178 naturaltoxins: risk, regulations, analysis and ... · eu feed limits exist for aflatoxins eu...

Hans van Egmond, 7 December 2010

Natural toxins:Risks, regulations, analysis

and international co-operation

Natural ToxinsNatural Toxins

mycotoxinsmycotoxins

bacterial toxinsbacterial toxins

mycotoxinsmycotoxins

Natural ToxinsNatural Toxins

bacterial toxinsbacterial toxins

bacterial toxinsbacterial toxins

phycotoxinsphycotoxins

mycotoxinsmycotoxins

Natural ToxinsNatural Toxins

phycotoxinsphycotoxins

bacterial toxinsbacterial toxins plant toxinsplant toxins

phycotoxinsphycotoxins

mycotoxinsmycotoxins

Natural ToxinsNatural Toxins

plant toxinsplant toxins

bacterial toxinsbacterial toxins

animal toxinsanimal toxins

plant toxinsplant toxins

phycotoxinsphycotoxins

mycotoxinsmycotoxins

Natural ToxinsNatural Toxins

animal toxinsanimal toxins

bacterial toxinsbacterial toxins

animal toxinsanimal toxins

plant toxinsplant toxins

phycotoxinsphycotoxins

mycotoxinsmycotoxins

Natural ToxinsNatural Toxins

� Introduction� Mycotoxins - a continuous issue

� Phycotoxins - interesting developments� Plant toxins - becoming of growing concern

� International cooperation� Summary

Outline of presentation

� Introduction� Mycotoxins - a continuous issue

� Phycotoxins - interesting developments� Plant toxins - becoming of growing concern

� International cooperation� Summary

Outline of presentation

Mycotoxins:� Naturally occurring chemical compounds produced

by fungi, with adverse effects to man and animals

� Various toxic effects described in man and animals

Toxic effects of mycotoxins

hepatotoxic

immunotoxic

nephrotoxic

neurotoxic

oestrogenic

teratogenic

OTA PAT FUM ZEATCT

carcinogenic

AFL

Mycotoxins:� Naturally occurring chemical compounds produced

by fungi, with adverse effects to man and animals

� Various toxic effects described in man and animals

� Metabolites of mycotoxins also named “mycotoxins”

� Important producing fungi: Aspergillus, Penicillium and Fusarium; hundreds of mycotoxins known

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

Human aflatoxicosis in Kenya, 2004

Photo: courtesy Henry Njapau and Masja Straetemans

� Village-grown maize suspectedto play a causal role

� FDA emergency team confirmed hypothesis of human aflatoxicosis

� New outbreaks occurred in 2005, 2006 and now again in 2010

Human aflatoxicosis in Kenya, 2004

Photo: courtesy Henry Njapau and Masja Straetemans

Rapid Alert System for Food and Feed

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

� Allows MS to identify potential problems and take measures

� In 2009: 665 mycotoxin issues

RASFF 2009: Border rejection notifications

Border Rejection notifications 2009Rest46%

Veterinary medicine products

4%

Pathogenic micro-

organisms7% Food

additives4%

Compositions3%

Mycotoxins36%

EFSA and JECFA: risk assessments

� JECFA: Joint FAO/WHO Expert Committee on Food Additives

� Risk assessments of variousmycotoxins performed

� Published for AFL, OTA, ZEA,PAT, FUM, DON, T-2/HT-2

� EFSA: risk assessments done for feed, ongoing for food (e.g. various trichothecenes,ergot alkaloids, Alternaria toxins)

� Worldwide inquiries:1981, 1987, 1995 & 2003, resulting in various publications

� Inquiry 2003 published as FAO FNP 81 (2004)

� Chinese, French and Spanish translations available

Inquiries on mycotoxin regulations

Mycotoxin regulatory situation in Europe

� 39 nations with known regulations � EU food limits exist for AFLAs,

OTA, PAT, ZEA, DON and FUM� EU food limits discussed for

T-2/HT-2 toxins and ergot alkaloids� The near future: Alternaria toxins

and several other mycotoxins� EU feed limits exist for aflatoxins� EU feed guidance limits established

for OTA and Fusarium mycotoxins

Analytical methodology for mycotoxins

� US based, international involvement

� Development and validation of methods of analysis and improvement of AQA

� Approx. 45 mycotoxin methods in “OMA”

