Assessment of Exposure to Food Chemicals Catherine Leclercq INRAN National Research Institute on Food and Nutrition Catherine Leclercq INRAN National Research

Assessment of Exposure to Food Chemicals

Assessment of Exposure to Food Chemicals

Catherine LeclercqINRAN

National Research Institute on Food and Nutrition

Catherine LeclercqINRAN

National Research Institute on Food and Nutrition

September 28th, 2003 INRAN – Rome, Italy Catherine Leclercq

Methodological Aspects for the Collection and use of Data on Food

Intake and Chemical Concentration

Methodological Aspects for the Collection and use of Data on Food

Intake and Chemical Concentration

RISK ANALYSISRISK ANALYSIS


- Risk assessmentexposure assessment

- Risk management

- Risk communication

- Risk assessmentexposure assessment

- Risk management

- Risk communication

Exposure Assessment is becoming

increasingly important

Exposure Assessment is becoming

increasingly important

Consumers demand information on exposure

Exposure assessment is needed to prioritise risk assessment

Consumers demand information on exposure

Exposure assessment is needed to prioritise risk assessment


AllarmsAllarms

Consumer


Food ContactFood Contact Material Material

Heavy metalsHeavy metalsToxic substancesToxic substances

PreservatiPreservativesves

leadlead

cadmiumcadmium

mercurymercury

dioxinedioxine

acrilamideacrilamidemycotoxins

mycotoxins

Delta-decatactone

Delta-decatactone

Allyl caproate

Allyl caproate

EucalyptolEucalyptol

Isoaly

l aceta

teIs

oaly

l aceta

te

Furfuryl alcohol

Furfuryl alcohol

FlavouringsFlavourings

Natural Natural toxicantstoxicants

cyanogenic glycosides

cyanogenic glycosides

solaninesolanine

lectinslectins

canthaxanthcanthaxanthin in

tartrazin

e

tartrazin

e

xanthophyllxanthophylls s

ColourColours s

nitritenitrite

nitrate

nitratesodium sodium

sulfite sulfite

SweeteniSweetening agentsng agents

sucralos

sucralose e

aspartam

aspartam

ee

alitamealitame

acesulfame

acesulfame

KK

saccharisaccharinn antimony

antimony trioxidetrioxide

polyethylepolyethylenene

silver zeolite Asilver zeolite A


Exposure assessment should allow to answer the question:

The level of intake of a specific substance is such as to constitute a

health risk for consumer?

Chemical hazards may thus be ranked not only according to their toxicity but according to the level

of risk deriving from their presence in the diet

Exposure assessment should allow to answer the question:

The level of intake of a specific substance is such as to constitute a

health risk for consumer?

Chemical hazards may thus be ranked not only according to their toxicity but according to the level

of risk deriving from their presence in the diet


Exposure analysis is aimed at assessing chronic and acute exposure to various substances present in the diet that may constitute a health hazard for the consumers and at comparing it with their respective safety limits.


EXPOSURE EXPOSURE ASSESSMENASSESSMEN

TT

EXPOSURE EXPOSURE ASSESSMENASSESSMEN

TT

FOOD CHEMICAL DATAFOOD CHEMICAL DATA

Maximum Permitted Maximum Permitted LevelLevel

Highest Reported Highest Reported LevelLevel

Trial mean or medianTrial mean or median

Monitoring dataMonitoring data

Correction factors Correction factors appliedapplied

As consumedAs consumed

TARGET TARGET GROUP BODY GROUP BODY WEIGHTWEIGHT

FoetusFoetus

InfantInfant

ChildrenChildren

AdultsAdults

RISK RISK CHARACTERIZATIOCHARACTERIZATIONN

Acute RfDAcute RfD

ADIADI

TDITDI

FOOD CONSUMPTION FOOD CONSUMPTION (including drinking (including drinking water)water)

Highest reportedHighest reported

High percentileHigh percentile

MedianMedian

Mean (eaters only)Mean (eaters only)

Mean populationMean population

OTHER FACTORSOTHER FACTORS

Nutritional status Nutritional status (malnutrition)(malnutrition)

