The work of EFSA’s Panel on Contaminants in the Food Chain

(CONTAM)Food Safety Authority of Ireland Seminar on Contaminants

Dublin 17 November 2009

Claudia Heppner, Head of the CONTAM unit

Outline of presentation

• EFSA´s mission• CONTAM Panel• Overview of CONTAM scientific outputs• Some examples of CONTAM outputs• Some examples of follow up of risk assessments• Current and future work programme of the

CONTAM Panel

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EFSA's mission

• EFSA is the European Union's scientific risk assessment body for food and feed safety, providing the scientific basis for risk management decisions in this area (Regulation (EC) 178/2002).

• Provide scientific and technical advice on all matters within these fields.

• Communicate all scientific outputs publicly (communication task is shared with EC/MS).

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EFSA tasking

European Commission

European Parliament

Member States

EFSA (“self mandate”)

Question?

Risk Assessment

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How does EFSA work?

• Food additives and nutrient sources (ANS)

• Food contact materials, enzymes, flavourings (CEF)

• Feed additives (FEEDAP) • Genetically modified

organisms (GMO)• Nutrition (NDA)

• Animal health and welfare (AHAW)

• Biological hazards (BIOHAZ)

• Contaminants (CONTAM)• Plant health (PLH)• Plant protection products

(PPR) • Scientific Committee (SC)

Mainly opinions on applications Mainly generic opinions

Since 2003 >1000 scientific outputs

CONTAM Panel

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Mandate of the CONTAM Panel

To deliver scientific opinions on contaminants in food and feed, associated areas and undesirable substances i.e. natural toxicants, mycotoxins and residues of non authorised substances not covered by another Panel.

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Work areas - I

• Chemical compounds which are not intentionally added to food and feed such as metals and metal-organic compounds, mycotoxins and persistent organic pollutants and other compounds.

• Chemical compounds naturally found in food and feed such as phycotoxins, plant toxicants, or other compounds.

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Work areas - II

• Chemical compounds formed during thermal food and feed processing.

• Non-authorised substances in feed and food.

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Members of CONTAM Panel 2009 - 2012

• Chair: Dr. Josef Schlatter (CH)• Vice-chairs: Dr. Diane Benford (UK), Prof. Dr. Rolaf van Leeuwen (NL)• 20 Panel members • More information about the CONTAM experts

http://www.efsa.europa.eu/EFSA/ScientificPanels/CONTAM/efsa_locale- 1178620753812_PanelMembersContam.htm

CONT

AM

A-Z

MandatePanel Working Group (WG)

Opinion adopted

CONTAM Panel at work

CONTAM Unit

WG marine biotoxinsWG leadWG previous cargoesWG melamineWG ambrosiaWG brominated flame retardants DATEX

Unit

AMU Unit

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An opinion is based on the four pillars of risk assessment

HAZARD IDENTIFICATION

EXPOSURE ASSESSMENTLevels in food in EU, EU dietary

exposure (general population, high consumers, sub-groups) relevant food groups,

Proxy non-food sources, time trends

HAZARD CHARACTERISATIONADME, acute, subchronic & chronic toxicity human studies genotox, reprotox,immunotox,dose-response, mode/mechanism of action,selection of critical dataset, mathematical modelling (BMD), health based guidance

value

e.g. TDI

RISK CHARACTERISATIONRelating exposure to health-based guidance value

or Margin of Exposure (MOE) Vulnerable groups (children –

high level consumers)

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Requestor of opinions

Requests mainly related to generic scientific opinions Art. 29 Regulation (EC) 178/2002

Overview of CONTAM outputs

CONTAM: 70 scientific outputs since 2003

FOOD 30

Metals 3

Mycotoxins 3

Persistent organic pollutants 4

Marine biotoxins 8

Food processing 3

Other 9

FEED 40

Metals 4

Mycotoxins 5

Persistent organic pollutants 9

Plant toxicants 9

Coccidiostats 11

Others 2

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40

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RA for EU- Consumers from contaminants in FOOD

RA for animals from contaminants in FEED and impact on human health

Assessment of EU limits on human health and methods of analysis for marine biotoxins

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Topics Nitrate in Vegetables

PFOS/A

Polycyclic aromatic hydrocarbons (PAH)

3-MCPD esters (statement)

Undesirable substances in animal feed:- Natural plant products (ricin, gossypol; theobromine, tropane alkaloids)- Mercury

Coccidiostats: halofuginone, decoquinate, robenidine, nicarbazin, diclazuril (a total 11 from 2007 onwards)

Marine biotoxins in shellfish (yessotoxins; azaspiracids)

CONTAM Panel outputs 2008

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EFSA's rapid responses in 2008Art. 13 b of the “decision concerning the establishment and operations of the scientific committee and panels” adopted by the Management Board of EFSA on 11 September 2007 provides the basis for rapid responses.

