MYCO-GLOBE MEETINGStanhope Hotel, Brussels, Belgium

October 21 – 22, 2004

MYCOTOXINS:A GLOBAL PROBLEM

WFO MARASASPROMEC UNIT, MEDICAL RESEARCH COUNCIL

TYGERBERG, SOUTH AFRICA

wally.marasas@mrc.ac.za

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