OccupationOccupation

Health statusHealth status

AgeAge

GenderGender

GeneticsGenetics

MultimediaMultimedia

EXPOSURE EXPOSURE TIMETIME

Life timeLife time

YearYear

MonthMonth

WeekWeek

DayDay

One mealOne meal


Safety limits for ACUTE TOXICITYACUTE TOXICITY: Tolerable Levels of Intake per kg body weight

TDI (Tolerable Daily Intake)TDI (Tolerable Daily Intake)TWI (Tolerable Weekly Intake)TWI (Tolerable Weekly Intake)TMI (Tolerable Monthly Intake)TMI (Tolerable Monthly Intake)

These safety limits are used for contaminants and withdrawn pesticides persisting in the environment as contaminants (DDT)

Safety limits for ACUTE TOXICITYACUTE TOXICITY: Tolerable Levels of Intake per kg body weight

TDI (Tolerable Daily Intake)TDI (Tolerable Daily Intake)TWI (Tolerable Weekly Intake)TWI (Tolerable Weekly Intake)TMI (Tolerable Monthly Intake)TMI (Tolerable Monthly Intake)

These safety limits are used for contaminants and withdrawn pesticides persisting in the environment as contaminants (DDT)


ACUTE EXPOSUREACUTE EXPOSURE

Within an eating occasion or a day

Intake must be assessed as total intake within a restricted time interval (meal or day)

Within an eating occasion or a day

Intake must be assessed as total intake within a restricted time interval (meal or day)


Safety limits for CHRONIC TOXICITYCHRONIC TOXICITY: Acceptable Daily Intake (ADI)

Safety limits for CHRONIC TOXICITYCHRONIC TOXICITY: Acceptable Daily Intake (ADI)

““The amount of a food additive, The amount of a food additive, expressed on a mg/kg body weight expressed on a mg/kg body weight

basis,basis, that can bethat can be ingested daily over ingested daily over a lifetimea lifetime without incurring any without incurring any

appreciable health risk, and is based appreciable health risk, and is based on an evaluation of available on an evaluation of available

toxicological data”toxicological data”

Scientific Commitee for Food, 1991.Scientific Commitee for Food, 1991.

““The amount of a food additive, The amount of a food additive, expressed on a mg/kg body weight expressed on a mg/kg body weight

basis,basis, that can bethat can be ingested daily over ingested daily over a lifetimea lifetime without incurring any without incurring any

appreciable health risk, and is based appreciable health risk, and is based on an evaluation of available on an evaluation of available

toxicological data”toxicological data”

Scientific Commitee for Food, 1991.Scientific Commitee for Food, 1991.


This safety limit is used for additives and authorised pesticides.This safety limit is used for additives and authorised pesticides.

CHRONIC EXPOSURECHRONIC EXPOSURE

Within lifetimeWithin lifetime

Intake must be assessed as mean Intake must be assessed as mean intake within a long period of timeintake within a long period of time

Within lifetimeWithin lifetime

Intake must be assessed as mean Intake must be assessed as mean intake within a long period of timeintake within a long period of time


Sum (Food chemical concentration x Food consumption)

body weight


Dietary exposure = Dietary exposure =

The main sources of information about the presence and level of occurrence of the different chemicals in foods and beverages are:

analytical determination (in single foods or in market basket studies or duplicate diet studies)

legislation (presence and Maximum Permitted Levels)

labels of packaged products (recipes and ingredients)

concentration data provided by the producers.

The main sources of information about the presence and level of occurrence of the different chemicals in foods and beverages are:

analytical determination (in single foods or in market basket studies or duplicate diet studies)

legislation (presence and Maximum Permitted Levels)

labels of packaged products (recipes and ingredients)

concentration data provided by the producers. September 28th, 2003 INRAN – Rome, Italy Catherine Leclercq

Food consumption data are continuously retrieved at different level of detail

Food Balance Sheets (GEMS Food Regional Diets)

Household Budget Surveys

food consumption surveys aimed at assessing nutrient intake

consumer surveys at brand level

Food consumption data are continuously retrieved at different level of detail

Food Balance Sheets (GEMS Food Regional Diets)

Household Budget Surveys

food consumption surveys aimed at assessing nutrient intake

consumer surveys at brand level


The study of additive exposure from diet must take into special consideration non-average individuals, and in particular those who consume relatively large quantities of foods containing higher concentrations of a food additive.But, the issue of what proportion of the population would have to exceed the ADI before action is considered necessary to reduce intakes is both a scientific and a political/ethical question. From a scientific point in many cases there are statistical difficulties in measuring adequate percentiles of intake.

