MYCO-GLOBE MEETING Stanhope Hotel, Brussels, Belgium October 21 22, 2004
MYCOTOXINS: A GLOBAL PROBLEM WFO MARASAS PROMEC UNIT, MEDICAL RESEARCH COUNCIL TYGERBERG, SOUTH AFRICA wally.marasas@mrc.ac.za
MOST IMPORTANT MYCOTOXIN-PRODUCING FUNGI Aspergillus flavus Aspergillus ochraceus Penicillium verrucosum Fusarium graminearum Fusarium verticillioides
MOST IMPORTANT NATURALLY OCCURRING MYCOTOXINS Aflatoxin Ochratoxin Deoxynivalenol Zearalenone Fumonisin
MYCOTOXICOSES OF ANIMALS CAUSED BY MYCOTOXINS IN FEEDS Aflatoxicosis Aflatoxin Nephropathy Ochratoxin Feed Refusal Syndrome Deoxynivalenol Hyperoestrogenism Zearalenone Pulmonary Oedema Syndrome Fumonisin Leukoencephalomalacia Fumonisin
HUMAN DISEASES ASSOCIATED WITH MYCOTOXINS IN FOOD Aflatoxin Acute Toxic Hepatitis Liver Cancer Fumonisin Esophageal Cancer Neural Tube Defects
AFLATOXIN B 1 O O H O O O OCH 3 H
LIVER CANCER IN MOZAMBIQUE
MTL S OF AFLATOXIN IN SOME COUNTRIES Country Foods MTL (ppb) Total Afla AFB 1 China Groundnuts and Maize 20 - Rice 10 Wheat 5 - Germany All Foods 4 2 Japan All Foods - 10 South Africa All Foods 10 5 USA All Foods 20 - Data from FAO (1997)
STEREOCHEMISTRY OF B SERIES FUMONISINS 21 22 CH 3 OR CH 3 Y NH 2 H 3 C 16 14 12 10 5 3 CH 3 OR X OH O COOH Fumonisin B 1 : X = OH, Y = OH Fumonisin B 2 : X = OH, Y = H Fumonisin B 3 : X = H, Y = OH R = tricarballylic acid (TCA) COOH
MOLDY CORN EARS INFECTED BY FUSARIUM
EQUINE LEUKOENCEPHALOMALACIA
PORCINE PULMONARY EDEMA
LIVER CANCER IN A RAT
ESOPHAGEAL CANCER Fumonisin in home-grown corn is associated with human esophageal cancer in Transkei, South Africa and LinXian, China
TRANSKEI REGION, SOUTH AFRICA
CORN STORAGE CRIBS IN TRANSKEI
MOLDY CORN EARS INFECTED BY FUSARIUM
NEURAL TUBE DEFECTS Fumonisin inhibits folate uptake and causes neural tube defects in mice and possibly in humans
FDA GUIDANCE FOR INDUSTRY FUMONISIN LEVELS IN HUMAN FOODS Corn Products MTL (ppm) Total Fumonisins Dry milled corn products < 2.25% fat 2 > 2.25% fat 4 Cleaned corn - popcorn 3 Data from FDA (2001)
FDA GUIDANCE FOR INDUSTRY FUMONISIN LEVELS IN ANIMAL FEEDS Feeds MTL (ppm) Total Fumonisins Horses and Rabbits 1 Pigs and Catfish 10 Breeding Ruminants and Poultry 15 Ruminants for slaughter 30 Poultry for slaughter 50 Data from FDA (2001)
CORN INTAKE PROFILES g/70 kg bw/day South Africa - Rural 460 South Africa - Urban 270 Europe 7
PDI AND TDI (µg/kg/day) OF FUMONISINS IN CORN PDI TDI NOEL/1000 JECFA South Africa - Rural 47-355 0.8 2.0 South Africa - Urban 1.2 0.8 2.0 Europe 0.1 0.8 2.0
CORN INTAKE [g/person (60kg)/day] PMTDI = 2 µg/kg bw/day (nephrotoxicity) PMTDI = 0.8 µg/kg bw/day (carcinogenicity) FB (ppm) 10 50 100 150 200 400 0.2 0.5 1 2 3 4 5 10 12 0 0.1 0.2 0.3 0.5 0.7 0.8 1.7 2.0 0.2 0.4 0.8 1.7 2.5 3.3 4.2 8.3 10 0.3 0.8 1.7 3.3 5.0 6.7 8.3 16.7 20 0.5 1.3 2.5 5.0 7.5 10.0 12.5 25.0 30 0.7 1.7 3.3 6.7 10.0 13.3 16.7 33.3 40 1.4 3.4 6.6 13.4 20.0 26.6 33.4 66.6 80 FB INTAKE (µg/kg bw/day)
