Food Safety 341Food Additives and Contaminants (JECFA) or Joint
Meeting on Pesticide Residues (JMPR), both jointly
organized by the WHO and FAO. These expert groups
advise on acceptable or tolerable levels of intake of
these substances.
Acceptable and tolerable levels of intake
The acceptable daily intake (ADI) level of a chemical
is the daily intake that, during a lifetime, would pose
no appreciable risk to the consumer, on the basis of
all facts known at the time. It is expressed in mg/kg
of body weight (Box 14.2).
The tolerable weekly intake (TWI) represents per-
missible human weekly exposure to those contami-
nants unavoidably associated with the consumption
of otherwise wholesome and nutritious foods. The
term tolerable signifi es permissibility rather than
acceptability for the intake of contaminants that have
no necessary function in food, in contrast to those of
permitted pesticides or food additives. For cumulative
toxicants, such as lead, cadmium, and mercury, the
tolerable intakes are expressed on a weekly basis
to allow for daily variations in intake levels, the
real concern being long-term exposure to the
contaminant.
The maximum tolerable daily intake (MTDI) has
been established for food contaminants that are not
known to accumulate in the body, such as tin, arsenic,
and styrene. The value assigned to the provisional
MTDI represents permissible human exposure as a
result of the natural occurrence of the substance in
food and drinking water.
One of the most diffi cult issues in food safety is
to advise on the potential risks to human health for
substances found in food which are both genotoxic
(damaging DNA, the genetic material of cells) and
carcinogenic (leading to cancer). For these substances,
it is generally assumed that even a small dose can have
an effect. JECFA addressed this issue in 1978 and
introduced the concept of an “irreducible level,” which
it defi ned as “that concentration of a substance which
cannot be eliminated from a food without involving
the discarding of that food altogether, severely com-
promising the ultimate availability of major food sup-
plies” (FAO/WHO, 1978).
Until now the risk assessors have advised to keep
the exposure to such substances at the lowest possible
level. This approach is known as the ALARA principle
(“as low as reasonably achievable”). A disadvantage of
this approach is that it cannot be used to compare
risks posed by different substances. Furthermore, the
application of the ALARA principle does not take into
account the effectiveness of a substance and the actual
(sometimes extremely low) level of occurrence in
food.
A different approach, “the margin of exposure”
(MoE) approach, which can be used to assess the risks
to human health of exposure to a substance in the
absence of a tolerable daily intake or similar guidance
value, has recently been endorsed by the EFSA Scien-
tifi c Committee (EFSA, 2005) and the WHO/FAO
Joint Expert Committee on Food Additives (WHO/
FAO, 2005). The margin of exposure is defi ned as the
reference point on the dose–response curve (usually
based on animal experiments in the absence of human
data) divided by the estimated intake by humans. It
enables the comparison of the risks posed by different
genotoxic and carcinogenic substances. Differences in
potency of the substances concerned and consump-
tion patterns in the population are taken into account
when applying the MoE approach.Setting the acceptable daily intake
JECFA generally sets the ADI of a substance on the
basis of the highest no-observed-effect level in animal
studies. In calculating the ADI, a “safety factor” is
applied to the no-observed-effect level to provide a
conservative margin of safety on account of the inher-Box 14.2 Levels of intake of a chemicalNo observed effect Greatest concentration or amount of an
level (NOEL) agent, found by study or observation,
↓ that causes no detectable, usually
adverse, alteration of morphology,
functional capacity, growth,
development, or lifespan of the target
/Safety factor Uncertainty factor for extrapolating
↓ animal data to humans
/Safety factor Human interspecies variation
↓
Acceptable daily Daily intake that, during a lifetime,
intake (ADI) would pose no appreciable risk to the
consumer, on the basis of all facts
known at the time. It is expressed in
mg/kg of body weight