� European equivalent of ISO� Performance criteria approach, usually

based on interlaboratory studies� 12 mycotoxin methods standardized� EU interlaboratory studied methods CEN

AOAC and CEN mycotoxin methods

� TLC: veteran technique, powerful and cheap� HPLC: frequently used and extensively

validated, often in combination with IA cleanup

� ELISA: especially useful for rapid screening

Newer developments in methodology

� LC-MS and GC-MS� Biosensors� Capillary Zone Electrophoresis� Infrared techniques� Acoustic methods� Molecular Imprinted Polymers� Fluorescence Polarisation Immunoassay� Dip Stick Immunoassay� Transcriptomics

� Introduction� Mycotoxins - a continuous issue

� Phycotoxins - interesting developments� Plant toxins - becoming of growing concern

� International cooperation� Summary

Outline of presentation

“Red tides” - explosive growth of algae

Dinoflagellates, small toxin-producers

Dinophysis acuminata

Pyrodinium bahamense

Groups of marine biotoxins

� “Paralytic shellfish poisoning” toxins (PSP)� “Diarrhoeic shellfish poisoning” toxins (DSP)

� Azaspiracids (AZA)� “Amnesic shellfish poisoning” toxins (ASP)� Emerging: palytoxins,

brevetoxins, cyclic imines

� Ciguatera toxins

The EU situation on phycotoxins

� Several toxin groups regulated(OA, AZA, YTX, PTX, STX, DA)

� Rodent assays will soon be banned

� EFSA suggests more stringent limits for various regulated toxins; emerging toxins discussed

� Interesting chemical alternatives to MBA explored

� Networks exist (CEN, CRL/NRL), and someprojects: BioCop, MoniQA, CONffIDENCE

Consequences of climate change

� Expected increase of algal blooms � More, more frequent and more types of marine

biotoxins in fishery products (“emerging toxins”)� Example: ciguatera toxins now found in

Madeira and the Canary islands (Europe)� Governments to take adequate measures for

risk management� Governments to be encouraged to carry out

integral monitoring (algae and shellfish) to protect the consumer

Research needs

� Improve systems to predict harmful algalblooms for risk management

� Prediction of algal blooms: knowledgerequired about modelling and ecology

� Shift research from local to global scale tobetter understand the impact of climate change

� The increased chance of occurrence ofmarine biotoxins requires more knowledgeof toxicology and analytical possibilities

� Introduction� Mycotoxins - a continuous issue

� Phycotoxins - interesting developments� Plant toxins - becoming of growing concern

� International cooperation� Summary

Outline of presentation

Plant toxins: growing concern

� Recurring incidents, sometimes very serious

� Regulations for food and feed scarce� Increased interest in the EU, e.g. for alkaloids� EFSA opinions: focus on validation of analytical

methods, development of RMs and surveys � Data to be produced on carry-over � Limited project activities exist (CONffIDENCE)

Outbreak of liver disease in Hirat district

Outbreak of liver disease in Hirat district

� More than 270 people affected

� Approx. 50 people died

� WHO alarmed, and RIVMcontracted to investigatethe cause of the disease

� Hypothesis: PA poisoning

� Samples sent to RIVM

� PA poisoning confirmed

Pilot carry-over study ragwort

� Introduction� Mycotoxins - a continuous issue

� Phycotoxins - interesting developments� Plant toxins - becoming of growing concern

� International cooperation� Summary

Outline of presentation

Examples of European collaboration

� Many networks and activities ongoing

� Rapid Alert System for Food and Feed

� EFSA: scientific opinions (risk assessments)

� CEN: the European equivalent of ISO

� EU-RLs for mycotoxins and marine biotoxins

� European research and networking projects

Examples of European collaboration

� Many networks and activities ongoing

� Rapid Alert System for Food and Feed

� EFSA: scientific opinions (risk assessments)

