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standard uncertainty factor of 10 might be applied for intraspecies differences in human responses to gluten.



Factor 10 10

Standard for intraspecies variability.

Standard if NOAEL data not available. Supported by clinical trial data.

Table IV-10. Examples of Uncertainty Factors for the Safety Assessment-Based

Approach. Description

Intraspecies difference1

Extrapolation from LOAEL 2

3 Chronic, low-level gluten exposure


Estimate using data from gluten clinical trials.

Overall Uncertainty Factor4 = 600

1 2 This includes both between- and within-individual variability. This includes both a factor for converting the LOAEL to a NOAEL and an additional factor for the uncertainty associated with that conversion factor. Preliminary NOAEL data from an unpublished clinical trial (Fasano, 2005 personal communication) support an approximate 10-fold difference between a NOAEL and published LOAELs (Catassi et al., 1993).

3 Estimated by comparing published LOAELs in an acute, single dose exposure (Ciclitira et al., 1984) with repeated exposure over four weeks (Catassi et al., 1993).


Uncertainty is likely to decrease as clinical trial data become available.

Finding 8. The safety assessment-based approach is a viable approach to establish a threshold for gluten using currently available LOAEL data for celiac disease. An overall uncertainty factor should be estimated from the data and applied to the LOAEL to establish a threshold for gluten. Any threshold derived from this approach should be reevaluated as new research data become available. Available data are insufficient at the current time to use this approach to establish a threshold for oat gluten for those individuals with celiac disease who may also be sensitive to oats. However, it is likely that a threshold based on wheat gluten would be protective for individuals susceptible to oat gluten.

c. Risk Assessment-Based Approach. There are few data from human clinical trials that can be used to develop a dose-response model for gluten and celiac disease. In addition, limited data are available on exposure; for example, there are limited data on the actual levels of gluten in the diet of individuals on “gluten-free diets” and on the effects of low-level, chronic gluten exposure in individuals with silent or latent celiac disease. These limitations would lead to a very high level of uncertainty associated with models designed to predict the health effects of gluten in the diet. Therefore, a scientifically defensible hazard characterization and exposure assessment are not possible at the current time.

Finding 9. Use of the quantitative risk assessment-based approach to establish a threshold for gluten does not appear to be feasible at the present time. However, considering the benefits that could be gained from using the risk assessment-based

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