2007a. Exposure assessment for fumonisins in the former Transkei region of South Africa. Food Addit. Contam. 24: 621-629.
Shephard G.S., Westhuizen L. van der, Sewram V., 2007b. Biomarkers of exposure to fumonisin mycotoxins: A review. Food Addit. Contam. 24: 1196-1201.
Stevens V.L., Tang J., 1997. Fumonisin B1-induced sphingolipid depletion inhibits vitamin uptake via the glycosylphosphatidylinositol-anchored folate receptor. J. Biol. Chem. 272: 18020-18025.
Sun G., Wang S., Hu X., Su J., Huang T., Yu J., Tang L., Gao W., Wang J.-S., 2007. Fumonisin B1 contamination of home-grown corn in high-risk areas for esophageal and liver cancer in China. Food Addit. Contam. 24: 181-185.
Szuets P., Mesterhazy A., Falkay G., Bartok T., 1997. Early thelarche symptoms in children and their relations to zearalenone contamination in food stuffs. Cereal Res. Comm. 25: 429-436.
Turner P.C., BurleyV.J., Rothwell J.A., White K.L.M., Cade J.E., Wild C.P., 2008a. Deoxynivalenol: Rationale for development and application of a urinary biomarker. Food Addit. Contam. 25: 864-871.
Turner P.C., Rothwell J.A., White K.L.M., Gong Y., Cade J.E., Wild C.P., 2008b. Urinary deoxynivalenol is correlated with cereal intake in individuals from the United Kingdom. Environ. Health Perspect. 116: 21- 25.
Ueno Y., Iijima K., Wang S.D., Sugiura Y., Sekijima M., Tanaka T., Chen C., Yu S.Z., 1997. Fumonisins as a possible contributory risk factor for primary liver cancer; a 3-year study of corn harvested in Haimen, China by HPLC and ELISA. Food Chem. Toxicol. 35: 1143-1150.
Westhuizen L. van der, Shephard G.S., Scussel V.M., Costa L..L.F., Vismer H..F., Rheeder J.P., Marasas W.F.O., 2003. Fumonisin contamination and Fusarium incidence in corn from Santa Catarina, Brazil. J. Agric. Food Chem. 51: 5574-5578.
Westhuizen L. van der, Shephard G.S., Rheeder J.P., Burger H.-M., 2010. Individual fumonisin exposure and sphingoid base levels in rural populations consuming maize in South Africa. Food Chem. Toxicol. DOI: 10.1016/j.fct.2010.03.047.
Zhang H., Nagashima H., Goto T., 1997. Natural occurrence of mycotoxins in corn samples from high and low risk areas for human esophageal cancer in China. Mycotoxins 44: 29-35.
Zhang A., Cao J.-L., Yang B., Chen J.-H., Zhang Z.-T., Li S.-Y., Fu Q., Hugnes C.E., Caterson B., 2010. Effects of moniliformin and selenium on human articular cartilage metabolism and their potential relationships to the pathogenesis of Kashin-Beck disease. J. Zhejiang Univ. – Sci. B 11: 200-208. Google Scholar
Shephard, G. S. . (2011). Fusarium mycotoxins and human health. Review. Plant Breeding and Seed Science, 64, 113–122. Retrieved from http://ojs.ihar.edu.pl/index.php/pbss/article/view/348
Authors
Gordon S. Shephardgordon.shephard@mrc.ac.za
PROMEC Unit, Medical Research Council, PO Box 19070, Tygerberg 7505, South Africa South Africa
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