• Mineral oil in sunflower oil• Melamine in food• Dioxin in Irish pork

Statements issued by EFSA and not by the CONTAM Panel.However, some experts of the scientific panels provided scientific advice to EFSA during the drafting of these statements.

RA for EU-Consumers from contaminants in FOOD

RA for animals from contaminants in FEED and impact on human health

Assessment of EU limits on human health and methods of analysis for marine biotoxins

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Topics Cadmium

Uranium in mineral water/foodstuffs

Previous cargoes (criteria + evaluation)

Arsenic

Aflatoxins in tree nuts other than almonds, hazelnuts, pistachios (statement)

Undesirable substances in animal feed:- Natural plant products (Saponins from Madhuca longifolia)- Nitrites

Marine biotoxins in shellfish (saxitoxins, pectenotoxins, domoic acid,Summary regulated marine biotoxins, Influence of processing on lipophilic marine biotoxins (statement),Palytoxins

CONTAM Panel outputs 2009 (status Oct)

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EFSA's rapid responses in 2009Art. 13 b of the “decision concerning the establishment and operations of the scientific committee and panels” adopted by the Management Board of EFSA on 11 September 2007 provides the basis for rapid responses.

• Nicotine in wild mushrooms

Statements issued by EFSA and not by the CONTAM Panel.However, CONTAM Panel chair provided scientific advice to EFSA during the drafting of this statement.

Some examples

okadaic acid 27 November 2007

azaspiracids 9 June 2008

yessotoxins 2 December 2008

saxitoxins 25 March 2009

pectenotoxins 27 May 2009 domoic acid 2 July 2009

summary opinion 13 August 2009

statement on the influence of processing 25 March 2009

CONTAM opinion – marine biotoxins

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Terms of reference

EFSA has been requested by the European Commission to assess: – the methods of analysis for various marine

biotoxins,– the current EU limits of marine biotoxins as

established in the EU legislation with regard to human health,

– new emerging toxins.

Established acute reference doses (ARfD’s)

Toxin Species Effect ARfD

Azaspiracids Human Gastrointestinal 0.2 µg AZA-1 eq/kg bwOkadaic acid- group Human Gastrointestinal 0.3 µg OA eq/kg bw

Saxitoxins Human Neurotoxicity 0.5 µg STX eq/kg bw

Pectenotoxins Mouse Gastrointestinal 0.8 µg PTX-2 eq/kg bw

Yessotoxins Mouse Cardiotoxicity 25 µg YTX eq/kg bw

Domoic acidHumans/Monkeys Neurotoxicty 30 µg DA/kg bw

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Comparison of current EU limits with ARfD’s

Toxin Current EU limits

Exposure by eating 400 g portion at the EU

limitARfD

Max. concentration

based on 400 g portion

OA 160 µg OA equivalents/kg SM

64 μg OA equivalents/person(1 μg OA eq/kg bw)

0.3 μg OA equivalents/

kg bw

45 μg OA equivalents/kg SM

AZA 160 µg AZA equivalents/kg SM

64 μg AZA1 equivalents/person

(1 μg AZA1 eq/kg bw)

0.2 μg AZA1 equivalents/

kg bw

30 μg AZA1 equivalents/kg SM

PTX 160 µg OA equivalents/kg SM

64 μg PTX2/person(1 µg PTX2 eq/kg bw)

0.8 μg PTX2 equivalents/

kg bw

120 µg PTX2 equivalents/kg SM

YTX 1 mg YTX equivalents/kg SM

400 µg YTX equivalents/person

(6.7 μg YTX eq/kg bw)

25 μg YTX equivalents/

kg bw

3.75 mg YTX equivalents/kg SM

STX 800 µg PSP/kg SM320 µg STX

equivalents/person(5.3 μg STX eq/kg bw)

0.5 μg STX equivalents/

kg bw

75 μg STX equivalents/kg SM

DA 20 mg DA/kg SM 8 mg DA/person(130 μg DA/kg bw) 30 μg DA/kg bw 4.5 mg DA/kg SM

SM = shellfish meat 24

Toxin Ability to perform at the current EU limit value

Specificity

OA Probability 40% at 160 µg/kg None

AZA Probability 95%a) 160 µg/kg None

PTX Not defined, Limited chance at 160 µg/kg None

YTX Not defined None

Performance of reference method (MBA) for lipophilic biotoxins

a) Steep dose response for AZA: Only 5% probability to detect 80 µg/kg

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Toxin Method LOD/LOQ Specificity

