Micronutrient Risk Assessment Safety of Fortified Foods and Supplements

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1 Micronutrient Risk Assessment Safety of Fortified Foods and Supplements John N. Hathcock, Ph.D. Senior Vice President Scientific and International Affairs Council for Responsible Nutrition International Manno, Switzerland and Washington, DC CRN-International ILSI Mexico, 8 June 2011

2 Risk Assessment Scientific process to evaluate probability and consequences of adverse effects resulting from consumption of (or exposure to) a specific amount of any substance CRN-International ILSI Mexico, 8 June

3 Rationale for Risk Assessment for Safety of Fortified Foods and Supplements Maximums must be based on safety, not nutritional need required by Codex, European Commission, ASEAN, and many countries Safety is evaluated by risk assessment Maximums sometimes needed to assure consumer safety CRN-International ILSI Mexico, 8 June

4 Risk Assessment for Nutrients UL method is widely accepted because Developed by IOM, then accepted and refined by EFSA, EVM, Codex, etc. Uncertainty factors are adjusted on the o o o basis of strength of data severity of hazard uses fractional values if appropriate CRN-International ILSI Mexico, 8 June

5 UL Risk Assessment for Nutrients in Foods Identify any known hazard If found, apply UL method If not found, apply HOI method If data are insufficient for UL or HOI, look for History of Safe Use If none of above, new toxicological studies are needed CRN-International ILSI Mexico, 8 June

6 What is the UL? Definition: Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the general population CRN-International ILSI Mexico, 8 June

7 Who has adopted the UL method? WHO NAS-IOM CRN-International ILSI Mexico, 8 June

8 UL Procedure 1. Hazard identification (the type of adverse effect*) 2. Dose-response analysis 3. Uncertainty evaluation 4. Identification of UL *Codex defines hazard as an agent, not the effect; scientific groups define hazard as the adverse effect CRN-International ILSI Mexico, 8 June

9 Reasons for Using FAO/WHO Risk Assessment Method Developed by authoritative international organizations (FAO/WHO) Based on UL method developed and sanctioned by major national or regional scientific advisory groups (IOM, EFSA/SCF, EVM) Adopted by Codex, ASEAN Solves the major problem of original UL method: Describes Highest Observed Intake (HOI) approach for use when no UL can be set HOI approach adopted by industry and in peer-reviewed literature to avoid misunderstanding of absence of UL CRN-International ILSI Mexico, 8 June

10 What is the HOI? Definition: Highest Observed Intake (HOI)-- is derived only when no adverse health effects have been identified. It is the highest level of intake observed or administered as reported within (a) study(ies) of acceptable quality. CRN-International ILSI Mexico, 8 June

11 When UL is Not Possible Note: No UL is set without identified of a hazard and dose-response data this has been a major limitation of the UL for regulatory and policy applications UK EVM report avoided this problem CRN & IADSA 2004 reports used the Observed Safe Intake (OSL) method = HOI the January 2006 FAO-WHO report on risk assessment defined a Highest Observed Intake (HOI) when no UL value is identified CRN-International ILSI Mexico, 8 June

12 HOI Risk Assessment 1. Assess data to identify any hazard (if found, use UL method) 2. Dose-response analysis to identify highest intake with sufficient data to exclude adverse effects (HOI) 3. Evaluate uncertainty 4. Select reasonable HOI CRN-International ILSI Mexico, 8 June

13 FLOW CHART: Evaluate data for evidence of toxicity or no toxicity Toxicity No toxicity Dose-response assessment to identify NOAEL or LOAEL Select an uncertainty factor (UF) for data quality Calculate UL = NOAEL (or LOAEL) UF If no evidence of toxicity, a NOAEL or LOAE cannot be set and no UL can be calculated Apply Highest Observed Intake Method (HOI) = the highest level with adequate evidence of no toxic effects use HOI instead of UL CRN-International ILSI Mexico, 8 June

14 Established toxicity: Classic UL method applied UL NOAEL HOI No established toxicity: HOI method applied No data range CRN-International ILSI Mexico, 8 June

