Implementing food-based dietary guidelines for - United Nations ...

Setting upper levels for nutrient risk assessment
particularly but not exclusively during risk management.
It is important that managers, the public, and
other stakeholders understand the assessment, and
it is envisaged that the entire process of risk analysis
should be open and transparent and that the views of
stakeholders should be taken into account as part of
the process.
Nutrient risk assessment: Applying the risk
assessment model
A joint FAO/WHO Technical Workshop [1] recently
reviewed the terms of reference and nutrient risk
assessments of three authoritative advisory reports,
namely, the European Food Safety Authority [13] for
the European Union, the Expert Group on Vitamins
and Minerals for the Food Standards Agency in the
United Kingdom [14], and the Institute of Medicine
of the National Academies for the United States and
Canada [15]. It is evident that these nutrient risk
assessments did not always find it easy to derive a UL
confidently. The groups often used the same data, and
there were many commonalities in their risk assessments.
However, the data are of an inconsistent and
uncertain quality, and there were differences in the use
made of the data, the derived ULs, and the expression
of the uncertainties. With such a predicament, there is
a need, both for public health considerations and for
harmonized approaches to regulatory issues in global
trade, to have an internationally agreed approach to
setting ULs that would serve as a basis for international
collaborative nutrient risk assessment, for the identification
and prioritization of knowledge needs, and for
organizing the necessary research.
The established toxicologic approach when applied
systematically to nutrient risk assessment reveals the
inherent limitations of the available data. In the United
Kingdom, for instance, in some cases the data were
felt to be too insecure to set safe ULs, and provisional
levels called guidance values (not to be confused with
health-based guidance values) were set instead. These
uncertainties include difficulties in identifying critical
adverse health effects; difficulties in extrapolating
between species and population age and gender groups;
a lack of confidence in the estimates of intakes (exposures)
involved with particular adverse health effects;
and no good, if any, dose–response data. Usually nutrient
risk assessment or, specifically, nutrient hazard
characterization has used the NOAEL and LOAEL
approach to develop a UL, and doing this with such
poor-quality data has meant using many uncertainty
factors. The application of the default values for these
uncertainty factors can result in such a large value that
when they are applied to a NOAEL or a LOAEL, they
produce health-based guidance values that are close to
or even below the upper end of the range for reference
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values for nutrient intakes. This “nutrient paradox” in
nutrient safety assessment is well recognized for minerals
but can be demonstrated also for organic nutrients
(e.g., ascorbic acid) [1]. The reasonable response of
risk assessors to this problem has been to reduce the
uncertainty factor values applied in deriving the UL.
Although this is done openly, the pathophysiological
basis of such flexibility is not necessarily easy to
explain.
Apart from the paucity of the database, the major
source of uncertainty in the risk assessment of nutrients
is the nature of the nutrients themselves. For non-nutrient
chemicals, the assumptions of risk assessment are
that they have no physiological role, have detoxification
pathways that are probably not chemical-specific, generally
have no interdependence on exposure to other
chemicals or nutrients, and do not increase the risk of
any adverse health effects at low intakes [1, 11]. Nutrients
are different; they have distinctive biochemical
and physiological roles, and biological organisms have
evolved specific and selective mechanisms to acquire,
absorb, distribute systemically, metabolize, and control
the body burden of the nutrient itself or its metabolites.
These homeostatic mechanisms respond to excursions
of intakes above or below physiological requirements.
As a result, nutrients have a dual–dose response curve,
i.e., there are adverse health effects at levels of intake
that, relative to systemic requirements, are inappropriately
high and at intakes that are inappropriately low
(fig. 2) [1, 2, 11]. Furthermore, the shape or inflexions
of the dose–response curve at the thresholds of excessive
and deficient intakes will be contingent on the
efficiency of the mechanisms of homeostasis and, possibly,
on the nutrient’s interdependence on the supply
and metabolism of other nutrients (e.g., the relatively
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FIG. 2. The dual biological, or U-shaped, response curve to
increasing oral intakes of a nutrient as applied to a population.
At low intakes, there is a cumulative risk of deficiency
that reflects the distribution of requirements, and at the upper
range of intakes there is a similar cumulative risk of toxicity.
Conceptually, the acceptable range of intakes represents a
zone bounded at points A and B within which homeostasis
ensures that intakes are used to meet individuals’ systemic
requirements. Source: International Programme on Chemical
Safety [2]
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