The study of additive exposure from diet must take into special consideration non-average individuals, and in particular those who consume relatively large quantities of foods containing higher concentrations of a food additive.But, the issue of what proportion of the population would have to exceed the ADI before action is considered necessary to reduce intakes is both a scientific and a political/ethical question. From a scientific point in many cases there are statistical difficulties in measuring adequate percentiles of intake.


The objective is always to determine the proportion of the population that regularly exceeds the ADI. The highest percentiles of mean daily intake are therefore usually estimated.

The objective is always to determine the proportion of the population that regularly exceeds the ADI. The highest percentiles of mean daily intake are therefore usually estimated.

Example of a food chemical intake distributionExample of a food chemical intake distribution


Moreover the monitoring of additives intake have to be repeated regularly because the market of food products changes very rapidly in relation to both product formulation and consumer preferences.

The monitoring activity must be carried out by collecting and analysing data concerning food consumptions and additives presence and concentration in the same food products.

Moreover the monitoring of additives intake have to be repeated regularly because the market of food products changes very rapidly in relation to both product formulation and consumer preferences.

The monitoring activity must be carried out by collecting and analysing data concerning food consumptions and additives presence and concentration in the same food products.


The number of chemical substances that should be monitored is huge.

For example:

The food additives authorized in the EU are more than 300.

More than 2800 different flavouring substances are claimed by industry to be added to foods and beverages in Europe.

The number of chemical substances that should be monitored is huge.

For example:

The food additives authorized in the EU are more than 300.

More than 2800 different flavouring substances are claimed by industry to be added to foods and beverages in Europe.


Stepwise procedure: target detailed dietary exposure estimates to chemicals which might be of health concern for the general population or for certain at-risk groups.

Exposure is first assessed by using methods based on conservative assumptions.

If the estimated exposure to a given chemical substance exceeds its safety limit (ADI, TDI, etc.) a more accurate method of dietary exposure assessment should be applied.

Stepwise procedure: target detailed dietary exposure estimates to chemicals which might be of health concern for the general population or for certain at-risk groups.

Exposure is first assessed by using methods based on conservative assumptions.

If the estimated exposure to a given chemical substance exceeds its safety limit (ADI, TDI, etc.) a more accurate method of dietary exposure assessment should be applied. September 28th, 2003 INRAN – Rome, Italy Catherine Leclercq

As the accuracy of dietary exposure assessments increases, the cost of collecting adequate data and the resources needed to undertake the assessments also increase.

As the accuracy of dietary exposure assessments increases, the cost of collecting adequate data and the resources needed to undertake the assessments also increase.


An example of the stepwise approach in

the case of

ANTIOXIDANTS

(food additives)

An example of the stepwise approach in

the case of

ANTIOXIDANTS

(food additives)


AntioxidantsFood products in which the use is permitted

MPL

Butylated Hydroxyanisole (BHA) (E320)and Gallates(E310-E312)

Chewing gum, dietary supplements 400

mg/kgAnimal fats and oils; Fats and oils for the professional manufacture of heat-treated foodstuffs Cake mixes, cereal-based snack foods, milk powder for vending machines, dehydrated soups and broths, sauces, dehydrated meat, processed nuts,seasonings and condiments, pre-cooked cereals

200 mg/kg

Dehydrated granulated potatoes 25

mg/kg

Erythorbic acid and its salts(E315-E316)

Semi-preserved and preserved meat products

500 mg/kgSemi-preserved and preserved fish

productsFrozen and deep-frozen fish with red skin

1500 mg/kg

Butylated Hydroxytoluene(BHT) (E321)

Animal fats and oils Fats and oils for the professional manufacture of heat-treated foodstuffs

100mg/kg

Chewing gum, dietary supplements 400

mg/kg


Step 1 - Budget Method: It is based on the existence of a physiological upper limit to the amount of food and drink that can be ingested each day: maximum energy intake: 50 kcal / kg bw / day maximum liquid intake: 100 ml/kg bw / dayIn a 60 kg subject: 1.5 kg of food and 6 l of beverages per day.

