Outcome of the EFSA-workshop on tolerable upper intake levels 

Jan 28, 2022 | Regulatory

In the autumn of last year, a workshop was held to discuss the conceptual and methodological principles relevant to the revision of the EFSA guidance document on the development of tolerable upper intake levels (ULs) for vitamins and minerals. The outcome of the workshop can be summarized as follows:

  • The current definiton and interpretation of ULs were declared appropriate and sufficient for the application in risk assessment and risk management purposes.
  • Overall it was commonly agreed that the corresponding target population is defined as “general population”.
  • Another question dealt with the establishment of an alternative value if the data are not sufficient for the determination of an UL. It was considered important to provide some kind of intake level for the risk characterization, particulary for nutrients with evidence of adverse health effects. The use of an alternative value may be more limited than that of an UL due to great uncertainties but could be used as a conservative value that provides at least a reference point for risk management decisions.
  • With regard to biological based models and the use of biomarkers, it was concluded that expert judgement is required, since adverse (health) effects from excessive intake of a nutrient may cover a very broad range of health risks. The selection of suitable biomarkers proves to be complicated, however, biomarkes could reduce the magnitude or even need of an uncertainty factor. To establish the relationship between a potential biomarker and the adverse health endpoint, all available information should be used, including mechanistic evidence of biological plausibility. 
  • The dose-response modelling is considered a usefull and desirable alternative to the NOAEL approach, but available data may be a limiting factor. As a possible concept, the Benchmark Dose (BMD) approach could be used for nutrients. In any case, flexibility is required in the choice of the modelling method, because each modelling has specific uncertainties.
  • In addition, it was discussed how chronic disease risks should be integrated in the UL evaluation. First of all, the definition of adverse helath effects should be revised, as there were discrepancies. There were divergent opinions on whether separate values should be derived on the basis of chronic disease endpoints; most participants opposed the use of a different term for the upper level derived from chronic diseases. However, there are significant differences in the interpretation of UL and upper limits based on chronic diseases. 

For more details, please refer to the outcome report of the workshop.

As a result, the guidance of the SCF (Scientific Committee on Food) will be updated. The draft version of the guidance will be applied to EFSA’s assessments during a one-year pilot phase and revised and complemented if necessary.