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EU Dietary Intake Estimates – Focus on Enzymes

Danika Martyn, PhD Scientific & Regulatory Consultant, Food & Nutrition Group, Intertek Scientific & Regulatory Consultancy, U.K.

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What is dietary exposure assessment?

“ ’Tis the dose that makes the poison ”

-Paracelsus

Anything when consumed in sufficient quantities can be toxic

Exposure = Amount food consumed * Amount component in food(mg/kg bw/day) (kgfood/kg bw/day) (mg/kgfood)

Enzymes

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Typical approach to estimating exposure

1. Screening methods • Makes broad assumptions on food and beverage consumption and proportion of

foods containing compound

2. National dietary survey summary statistics• Provide mean and upper percentile exposure estimations

• Presentation for food categories; entire population or fixed population groups; including body weight data

3. Individual food consumption data• Provide distribution of exposure estimates

• Presentation for individual foods; allows calculation for population group of interest; individual body weight data

• Probabilistic assessments - use of market share, brand loyalty etc.

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Typical approach to estimating exposure

Enzymes Additives Novel Foods FlavouringsBudget method with no factors• Simple

FAIM• Simple• Provides % breakdown by

food group

FAIM (?)• Simple• Provides % breakdown by

food group

Added Portion Exposure Techniques • Simple – standard

portion sizes provided

A: EFSA Comprehensive• User-friendly format

B: Budget method with specific factors• Data may be available

from literature

EFSA Comprehensive• User-friendly format• Provides intake values per

survey, per age group, on an absolute and body weight basis

EFSA Comprehensive• User-friendly format• Provides intake values per

survey, per age group, on an absolute and body weight basis

Individual Food Consumption Data (e.g., NDNS)• Distribution of intakes• Most realistic estimate• Not dependant on summary statistics and assumptions re heavy level intakes

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Typical approach to estimating exposure

Enzymes Additives Novel Foods FlavouringsBudget method with no factors• Unrealistic

FAIM• Broad categories results

in overestimation

FAIM (?)• Novel ingredient are rarely

intended for use in categories FCS

Added Portion Exposure Techniques • No further refinement

available

A: EFSA Comprehensive• Difficult for applicant to

obtain information required for use

• Requires assumptions to be made

• Resource intensive

B: Budget method with specific factors• Case-by-case – no

guidance

EFSA Comprehensive• Summary statistics• Requires assumptions to

be made• Resource intensive• Range must be

presented per age group

EFSA Comprehensive• Summary statistics• Requires assumptions to

be made• Resource intensive• Range must be presented

per age group

Individual Food Consumption Data (e.g., NDNS)• Resource intensive• Require input regarding use level of product in final foods – issue for enzymes (as per

Comprehensive)

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Enzymes

Food Enzyme: “means a product obtained from plants, animals or micro-organisms or products thereof including a product obtained by a fermentation process using micro-organisms:

i. containing one or more enzymes capable of catalyzing a specific biochemical reaction; and

ii. added to food for a technological purpose at any stage of the manufacturing, processing, preparation, treatment, packaging, transport or storage of foods;”

Regulation (EC) No. 1332/2008

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Basic considerations

• “Food enzymes” are in most cases not a pure isolated enzyme – exposure must be calculated on the basis of the “total organic solids”

• Food enzymes are generally added on the basis of their activity. Thus the lower the activity, the more TOS is added

• Enzyme exposures should be expressed as mg/kg bodyweight/day considering the lowest activity level (i.e. highest TOS)

• EFSA has identified a margin of exposure of 3001

1 Factor 10 for inter-species difference, factor 10 for intra-species difference and factor 3 for the extrapolation from short-term studies to chronic studies (EFSA Scientific Committee, 2012)

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EFSA Safety Evaluation of Food Additives

Critical issues of risk assessment:

• The source

• The food enzyme

• Intended and unintended reaction products

• The dietary exposure of the consumer

Depends on the residual concentration of the food enzyme(s) and other constituents of the food enzyme in the foods at the time of consumption and the amount and frequency of their consumption

1 http://www.efsa.europa.eu/en/efsajournal/pub/1305

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Dietary Exposure

“Potential human exposure to the food enzyme and to any other constituent or by-product of concern should be assessed considering all proposed uses. A conservative technique such as the “budget method” (Hansen, 1966; Hansen 1979; Douglass et al., 1997; European Commission 1998; FAO/WHO 2008) should be used to assess potential dietary exposure in a standard adult of 60 kg body weight consuming large amounts of the categories of foods and beverages for which use levels have been proposed, assuming that they always contain the food enzyme at its proposed upper use level. If needed, the technique should be adapted to consider the potential higher consumption per kg body weight of these foods and beverages in children. All assumptions and data used for the dietary exposure assessment should be clearly described and justified.

In case the use of the food enzyme is proposed for products specifically designed for infants (0-12 months) or young children (12-36 months) as defined in the Commission Directive 2006/141/EC, ad hoc conservative exposure estimates must be produced taking specifically into account these population groups.”

