MYCO-GLOBE MEETINGStanhope Hotel, Brussels, Belgium
October 21 – 22, 2004
MYCOTOXINS:A GLOBAL PROBLEM
WFO MARASASPROMEC UNIT, MEDICAL RESEARCH COUNCIL
TYGERBERG, SOUTH AFRICA
MOST IMPORTANT MYCOTOXIN-PRODUCING
FUNGI
Aspergillus flavusAspergillus ochraceusPenicillium verrucosumFusarium graminearumFusarium verticillioides
MOST IMPORTANTNATURALLY OCCURRING
MYCOTOXINS
AflatoxinOchratoxin
DeoxynivalenolZearalenoneFumonisin
MYCOTOXICOSES OF ANIMALS CAUSED BY
MYCOTOXINS IN FEEDS
Aflatoxicosis – AflatoxinNephropathy – Ochratoxin
Feed Refusal Syndrome – DeoxynivalenolHyperoestrogenism – Zearalenone
Pulmonary Oedema Syndrome – FumonisinLeukoencephalomalacia – Fumonisin
HUMAN DISEASESASSOCIATED WITH
MYCOTOXINS IN FOOD
AflatoxinAcute Toxic Hepatitis
Liver CancerFumonisin
Esophageal CancerNeural Tube Defects
AFLATOXIN B1
O O
O
O O
OCH3
H
H
LIVER CANCER IN MOZAMBIQUE
MTL’S OF AFLATOXININ SOME COUNTRIES
Country Foods MTL (ppb)Total Afla AFB1
Data from FAO (1997)
China Groundnuts and Maize 20 -Rice 10Wheat 5 -
Germany All Foods 4 2Japan All Foods - 10South Africa All Foods 10 5USA All Foods 20 -
Fumonisin B1 : X = OH, Y = OH
Fumonisin B2 : X = OH, Y = H
Fumonisin B3 : X = H, Y = OH
H 3C
CH3 CH3
CH3
NH 2
OH
35101216
O
OR
OR
R =
Y
X
COOH
COOH
14
21 22
tricarballylic acid (TCA)
STEREOCHEMISTRY OFB SERIES FUMONISINS
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
Fumonisin inhibits folate uptakeand causes neural tube defectsin mice and possibly in humans
NEURAL TUBE DEFECTS
Corn Products MTL (ppm)Total Fumonisins
Dry milled corn products< 2.25% fat 2> 2.25% fat 4
Cleaned corn - popcorn 3
FDA GUIDANCE FOR INDUSTRYFUMONISIN LEVELS IN HUMAN FOODS
Data from FDA (2001)
FDA GUIDANCE FOR INDUSTRYFUMONISIN LEVELS IN ANIMAL FEEDS
Feeds MTL (ppm)Total Fumonisins
Horses and Rabbits 1Pigs and Catfish 10Breeding Ruminants and Poultry 15Ruminants for slaughter 30Poultry for slaughter 50Data from FDA (2001)
g/70 kg bw/day
South Africa - Rural 460
South Africa - Urban 270
Europe 7
CORN INTAKE PROFILES
PDI AND TDI (µg/kg/day)OF FUMONISINS IN CORN
PDI TDINOEL/1000 JECFA
South Africa - Rural 47-355 0.8 2.0South Africa - Urban 1.2 0.8 2.0Europe 0.1 0.8 2.0
66.633.325.016.78.31.71040
16.713.310.06.73.31.70.7200
803020102.012
33.412.58.34.20.8526.610.06.73.30.7420.07.55.02.50.5313.45.03.31.70.326.62.51.70.80.213.41.30.80.40.10.51.40.50.30.200.24001501005010FB (ppm)
PMTDI = 2 µg/kg bw/day (nephrotoxicity)PMTDI = 0.8 µg/kg bw/day (carcinogenicity)
CORN INTAKE [g/person (60kg)/day]FB
INTA
KE (µg/kg bw
/day)
IMPACT OF LOWER EUAFLATOXIN STANDARDSON AFRICAN EXPORTS
Number of cancer deaths saved~2 per billion people
Loss in African exports of groundnuts and cerealsUS $ 670 million
Data from Otsuki et al (2001)
“A World Bank study has calculated that theEuropean Union regulation on aflatoxin costs
Africa $670 million each year in exports ofcereals, dried fruit and nuts.And what does it achieve?
It may possibly save the life of one citizen ofthe European Union every two years........
Surely a more reasonable balance can be found”
COMMENT BY KOFI ANNAN Secretary-General, United Nations
66.633.325.016.78.31.71040
16.713.310.06.73.31.70.7200
803020102.012
33.412.58.34.20.8526.610.06.73.30.7420.07.55.02.50.5313.45.03.31.70.326.62.51.70.80.213.41.30.80.40.10.51.40.50.30.200.24001501005010FB (ppm)
PMTDI = 2 µg/kg bw/day (nephrotoxicity)PMTDI = 0.8 µg/kg bw/day (carcinogenicity)
CORN INTAKE [g/person (60kg)/day]FB
INTA
KE (µg/kg bw
/day)
“Genetic engineering approaches are the mostattractive methods now under development,and the future of fumonisin reduction may
very well lie in the hands of these researchers”Munkvold & Desjardins (1997)
BIOTECHNOLOGY SOLUTIONS
“The 21st 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 CROPSReducing infection by the fungusDegrading the mycotoxin in plantaDisrupting mycotoxin biosynthesisInducing insect resistance
Transgenic corn with the Bt genefor insect resistance is a
promising solution to the fumonisin problembecause of the close association
between European corn borer infestation andFusarium verticillioides infection in corn
Bt CORN HYBRIDS
Significantly lower levels of fumonisin have been foundin Bt compared to conventional corn hybrids
0
5
10
15
20
25TO
TAL
FUM
ON
ISIN
S (p
pm)
CBH351 BT11 MON810 CBH351 BT11 MON810
MAIZE LINES
Standard maize Bt-maize
Natural ECB infestation Manual ECB infestation
* ** * *
= P<0.05*Data from Munkvold et al., 1997
REDUCTION OF FUMONISINS IN Bt CORN
CONCLUSIONS
The ultimate solution tothe global mycotoxin problem
is not regulation, butreduction of fungal infection
and mycotoxin levels incrop plants in the field and in storage
contd…..
CONCLUSIONSImplementation of the Code of Practice of the Codex Alimentarius Commission for
the reduction of mycotoxins in cereal grainsshould reduce the risk of people who are
not protected by traditional risk assessment
Novel strategies need to be developed such as the reduction of fumonisin levels in genetically modified
Bt corn and improved risk communicationto inform rural communities aboutthe 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 fundingfrom 1975 to the present