Further assumptions: The additive is always used at its highest MPL in foods and in beverages (considering only significant uses) The proportion of the diet that may contain the additive can be roughly estimated.

Method used by CODEX FAC and within SCCOP projects (European Commission).

Step 1 - Budget Method: It is based on the existence of a physiological upper limit to the amount of food and drink that can be ingested each day: maximum energy intake: 50 kcal / kg bw / day maximum liquid intake: 100 ml/kg bw / dayIn a 60 kg subject: 1.5 kg of food and 6 l of beverages per day.

Further assumptions: The additive is always used at its highest MPL in foods and in beverages (considering only significant uses) The proportion of the diet that may contain the additive can be roughly estimated.

Method used by CODEX FAC and within SCCOP projects (European Commission).


DANISH BUDGET METHOD:DANISH BUDGET METHOD: assessment of total assessment of total maximum daily intake based on maximum maximum daily intake based on maximum

physiological intakesphysiological intakesThe case of BHTThe case of BHT

TMDI = TMDI = (1.5 x 0.125 x 100 + 6 x 0) / 60(1.5 x 0.125 x 100 + 6 x 0) / 60 = =

0.312 =0.312 = 6.3 x ADI 6.3 x ADI

1/81/80%0%

(6 l)(6 l)(1.5 kg)(1.5 kg)

100 100 mg/kgmg/kg

Solid foodsSolid foods Liquid foodsLiquid foods


ADADI = 0.05 mg/kgI = 0.05 mg/kgADADI = 0.05 mg/kgI = 0.05 mg/kg

Step 2: method for which only aggregated data are required (i.e. Household Budget Survey data).

Step 2: method for which only aggregated data are required (i.e. Household Budget Survey data).


For each food category: Average Theoretical Intake (ATI) = Average consumption X MPL

For each food category: Average Theoretical Intake (ATI) = Average consumption X MPL

Extreme Theoretical Intake (ETI) = High consumption (95th percentile) X MPL Extreme Theoretical Intake (ETI) = High consumption (95th percentile) X MPL

Overall Theoretical Extreme Intake: sum of the two highest ETI + sum of the ATI of all the other categories.(intake in a high consumer of two food categories who is an average consumer of all the others)

Method developed within SCOOP Task 4.2 (European Commission)

Overall Theoretical Extreme Intake: sum of the two highest ETI + sum of the ATI of all the other categories.(intake in a high consumer of two food categories who is an average consumer of all the others)

Method developed within SCOOP Task 4.2 (European Commission)

Step 3: method for which consumption data at individual level are required (i.e. ad hoc food consumption surveys ).

Subjects recorded all foods and beverages ingested during 14 consecutive days. The weight of each single food recorded was transformed into the weight of single raw foods as described into the Italian national food composition tables.

The additive was always used at its MPL authorized in the corresponding food or beverage.

Step 3: method for which consumption data at individual level are required (i.e. ad hoc food consumption surveys ).

Subjects recorded all foods and beverages ingested during 14 consecutive days. The weight of each single food recorded was transformed into the weight of single raw foods as described into the Italian national food composition tables.

The additive was always used at its MPL authorized in the corresponding food or beverage.


Potential dietary intake of antioxidants.

Potential dietary intake of antioxidants.