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Budget Method

Assumptions:

• Food and non-milk beverage intake (0.05 kg and 0.1 L per kg bw/day)

• Percentage of foods and beverages that are processed (~50%)

• Percentage of processed foods and beverages containing the food additive (~25-50%)

Consumption of Foods and Beverages (kg/kg bw/day)

Consumption of Foods and Beverages for 70-kg adult1

(kg/day)

Percentageof Processed Products (%)

Percentage of Processed Products Containing Additive (%)

Consumption of Foods and Beverages Containing Additive (kg/day)

Solid foods 0.05 3.5 50 50 0.875

Non-Milk Beverages

0.10 7.0 50 50 1.75

Total 2.625

1 http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/2579.pdf

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Issues with approach

1. Budget method assumptions (or standard factors) not validated for enzymes

• Additives have a technological function in the final food

2. Missing data on residual levels in foodstuffs as consumed

• Use levels often presented for substrate – requires information on conversion factors (‘substrate’ to ‘product’)

• No information on use level of ‘product’ in final foods and beverages

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EFSA Draft Statement

Draft Statement published1

Info session held2

‘Traditional’ budget method not suitable for enzymes and there needs to be guidance on refinements steps

New tiered approach proposed:

• Tier 1: Budget method without standard factors

• Tier 2A: EFSA Comprehensive Database

• Tier 2B: Budget method with specific factors

1 http://www.efsa.europa.eu/sites/default/files/consultation/160216.pdf2 http://www.efsa.europa.eu/en/events/event/160203#documents

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EFSA Proposed Tier 1

Budget method without standard factors

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Tier 1: Budget method without standard factors

Consumption of Foods and Beverages Processed with Enzyme (kg/kgbw/day)

Consumption of Foods and Beverages for 70-kg adultProcessed with Enzyme (kg/day)

Percentageof Processed Products (%)

Percentage of Processed Products Containing Additive (%)

Consumption of Foods and Beverages Containing Additive (kg/day)

Solid foods 0.05 3.5 50 50 0.875

Non-Milk Beverages

0.10 7.0 50 50 1.75

Total 10.5 2.625

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Considerations

Removal of standard factors:

• Results in intake levels that are highly unrealistic –10.5 kg of foods and beverages per day processed with enzyme

• Food enzymes are processing aids – therefore some factor to account for proportion of foods/beverages that are processed

• No factor for ingredients

Dossiers submitted may have an exposure level which is 4- to 6- times higher than the level estimated using the suggested approach

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EFSA Proposed Tier 2A

EFSA Comprehensive Database (Nutrition Surveys)

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Tier 2A: EFSA Comprehensive Database

• Database of summary statistics based on survey data from EU Member States

• Apply concentration of food enzyme to FoodEx categories

• Calculate upper percentile for total population

• Tiered approach recommended

FoodEx Level 1 Milk and dairy products

FoodEx Level 4 Acidophilus milk

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Considerations

Comprehensive Database1 is user-friendly…

1 http://www.efsa.europa.eu/en/food-consumption/comprehensive-database

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Considerations

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Considerations

Comprehensive Database1 is user-friendly, howeverpoints such as:

1. Calculation of upper percentiles

• Need to consider trends of intake (food groups which may be consumed together)

• EFSA Guidance document2

2. Selection of suitable food groups

need to be considered carefully, particularly at lower (more refined) FoodEx levels

1 http://www.efsa.europa.eu/en/food-consumption/comprehensive-database2 http://www.efsa.europa.eu/en/efsajournal/pub/2097

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Considerations

• Difficulty in obtaining all required data to conduct assessment

• However, allows “educated overestimates” the levels of consumption are likely to be far more realistic than Proposed Tier 1

Activity of enzyme

TOS of enzyme

Conversion rate to ingredient

Maximum level of ingredient in final food

Enzyme Producer× ×

Ingredient Producer × × ×Final food Producer × × ×

Applicant

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EFSA Proposed Tier 2B

Adjusted Budget Method with Specific Factors

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Tier 2B: Budget method with specific factors

Proposed for use when it is not possible to obtain information necessary to conduct the EFSA Comprehensive

Activity of enzyme

TOS of enzyme

Conversion rate to ingredient

Maximum level of ingredient in final food

Enzyme Producer× ×

Ingredient Producer × × ×Food Producer

× × ×

Applicant

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Tier 2B: Budget method with specific factors

‘Adjusted’ budget method

Case-by-case basis• Comprehensive Database

• Literature

• Food industry

Consumption of Foods and Beverages (kg/kg bw/day)

Consumption of Foods and Beverages for 70-kg adult (kg/day)

Percentageof Processed Products (%)

Percentage of Processed Products Containing Enzyme (%)

Consumption of Foods and Beverages Containing Enzyme (kg/day)

Solid foods 0.05 3.5 ? ? ?

Non-Milk Beverages

0.10 7.0 ? ? ?

Total ?

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Considerations

• Alternative when information is not available

• Not based on actual consumption data

• Burdensome

• Case-by-case – difficult for applicants to ensure robustness of approach

• Submit without assurance whether approach is acceptable?

• Will EFSA perform own assessment and result in an MOE below 300?

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Next Steps?

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Next Steps for Process

• Finalise statement after public consultation (deadline: 31/03/2016)

• Requests for data

• Preparation of a FAIM-like tool?• Mutually-exclusive food categories? Case-by-case

Activity of enzyme

TOS of enzyme

Conversion rate to ingredient

Maximum level of ingredient in final food

Enzyme Producer× ×

Ingredient Producer × × ×Food Producer

× × ×

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Conclusions

In order to conduct exposure assessments, information on final concentration of TOS in foods as consumed is needed and it is notalways easy to get. Thus there will always need to be assumptions made

EFSA’s current guidance for enzymes intakes is based on the ‘traditional’ Budget Method that assumes ~2.6 kg of foods and beverages per day contain enzyme

Proposed Tier 1 ~quadruples that

Proposed Tier 2A will probably provide a much more accurate overestimation but requires a lot of information

Proposed Tier 2B is suitable if there is no way to get information on the final applications, but still requires considerable input, and has a lot of uncertainties

A 300-fold safety factor is required when compared against the safety level

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Thank you!

danika.martyn@intertek.comwww.intertek.com/food/consultingDanika Martyn, PhD

Scientific & Regulatory Consultant, Food & Nutrition Group, Intertek Scientific & Regulatory Consultancy, U.K.

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