STX MBA LOD 370 µg STX eq/kg Limited

HPLC-FLD LOD not reportedLOQ 10-80 STX eq/kg Adequate

DA HPLC LOD 0.2-1 mg DA/kgLOQ 1-2.5 mg DA/kg

Adequate (DA & epi-DA)

ELISA(screening)

LOD 0.003 mg DA/kgLOQ 0.01 mg DA/kg

Adequate (DA)

Performance of reference method (MBA) for hydrophilic biotoxins

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Overall conclusions – marine biotoxins

• Based on the available data it appears that the current EU regulatory limit values for OA-, AZA-, STX- and DA-group toxins are not sufficiently protective for consumers.

• For YTX and PTX the current EU limit appears to be sufficiently protective for consumers.

• The MBA for liphophilic marine biotoxins (OA, AZA, PTX, YTX) has shortcomings (high variablity of results, detection capacity) and is not considered an appropriate tool for control purposes.

• MBA is able to quantify STX-group toxins at current EU limit, but not below.

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CONTAM opinion – cadmium

Cadmium 30 January 2009

Cd

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Terms of reference

EFSA has been requested by the European Commission to:

• Assess whether PTWI of 7 g/kg b.w. is still appropriate• Updated exposure assessment on cadmium

– Exposure from food including drinking water– Importance of other non-dietary sources (e.g. air,

cigarette smoke etc.)– Exposure in specific group of population (e.g. infants

and children, people following specific diets) and indication of age group most exposed to cadmium

• Take into account biomonitoring data

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Occurrence data (period 2003-2007)

• Total of 137,202 data from • 18 EU Member States

– Germany (32% of analysed data)– Slovakia (29% of analysed data)– France (13% of analysed data)– Romania (9% of analysed data)

• Iceland• Australia• Three commercial organisations

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Consumption data

• The EFSA Concise European Food Consumption database was established by EFSA to support exposure assessments in the EU - EFSA website (see Annex 3 to EFSA, 2008)

• French data for vegetarians - Appendix 1 of the 1st

French Total Diet Study (Leblanc et al., 2004)• Food survey from the Italian Istituto Nazionale di Ricerca

per gli Alimenti e la Nutrizione (INRAN) (Turrini et al., 2001; Turrini and Lombardi-Boccia, 2002) for children exposure

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Exposure to cadmium from different sources

Source Pathway

Range of calculated or reported exposures

[µg/kg b.w. per week]

Adults Children

Dietary exposureFood average current opinion Oral 1.89 - 2.96 2.56-3.46

Food high current opinion 2.54-3.91 5.49

Food in industrial areas Oral 3.3 - 5.8 4.6

Extreme diets current opinion Oral 2.87-4.64

Vegetarians Oral 5.47

Non-Dietary Exposure

House dust Oral 0.076 0.607

Air Inhalation 0.0024 0.0033

Smoking inhalation 0.35-0.70 -

Toxicity

• Cadmium is primarily toxic to the kidney, especially to the proximal tubular cells. Prolonged and/or high exposure may lead to – tubular damage – renal impairment with decreased glomulare filtration rate– renal failure

• Cadmium can also cause bone demineralisation either through direct bone damage or indirectly as a result of renal failure.

Cd

Human data

• A large number of studies on health effects of cadmium exposure in humans in different countries investigated the relationship between urinary cadmium levels and tubular effects.

• Tubular damage is the earliest effect of cadmium exposure, thus the CONTAM Panel based its risk assessment on this effect.

• The CONTAM Panel selected beta-2- microglobulin (B2M) in relation to tubular effects as the most useful biomarker.

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Meta-analysis

• The CONTAM Panel carried out a meta-analysis to evaluate the dose-response-relationship between the urinary cadmium and B2M.

• The CONTAM Panel derived a benchmark dose and its 95%- confidence lower bound (BMDL) for humans using cut off points relevant to clinical changes in the target organ (300 µg/g creatinine).

• The CONTAM Panel selected an overall group-based BMDL5 of 4 µg cadmium / g creatinine

• The CONTAM Panel applied a chemical-specific adjustment factor (CSAF) of 3.9 due uncertainties using group means and not individual data points.

• Dividing the BMDL5 of 4 µg cadmium/g creatinine by 3.9 (CSAF) results to urinary cadmium excretion of 1 µg/g creatinine 35

Meta-analysis

• The CONTAM Panel concluded that urinary cadmium concentrations of 1 µg per g creatinine and below would indicate that 95% of the European population would not exceed cut-off limits in the range of about 300 µg/g creatinine for B2M in urine.