Exposure models referred to other categories of chemicals:Exposure models referred to other categories of chemicals:


Veterinary drugs residues

MRL are such that 300 g X MRL in meat + 100 g X MRL in liver + 50 g X MRL in kidney + 50 g X MRL in animal fats + 100 g X MRL in eggs + 1,5 litres X MRL in milk < ADI

(99th percentile of eaters)

Veterinary drugs residues

MRL are such that 300 g X MRL in meat + 100 g X MRL in liver + 50 g X MRL in kidney + 50 g X MRL in animal fats + 100 g X MRL in eggs + 1,5 litres X MRL in milk < ADI

(99th percentile of eaters)

Migrants from Food Contact Materials

migration is such that intake of 1 kg of food in contact with 600 cm2 of the relevant food contact material < TDI

Migrants from Food Contact Materials

migration is such that intake of 1 kg of food in contact with 600 cm2 of the relevant food contact material < TDI

The International Estimate of Short Term Intake (IESTI): conservative method for the assessment of short-term dietary exposure to pesticide residues.

For each commodity separately: Weight a large portion (97.5th percentile of eaters on a single day) X highest residue level of contamination.(based on available data for food consumption and residue levels)

This method may not be used to assess overall theoretical intake: it can not be assumed that on a given day a consumer may consume large portions of all commodities all of them maximally contaminated.Proposed by FAO/WHO (2001)

The International Estimate of Short Term Intake (IESTI): conservative method for the assessment of short-term dietary exposure to pesticide residues.

For each commodity separately: Weight a large portion (97.5th percentile of eaters on a single day) X highest residue level of contamination.(based on available data for food consumption and residue levels)

This method may not be used to assess overall theoretical intake: it can not be assumed that on a given day a consumer may consume large portions of all commodities all of them maximally contaminated.Proposed by FAO/WHO (2001)


The Theoretical Added Maximum Daily Intake (TAMDI) is a conservative method used to assess exposure to flavouring substances.

Assumptions:- daily intake of 160.4 g/day of flavourable foods and 324 ml/day of flavourable drinks* - flavouring substance always present in foods and drinks at the “upper use level” specified by the Council of Europe.

* twice the quantity taken as likely to contain intense sweeteners according to CODEX.September 28th, 2003 INRAN – Rome, Italy Catherine Leclercq

assume 100% presence if legally permissible

assume presence always at legal maximum permitted level (MPL and MRL)

Conservative deterministic approach

Conservative deterministic approach

For all eating occasions of target foods:


Within the Montecarlo project,

refined databases have been

created for the purpose of

estimating as accurately as

possible ‘true’ chemical intakes in

order to assess the validity of

probabilistic models.

Within the Montecarlo project,

refined databases have been

created for the purpose of

estimating as accurately as

possible ‘true’ chemical intakes in

order to assess the validity of

probabilistic models.


Project coordinator: Institute of European Food Studies (Ireland)

Participants: School of Mathematics, TCD (Ireland)

TNO (The Netherlands) Institute of Human Nutrition, IOHN (UK)

RIKILT (The Netherlands)INRAN (Italy)

Gobierno Vasco (Spain).

Website: http://www.tchpc.tcd.ie/projects/montecarlo/

The Montecarlo projectThe Montecarlo project


Develop a comprehensive set of mathematical algorithms for stochastic modelling of a variety of food chemicals, nutrients and ingredients.

Develop customised software which can be accessed via the internet and linked to high performance computers.

Develop a comprehensive set of mathematical algorithms for stochastic modelling of a variety of food chemicals, nutrients and ingredients.

Develop customised software which can be accessed via the internet and linked to high performance computers.

Main objectivesMain objectives


I) Analysis of all the necessary components for stochastic modelling: identification of correlations and dependencies

II) Explore how variability in the input data on food intake and chemical concentration presentation may influence the output of stochastic models

III)Acquisition of data for validation studies

IV) Deliverables

V) Potential end users

I) Analysis of all the necessary components for stochastic modelling: identification of correlations and dependencies

II) Explore how variability in the input data on food intake and chemical concentration presentation may influence the output of stochastic models

III)Acquisition of data for validation studies

IV) Deliverables

V) Potential end usersSeptember 28th, 2003 INRAN – Rome, Italy Catherine Leclercq

Databases of “true” intakes of

food additives, based on brand level food consumption and ingredient composition.

pesticide residues, based on duplicate diets.

nutrients, based on biomarker studies.

Databases of “true” intakes of

food additives, based on brand level food consumption and ingredient composition.

pesticide residues, based on duplicate diets.

nutrients, based on biomarker studies.