� CEN: the European equivalent of ISO

� EU-RLs for mycotoxins and marine biotoxins

� European research and networking projects

NRL networks on mycotoxins and marine biotoxins

27 NRLs

1 EU-RL

>> RFLs

EC

Tasks of the EU-RL

27 NRLs

1 EU-RL

>> RFLs

EC

� Provide NRLs with methods

� Coordinate comparative testing

� Organise training courses

� Technical assistance to the Commission

� Collaborate with labs in third countries

Examples of European collaboration

� Many networks and activities ongoing

� Rapid Alert System for Food and Feed

� EFSA: scientific opinions (risk assessments)

� CEN: the European equivalent of ISO

� EU-RLs for mycotoxins and marine biotoxins

� European research and networking projects

� IP Food Quality & Safety, 2005-2010 (just ended)

� Biotech-based methods explored and exploited� Includes WPs on mycotoxins and phycotoxins

� Involves various analytical techniques(such as sensors, transcriptomics)

� Continuation in national projects & interaction with MoniQA is foreseen (validation studies)

MoniQAMoniQA

� NoE Food Quality & Safety, 2007-2012

� Focus on validation of and performance criteriafor methods to monitor food hazards

� Includes activities on different groups of analytes

� Emphasis on rapid and high throughput methods� Active WG on mycotoxins/phycotoxins

� Mycotoxin workshops and interlaboratory studies form part of the activities

� LCP Food, Agriculture and Fisheries, and Biotechnology, 2008-2012

� Simple, fast, multi-analyte, multi-class detection � Includes WP Biotoxins

- alkaloids (pyrrolizidine, tropane, ergot)- Fusarium mycotoxins (TCT, ZEA, FUM)- Various types of phycotoxins (PSP, DSP, ASP)

� Training workshops and educating modules� Interaction with MoniQA (validation studies)

� LCP Food, Agriculture and Fisheries, and Biotechnology, 2009-2013

� “Reduction of mycotoxins in food and feed chains”� Focus on AFL, OTA, TCT, ZEA en FUM � Rapid methods (strips, LFD, multimycotoxin tests)� Analytical WP: service to other work packages � Organisation of (training) workshops and

conferences (Europe, Asia, Africa, Latin America)

� Introduction� Mycotoxins - a continuous issue

� Phycotoxins - interesting developments� Plant toxins - becoming of growing concern

� International cooperation� Summary

Outline of presentation

Summary and conclusions

� Natural toxins: a worldwide concern� Mycotoxins: many regulations, analytical

situation advanced, strong networks� Phycotoxins: regulations need revision,

analytical progress, networks growing � Plant toxins: regulations scarce, analytically

least advanced, networks to be formed� Climate change will affect natural toxins� Several international activities ongoing

to cope with the problems of natural toxins

Thank you for listening !

Natural toxins:Risks, regulations, analysis

and international co-operation

Consequences of climate change

� Expected changes in range of latitudes, where certain fungi are able to compete

� Example: F. graminearum growth: NIV increase� Drought, flooding and other consequences of

climate change may result in more mycotoxinsand changed toxin profiles

� Example: aflatoxins found in Italy since 2003,and in other parts of Central Europe

� Response of insects and plant diseases to climate change poorly understood, but increases expected

Research needs

� Better understanding of precise impact of climate change on insects and other pests

� Investigate consequences on soil characteristics: very relevant for fungal infestation

� Stimulate research from local to global scale tobetter understand the impact of climate change

� EMTOX project: one of the objectives: Quantify relationship between climate change and toxins

� Monitoring of mycotoxin occurrence, to observe possible changes in toxin profiles and levels

Various translations of FNP 81 available

� Succesful carry-over experiment� Various PA found in milk, jacoline major

compound (transfer: 6-8 % of ingested amount)� Risk assessment by RIVM: allowed daily weed

intake of cow: 0.66 g/day� EU - workshop on PA held, February 2010� Second carry-over study ongoing� EFSA: opinions requested for various alkaloids

and possibly other plant toxins in food

Early conclusions and follow-up