1SELAMAT open seminar, 25th June 2008

Aflatoxins: risks, regulations and limits

Hans van Egmond, RIVM

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Half a century ago... Turkey-X disease:the discovery of aflatoxins

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Turkey-X: Quotationsfrom the correspondence

• “We are fairly certain that this ‘toxic factor’ in groundnuts is not a new problem”

• “We do not know the chemical composition of the‘toxic factor’, but the source of toxicity is likely relatedto fungal contamination at a stage before processing”

• “We think the whole problem is serious from a human and animal health point of view and from economic aspects”

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• Introduction• Effects and occurrence of aflatoxins • The EU’s RASFF system: focus on aflatoxins• Risk assessment of aflatoxins • The process of setting regulations for aflatoxins• Worldwide limits for aflatoxins • Summary

Outline of presentation

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• Introduction• Effects and occurrence of aflatoxins• The EU’s RASFF system: focus on aflatoxins• Risk assessment of aflatoxins• The process of setting regulations for aflatoxins• Worldwide limits for aflatoxins • Summary

Outline of presentation

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aflatoxin B1 aflatoxin M1

Chemical structures of aflatoxins B1 and M1

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Effects aflatoxin B1

• Strong acute toxin in various experimental animals• Potent liver carcinogen in various experimental animals• Possible role in human liver cancer in Asia and Africa• Possible role in kwashiorkor• Stunted growth in children• Kenya 2004, 2005: outbreak of aflatoxicosis

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317 people in Kenyan villages got ill; 127 died,including many children

The Kenya outbreak of aflatoxicosis, 2004

Photo: courtesy Henry Njapauand Masja Straetemans

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• Village-grown maize suspected to play acausal role

• FDA emergency teamconfirmed hypothesis of human aflatoxicosis

• New outbreak occurred in 2005

Kenya aflatoxicosis, 2004

Photo: courtesy Henry Njapauand Masja Straetemans

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Aflatoxins: pre- and post- harvest problems

• Produced primarily by strains of Aspergillus flavus,A. parasiticus and A. nomius

• A. flavus: more adapted to aerial parts of plants (leaves, flowers), dominant on maize, cotton seed, tree nuts (aflatoxins B1, B2)

• A. parasiticus: well adapted to a soil environment, prominent on peanuts (aflatoxins B1, B2, G1 and G2)

• A. nomius: found on various cereals and nuts, e.g. producer of B and G aflatoxins in Brazil nuts

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Aflatoxin M1: the milk-aflatoxin

• Approx. 1-6 % of the aflatoxin B1 in animal feedstuffs is transferred to aflatoxin M1 in milk

• A seasonal trend is noted in many surveys, with lower levels occurring in summer months

• The toxin is found in human breast milk, sometimes at rather high levels in samples from tropical and subtropical regions

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• Introduction• Effects and occurrence of aflatoxins • The EU’s RASFF system: focus on aflatoxins• Risk assessment of aflatoxins• The process of setting regulations for aflatoxins• Worldwide limits for aflatoxins • Summary

Outline of presentation

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RASFF in the EU

• Quick information-exchange in the EU on risks to human health

• Allows MS to identify potential problems and take measures

• In 2006: near to 900 mycotoxin issues

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RASFF 2006: information notifications

Information notifications 2006

Rest37%

Veterinary medicine products

4%

Pathogenic micro-

organisms7%

Food additives

8%

Compositions4%

Mycotoxins40%

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cereal(s) coffee & baby fruits & herbs & fruit nuts & products cocoa food veg. spices juices products

Mycotoxin Notifications [RASFF 2006]

fumonisins

patulin

ochratoxin A

aflatoxins 5 1 69 37 684

14 1

11 12 27 4

1 1 5

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• Introduction• Effects and occurrence of aflatoxins • The EU’s RASFF system: focus on aflatoxins• Risk assessment of aflatoxins • The process of setting regulations for aflatoxins• Worldwide limits for aflatoxins • Summary

Outline of presentation

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International bodies involvedin assessing risks on aflatoxins

• IARC: International Agency for Research on Cancer- Classified aflatoxins as group I: known human carcinogens

• JECFA: Joint FAO/WHO Expert Committeeon Food Additives

- Assessment of carcinogenic potency of aflatoxin B1

• EFSA: European Food Safety Authority- Opinion on the potential increase of risk by a possible increase of maximum levels for aflatoxins in tree nuts

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International bodies involvedin assessing risks on aflatoxins

• IARC: International Agency for Research on Cancer- Classified aflatoxins as group I: known human carcinogens

• JECFA: Joint FAO/WHO Expert Committeeon Food Additives

- Assessment of carcinogenic potency of aflatoxin B1

• EFSA: European Food Safety Authority- Opinion on the potential increase of risk by a possible increase of maximum levels for aflatoxins in tree nuts

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JECFA: safety evaluation of mycotoxins

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Risk assessment process

• Hazard identification – Use of all data to establish that a compound has the capacity to cause an adverse effect

• Hazard characterization – Assessment of the relationship between dose, and the incidence or severity of an effect

