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Criteria completely described?


exposure (low doses over a long period of time) is preferable. Extrapolation of long- term effects from short-term studies increases the level of uncertainty.

5. Were the criteria for characterizing responses clearly described?

This information is needed to evaluate the relevance of the response measured. A definitive diagnostic assessment showing clinical signs or intestinal mucosal changes compared to controls is preferred.

6. Are response data available for each individual tested?

These data are needed to develop a risk assessment-based dose-response model.

2. Options and Findings The feasibility of using each of the four methods to establish a threshold for gluten was evaluated in light of the available data. As with food allergens, it is likely there will be significant scientific advances in the near future that will address a number of the limitations identified in this report. The Threshold Working Group was aware of several potentially important studies that are currently in progress, but we were unable to evaluate them because the data or analyses are incomplete.

In particular, the Threshold Working Group is aware of unpublished data from an ongoing clinical trial of the subchronic effects of gluten on celiac patients. The “Italian Microchallenge Study” is utilizing intestinal biopsies to relate changes in the intestinal mucosa to antibody biomarkers (Fasano, 2005 personal communication). Preliminary results indicate that daily consumption of both 10 mg and 50 mg of dietary gluten were well tolerated after three months of continuous consumption, but that minimal histological changes were seen in patients consuming 50 mg of gluten daily. Because these data have not yet been published, these results were not considered further.

Finding 6. The initial approach selected to establish a threshold for gluten, the threshold value selected, and any uncertainty factors that were used to establish the threshold should be reviewed and reconsidered periodically in light of new scientific knowledge and clinical findings.

a. Analytical Methods-Based Approach. As with food allergens, an analytical methods-based approach could be used to establish a threshold for gluten if the available clinical and epidemiological data are insufficient to use one of the other approaches. This approach requires that analytical methods be available to detect all relevant glutens. Thresholds are defined by the limits of detection of the available analytical methods, but there is no relationship between these thresholds and the biological response thresholds. At the time of this report, the lower limits of detection for the commercially available gluten test kits are in the range of 10 µg gluten/g of food, and the ability to robustly quantify samples is in the range of 20 µg gluten/g of food. Establishing thresholds at levels higher than the lower detection limits of the analytical methods requires the use of

Revised Threshold Report Page 61 of 108

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