Dietary Supplements Joint Committee Meeting May 20, 2007

1. Dietary SupplementsJoint CommitteeMeetingMay 20, 2007 Recommended Changes to Pass/Fail Criteria for Metal Contaminants Clif McLellan Director of Toxicology Services NSF International

2. Presentation Outline • Review ballot submitted to change pass/fail criteria for cadmium, chromium and lead Background of current criteria and reason for change • How were proposed criteria derived? • How are values calculated? • Current vs proposed levels • Impact of change for certified products

3. Background of current criteria and reason for change • The current pass/fail criteria were originally established in 2003. The criteria were chosen because; • it was felt that using international criteria would better reflect the international focus of this program. • No data were available indicating the level of metal contaminants that would be expected. • Since 2003, the program has developed more as a North American Standard and it is now believed that the basis of the pass/fail criteria should be more reflective of North American Standards and be based on health effects endpoints whenever possible.

4. How were proposed criteria derived (cadmium, chromium and lead)? • A review was performed to determine the best human health risk assessment available for cadmium, chromium and lead. • For cadmium and chromium the U.S. EPA risk assessments were determined to be the most current and used state-of-the art risk assessment procedures.

5. How were proposed criteria set (Lead)? • Since there is no current safe level set for lead an alternate approach was required which met the following criteria; • as low as was achievable based on current test results • be more protective of sensitive sub populations (children and pregnant women).

6. How are the criteria calculated based on daily safe levels?Finished Product Criteria Rfd (mg metal /kg-bw-day) * 60 kg-bw * RSC --- mg metal / day RSC = Relative Source Contribution = 0.1 (10% of daily acceptable level). Lab evaluation Lab result (mg metal / g product) * maximum recommended daily dose (g product / day) ---- mg metal /day

7. How are the criteria calculated based on daily safe levels?Raw Ingredient Criteria Rfd (mg metal /kg-bw-day) * 60 kg-bw * RSC * 1/AUL * Unit conversion --- ug metal / g ingredient --- ppm RSC = Relative Source Contribution = 0.1 (10% of daily acceptable level) AUL = Assumed Use Level = 1000 mg ingredient Unit Conversion = 106 ug metal / 1g metal * Raw ingredients can be evaluated based upon a use level recommended by manufacturer Lab evaluation Lab result (ug metal / g ingredient) ---- ppm

8. What other levels have been established (units - ug/day)?

9. Raw Materials - Current vs Proposed Levels 5.3.1.1 Raw materials – Current Raw materials shall not contain undeclared metals in amounts greater than the following: – cadmium content shall not exceed 0.3 ppm; – chromium (VI) content shall not exceed 2 ppm; – lead content shall not exceed 10 ppm; and 5.3.1.1 Raw materials – Proposed Raw materials shall not contain undeclared inorganic metals in amounts greater than the following: – cadmium content shall not exceed 4.1 ppm; – chromium (VI) content shall not exceed 20 ppm; – lead content shall not exceed 15 ppm; and

10. Finished Products - Current vs Proposed Levels 5.3.1.2 Finished products – Current Finished products shall not contain undeclared metals at rates of intake greater than the following: – cadmium content shall not exceed 0.006 mg/d; – chromium (VI) content shall not exceed 0.02 mg/d; – lead content shall not exceed 0.02 mg/d; 5.3.1.2 Finished products - Proposed Finished products shall not contain undeclared inorganic metals at rates of intake greater than the following: – cadmium content shall not exceed 0.0041 mg/d; – chromium (VI) content shall not exceed 0.02 mg/d; – lead content in products marketed for children or women shall not exceed 0.0005 mg/d; – lead content in all other products shall not exceed 0.015 mg/d; and

11. Requested Action? Ballot proposed levels for adoption to Dietary Supplement Standard for inorganic cadmium, chromium VI and lead

12. Basis for Current Criteria

13. Relative Source Contribution • Definition: A factor that is used to proportion the total acceptable level of a contaminant for a single source of exposure. • If a proportion of the acceptable level for a contaminant is not considered, the compounding of exposure from various sources would result in an unacceptable daily exposure. • Sources of exposure to consider: oral, dermal or inhalation. • For oral exposure consideration would be for water, food (various types) and supplements. • Example default source contributions are food (80%) and water (20%) when air sources are known to be minimal or insignificant.

14. Source Contribution - How could you determine a source contribution for dietary supplements for a contaminant as a proportion of total daily exposure? • Weight? • Example: 2 g DS / 3 kg food +2 kg water = 0.04 % • Volume? • Same result. • Base it on exposure levels, when known? • Subtract each known source of exposure from the “safe” level. • Safe level – oral – dermal – inhalation Limitations: would you use averages? 90, 95, 99 percentile? Which population(s)? Are data available? The “safe” level for heavy metals is either “0” or very low.

15. Source Contribution – Why did we use 10% ? • Most risk values are good to one significant figure (chromium, cadmium and mercury) and 10% of the daily total would result in a numerically insignificant exposure. • Other established source contributions are 80% food and 20% water, and we felt that dietary supplements should contribute less than the amount allowed for food and water while at the same time not be too restrictive. • Contaminant levels should be set so they provide protection based on human health endpoints.