• A one-compartment model was fitted to the data from population based Swedish mammography cohort study in order to derive a dietary cadmium intake from a urinary cadmium concentration.

• In order to remain below 1 µg cadmium/g creatinine the average daily dietary cadmium intake should not exceed 2.52 µg cadmium/kg b.w. per week

• Thus, the CONTAM Panel established a TWI of 2.5 µg/kg b.w. for cadmium.

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Risk characterisation

• Mean dietary exposure to cadmium across Europe was estimated to be 2.3 µg/kg b.w. per week (range: 1.9 to 3.0 range)

• High exposure was estimated to be 3.0 µg/kg. b.w. per week (range: 2.5 to 3.9)

• Vegetarians have dietary exposure estimates of 5.4 µg/kg. b.w. per week.

• The CONTAM Panel noted that the mean dietary exposures in European countries are close or exceeding the TWI of 2.5 µg/kg. b.w.

• Subgroups e.g. vegetarian, children, smokers and people living in highly contaminated areas may exceed the TWI by about 2-fold.

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Overall conclusions

• Although adverse health effects on kidney function are unlikely to occur for an individual exposed at this high level, the CONTAM Panel concluded that exposure to cadmium at the population level should be reduced.

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Follow up of risk assessments

Risk management follow up of CONTAM opinions

Aflatoxin B1: EU legislation. No need to change current maximum level (ML) in Com. Directive 2002/32/EC

Deoxynivalenol No EU legislation. Recommended guidance values e.g. for cereals, maize products and compound feed (Com. Recommendation 2006/576/EC)

Zearalenone No EU legislation. Recommended guidance values e.g. for cereals, maize products and compound feed (Com. Recommendation 2006/576/EC)

Ochratoxin A No EU legislation. Recommended guidance values e.g. for cereals, cereal products and compound feed (Com. Recommendation 2006/576/EC)

Ergot alkaloids EU legislation. Recommendation for increased monitoring and guidance values for combined ergot alkaloids in preparation

Fumonisins No EU legislation. Recommended guidance values e.g. for maize, maize products, and compound feed (Com. Recommendation 2006/576/EC)

EXAMPLE – Mycotoxins as undesirable substances in animal feed

11 Coccidiostats 3 % carry-over rate for non-sensitive non-target animal species compared to the authorised maximum concentration for feed for target animal species. 1% carry-over rate for sensitive non- target animal species and finishing feed compared to authorised maximum concentration for feed for target animal species.

Risk management follow up of CONTAM opinions

EXAMPLE – unavoidable carry-over of authorised coccidiostats into non-target feed

Work programme (ongoing and outlook)

RA for EU- Consumers from contaminants in FOOD

RA for animals from contaminants in FEED and impact on human health

Others

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Topics/deadlin e

Lead (WG on Lead) / Nov 2009*)

Brominated flame retardants (WG BFR) / June 2010*)

Ambrosia in animal feed (WG ambrosia)/March 2010

Marine biotoxins in shellfish: cyclic imines, palytoxins, brevetoxins, and ciguatoxin (WG marine biotox)/ Dec 2009*)

Previous cargoes (WG previous cargoes)/ Nov 2009

Melamine (WG on melamine) March 2010

CONTAM work programme 2009 in progress

*) extension of the deadline will be asked to European Commission

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FOOD

• Ergot alkaloids

• Morphine in poppy seeds

• Mycotoxins such as Alternaria toxins, T-2 and HT-2 toxin

• Aflatoxins (Aflatoxin total vs B1 for all food commodities with ML)

Possible requests in 2009/2010

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FEED• Mycotoxins such as Alternaria toxins, T-2 and HT-2

toxin, nivalenol.

• Use of glycerin from biodiesel production in animal feed

Possible requests in 2009/2010

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Regulation (EC) No 470/2009 of the European Parliament and of the Council of 6 May 2009laying down Community procedures for the establishment of residue limits of pharmacologically active substances in foodstuffs of animal origin, repealing Council Regulation (EEC) No 2377/90 and amending Directive 2001/82/EC of the European Parliament and of the Council and Regulation (EC) No 726/2004 of the European Parliament and of the Council

Art. 19 concerns EFSA (most likely CONTAM)

Possibly requests to EFSA to carry out risk assessments related to residues of veterinary medicinal products which are not authorised for use in EC.

Possible requests in 2009/2010

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Thank you very much for your attention !

EFSA: http://www.efsa.europa.eu