IMPACT OF LOWER EU AFLATOXIN STANDARDS ON AFRICAN EXPORTS Number of cancer deaths saved ~2 per billion people Loss in African exports of groundnuts and cereals US $ 670 million Data from Otsuki et al (2001)
COMMENT BY KOFI ANNAN Secretary-General, United Nations A World Bank study has calculated that the European Union regulation on aflatoxin costs Africa $670 million each year in exports of cereals, dried fruit and nuts. And what does it achieve? It may possibly save the life of one citizen of the European Union every two years... Surely a more reasonable balance can be found
CORN INTAKE [g/person (60kg)/day] PMTDI = 2 µg/kg bw/day (nephrotoxicity) PMTDI = 0.8 µg/kg bw/day (carcinogenicity) FB (ppm) 10 50 100 150 200 400 0.2 0.5 1 2 3 4 5 10 12 0 0.1 0.2 0.3 0.5 0.7 0.8 1.7 2.0 0.2 0.4 0.8 1.7 2.5 3.3 4.2 8.3 10 0.3 0.8 1.7 3.3 5.0 6.7 8.3 16.7 20 0.5 1.3 2.5 5.0 7.5 10.0 12.5 25.0 30 0.7 1.7 3.3 6.7 10.0 13.3 16.7 33.3 40 1.4 3.4 6.6 13.4 20.0 26.6 33.4 66.6 80 FB INTAKE (µg/kg bw/day)
BIOTECHNOLOGY SOLUTIONS Genetic engineering approaches are the most attractive methods now under development, and the future of fumonisin reduction may very well lie in the hands of these researchers Munkvold & Desjardins (1997) The 21 st Century will be biological and diverse, with biotechnology being the kingpin of the process Olusegun Obasanjo - President of Nigeria
TRANSGENIC STRATEGIES TO REDUCE MYCOTOXINS IN CROPS Reducing infection by the fungus Degrading the mycotoxin in planta Disrupting mycotoxin biosynthesis Inducing insect resistance
Bt CORN HYBRIDS Transgenic corn with the Bt gene for insect resistance is a promising solution to the fumonisin problem because of the close association between European corn borer infestation and Fusarium verticillioides infection in corn
Significantly lower levels of fumonisin have been found in Bt compared to conventional corn hybrids
REDUCTION OF FUMONISINS IN Bt CORN 25 TOTAL FUMONISINS (ppm) 20 15 10 5 0 Natural ECB infestation Manual ECB infestation * * * * * CBH351 BT11 MON810 CBH351 BT11 MON810 MAIZE LINES Standard maize Bt-maize * = P<0.05 Data from Munkvold et al., 1997
CONCLUSIONS The ultimate solution to the global mycotoxin problem is not regulation, but reduction of fungal infection and mycotoxin levels in crop plants in the field and in storage contd..
CONCLUSIONS Implementation of the Code of Practice of the Codex Alimentarius Commission for the reduction of mycotoxins in cereal grains should reduce the risk of people who are not protected by traditional risk assessment Novel strategies need to be developed such as the eduction of fumonisin levels in genetically modified Bt corn and improved risk communication to inform rural communities about the health hazard of mycotoxins
ACKNOWLEDGEMENTS All my colleagues, past and present, at the PROMEC Unit of the South African Medical Research Council (MRC) for their invaluable contributions to the global knowledge about mycotoxins The MRC for continuous funding from 1975 to the present