Acquisition of data for validation studies

Acquisition of data for validation studies


Partners: RIKILT (The Netherlands) and Gobierno Vasco (Spain)Substances: Five pesticides (chlorpyrifos, iprodione, pirimicarb, pirimiphos-methyl, chlorfenvinphos)

Databanks available for stochastic modelling: Standard food consumption surveys, recipes database Pesticide residue database for Raw Agricultural Commodities Conversion factors of edible portions of food items into RAC

Additional information needed: pesticide content of individual diets processing factors for all pesticide-commodity combinations variability factors for all pesticide-commodity combinations

Method used for data collection: collection of duplicate diet and food diaries in 250 infants literature data on processing factors and variability factors

Hypothesis tested: a valid distribution of pesticides intake can be obtained from standard consumption surveys and pesticide residue databases if processing and variability factors are known.


Partner: INRAN (Italy)Substances: 2 intense sweeteners (saccharin, cyclamate)

Databanks available for stochastic modelling: Standard food consumption survey codified at food category level Household purchases at brand level

Additional information needed: individual food consumption at brand level additive presence and concentration at brand level additive intakes in high consumers

Method used for data collection: repeated registration of consumption of sugar-free products at brand level in both random and pre-screened high consumers (teenagers) creation of an ingredient database of sugar-free products with presence and concentration of intense sweetenersHypothesis tested: a valid distribution of additives intake can be obtained from

standard consumption survey, ingredient database and information on brand loyalty and market share; the model provides a valid estimate of intakes in high consumers.


Data typically needed to estimate food additive intake

Data typically needed to estimate food additive intake

• Mean population intake 30 g/d• Percentage of consumers 50%• Mean consumers intake 60 g/d• 97.5th %ile consumers intake 180

g/d

Key needs: Individual data with sufficient number

of subjects Accuracy of percentage consumers

(sufficient survey duration) control of under-reporting

• Mean population intake 30 g/d• Percentage of consumers 50%• Mean consumers intake 60 g/d• 97.5th %ile consumers intake 180

g/d

Key needs: Individual data with sufficient number

of subjects Accuracy of percentage consumers

(sufficient survey duration) control of under-reporting


FAO/WHO expert Committees on food chemical

JECFA: Joint FAO/WHO Expert Committee on Food Additives

http://www.who.int/pcs/jecfa/jecfa.htm

Evaluation of additives, flavourings, contaminants, naturally occuring toxicants, veterinary drugs (vet-

JECFA)

JMPR: Joint FAO/WHO Meeting on Pesticide Residueshttp://www.who.int/pcs/jmpr/jmpr.htm

Evaluation of pesticides


IPCSIPCSProject to update principles and methods for the risk assessment of chemicals in food

Project to update principles and methods for the risk assessment of chemicals in food

http://www.who.int/pcs/food_principles/principles.htmhttp://www.who.int/pcs/food_principles/principles.htm


Panel on Panel on plant health, plant health, plant plant protection protection products products and their and their residuesresidues

Panel on Panel on food food additives, additives, flavourings, flavourings, processing processing aids and aids and materials in materials in contact with contact with foodfood

Panel on Panel on geneticallgenetically y modified modified organismorganismss

Panel on Panel on additives additives and and products or products or substances substances used in used in animal feedanimal feed

Panel on Panel on dietetic dietetic products, products, nutrition nutrition and and allergiesallergies

Panel on Panel on biological biological hazards hazards (including (including TSE/BSE TSE/BSE issues)issues)

Panel on Panel on contaminacontaminants in the nts in the food chainfood chain

Panel on Panel on animal animal health health and and welfarewelfare


European Food Safety AuthorityEuropean Food Safety AuthoritySCIENTIFIC COMMITTEESCIENTIFIC COMMITTEE

INRAN National Research Institute on

Food and Nutrition

Research Group “Food Safety - Exposure Analysis”

www.inran.it/Ricerca/rischioalimentare

[email protected]


Documents

Assessment of Exposure to Food Chemicals Catherine Leclercq INRAN National Research Institute on Food and Nutrition Catherine Leclercq INRAN National Research