• Exposure assessment – Estimation of the dose, to which various individuals or populations, are exposed

• Risk characterization – Estimation of the incidence and severity of the adverse effects that are liable to occur ina population due to actual or predicted exposure

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Contaminants without identifiedthresholds of toxicity (e.g. aflatoxins)

• The ideal way to evaluate substances withoutidentified thresholds: quantitative risk assessment

• Difficult with most contaminants because sufficientdose-response data are lacking

• Aflatoxins were the first carcinogenic contaminants evaluated by JECFA

• The Committee advised Codex Alimentarius that theybe present in the food supply at ‘irreducible levels’

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Risk assessment versus risk management

• Codex did not find ‘irreducible level’ (ALARA) to be a useful endpoint for risk management:- difficult to manage: health effects are not quantified- creates difficulty: widely varying levels around the world

• JECFA re-evaluated aflatoxins: calculation of population risks, based on hypothetical standards:

-10 µg AFB1/kg groundnuts or maizeor

- 20 µg AFB1/kg groundnuts or maize

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Lower-risk group – population risks(no HBV prevalent)

• 20 µg/kg standard- 0.0041 cancers per year per 100 000 people

• 10 µg/kg standard- 0.0039 cancers per year per 100 000 people

• Reducing the hypothetical standard from 20 to 10 µg/kg yields a reduction in estimated population risk by 2 cancers per year per billion people

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Higher-risk group – population risks(HBV prevalent)

• 20 µg/kg standard- 0.17 cancers per year per 100 000 people

• 10 µg/kg standard- 0.14 cancers per year per 100 000 people

• Reducing the hypothetical standard from 20 to 10 µg/kg yields a reduction in estimated population risk by 300 cancers per year per billion people

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Aflatoxin conclusions

• Establishment of a standard is more important thanits actual level, because a majority of the risk is borne by those consuming highly contaminated product

• Reduction in AFB1 intake in populations with a high incidence of hepatitis B will result in a greater reduction in liver cancer than reduction of the AFB1intake in populations with low incidence of hepatitis B

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• Introduction• Effects and occurrence of aflatoxins • The EU’s RASFF system: focus on aflatoxins• Risk assessment of aflatoxins by JECFA• The process of setting regulations for aflatoxins• Worldwide limits for aflatoxins • Summary

Outline of presentation

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toxicity data, survey analytical data, methods of sampling

and analysis

trade contacts with other countries, sufficiency of

food supply

Factors influencing regulations

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The mycotoxin regulatory puzzle

TOXICITY

OCCURRENCE

TRADE

ANALYSIS

SAMPLING FOOD SUPPLY

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Weighing the various factors: not trivial

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International inquiry 2003

• Inquiry 2003: FAO-contracted activity of RIVM• Information: Dutch Embassies and personal contacts • Details asked a.o. about tolerance limits, legal bases,

responsible authorities, methods of sampling and analysis• Results: regulations exist in 100 countries and for 13 toxins• FAO FNP 81: recently published in 4 different languages

Questionnaire February 2003For an Update of

“Worldwide regulations for mycotoxins 1995”FAO Food and Nutrition Paper 64

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Various translations of FNP 81 available

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• Introduction• Effects and occurrence of aflatoxins • The EU’s RASFF system: focus on aflatoxins• Risk assessment of aflatoxins by JECFA• The process of setting regulations for aflatoxins• Worldwide limits for aflatoxins• Summary

Outline of presentation

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Ranges and typical limitsfor total aflatoxins in food

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0 5 10 15 20 25 30 35 40 45 50

µg/kg

North Am erica 2003

Latin Am erica 2003

Europe 2003

Asia/Oceania 2003

Africa 2003

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Aflatoxin B1 in food

1

29

21

5

2

3

1 µg/kg

2 µg/kg

5 µg/kg

10 µg/kg

15 µg/kg

20 µg/kg

number of countries

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Total aflatoxins in food

1

1

1

28

2

7

8

18

7

2

0 µg/kg

1 µg/kg

3 µg/kg

4 µg/kg

5 µg/kg

10 µg/kg

15 µg/kg

20 µg/kg

30 µg/kg

35 µg/kg

number of countries

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Aflatoxin M1 in milk

1

34

1

22

1

1

not detectable

0.05 µg/kg

0.2 µg/kg

0.5 µg/kg

5 µg/kg

15 µg/kg

number of countries

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Aflatoxin B1 in feed for dairy cattle

27

5

1

3

1

2

5 µg/kg

10 µg/kg

15 µg/kg

20 µg/kg

25 µg/kg

50 µg/kg

number of countries

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Summary

• Aflatoxins: significant adverse effects on humans • RASFF notifications: largely caused by aflatoxins• Reduction of HBV prevalence will result in significant

reduction of liver cancer due to aflatoxins• Many factors involved in setting aflatoxin regulations• Worldwide limits for aflatoxins vary widely• Finally......................

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Half a century ago... a young boy and his sister in Jambi, Sumatra

40SELAMAT open seminar, 25th June 2008

Aflatoxins: risks, regulations and limits

Hans van Egmond, RIVM

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Terima Kasih !