15 Importance of the HOI Method: Vitamin B12 Example No established toxicity (i.e. no known hazard) US FNB, EC SCF = no UL established Absence of UL may be perceived as absence of safety data BfR (Germany) = 9 mg (3xRDA) (proposed not set) MEFI (France) = 3 mg (1xRDA) (regulatory maximum) UK EVM = 2000 mg Guidance Level CRN ULS (OSL) = 3000 mg Some ordinary foods contain up to 50 to 100 mg Aging decreases vitamin B12 absorption and increases dietary needs to 25 t0 100 mg or more CRN-International ILSI Mexico, 8 June

16 Basic Approaches to Vitamin and Minerals Maximums 1. Risk assessment to establish UL (or HOI) 2. Determination of whether the UL or HOI is: a. Derived from total intake b. Identified from supplemental intake c. Includes fortified food intake 3. Identification of maximums for different products and population groups CRN-International ILSI Mexico, 8 June

17 WHY NOT RDA-BASED MAXIMUMS? 1. Impossible for substances without RDA values 2. RDA are not defined or identified on basis of safety or risk 3. Not permitted for maximums in Codex guideline for vitamin and mineral food supplements (2005) 4. Not permitted in European Commission directives on food supplements and addition of nutrients to foods 5. Not included in FAO/WHO nutrient risk assessment report (2006) 6. Disproportionate restriction of fortified foods and supplements in comparison with numerous conventional (unfortified) foods CRN-International ILSI Mexico, 8 June

18 Valid Uses of RDA Advise consumers on amounts of nutrients needed for basic nutritional functions for most individuals Basis (denominator) for calculation of percentages on food or supplement labels In risk assessment calculation of a Population Safety Index for use in designing monitoring and labeling programs CRN-International ILSI Mexico, 8 June

19 Codex Guideline for Vitamin and Mineral Food Supplements Maximums 1. shall be set taking the following into account (a) ULs established by risk assessment (b) Intake from other dietary sources 2. When setting maximums according to Para 1, due account should be given to population reference intakes (PRI or RDA) but these values may not be the sole basis for the maximums CRN-International ILSI Mexico, 8 June

20 What is Due Account for the PRI(RDA)? 1. No government or official organization has defined or described due account 2. The Codex guideline does not allow PRI values to be the sole basis of Maximums 3. EHPM-ERNA risk management model gives a reasonable meaning for due account 4. Maximum = UL (or HOI) Intake 5. Use of PRI: Population Safety Index = (UL Intake) PRI (Nutrients with low PSI need careful regulation) CRN-International ILSI Mexico, 8 June

21 EHPM-ERNA Model Population Safety Index = (UL MHI F+W ) Similar to Therapeutic Index for Drugs Three possible categories A, B and C PRI A. Vitamins or minerals with high PSI have a wide margin of safety above current intakes and may not require any regulatory limit for consumer safety B. Intermediate PSI nutrients can be managed with monitoring and/or label information C. Low PSI may require specific limits for consumer safety CRN-International ILSI Mexico, 8 June

22 Maximums for Nutrients in Food Products 1. Risk assessment to establish UL (or HOI) 2. Determination of whether the UL (or HOI) is: a. Foods b. Supplements 3. Identification of maximums for different products and population groups 4. Divide safe increases between fortification and supplementation CRN-International ILSI Mexico, 8 June

23 Fortified Foods and Supplements Fortified Foods Manufactured to concentration (amount per 100 g or 100 kcal) Can supply nutrients without consumer knowledge and cooperation Supplements Manufactured and labeled to contain an amount Consumer knowledge and control of level of consumption CRN-International ILSI Mexico, 8 June

24 Maximums for Fortification and Supplementation Two possibilities 1. Consider fortified foods and supplements together a) Identify UL Intake b) Allocate this difference between foods and supplements (50:50? Other? Rationale?) 2. Separately regulate fortification and supplementation CRN-International ILSI Mexico, 8 June

25 Rationale for Separate Regulation of Maximums Nutrients with potential risk due to small margin between usual intake and UL o o Caution with fortification due to lack of choice for consumer Consumer awareness can limit supplement intake Nutrients with low risk due to large margin between usual intake and UL o o Fortified foods and supplement present little risk No need for combined regulation CRN-International ILSI Mexico, 8 June

26 Contact Information John Hathcock, Ph.D direct fax CRN-International ILSI Mexico, 8 June