Chemistry Reference
In-Depth Information
nutrients are usually not suitable for the derivation of a
BMD. The mathematical modeling used in the deriva-
tion of a BMD requires high-quality studies with multi-
ple intakes showing graded responses at different levels
of intake. Such studies on EMs in humans are usually
not available. Even animal studies that might be useful
in deriving the UL provide limited dose-response data.
Therefore, the UL for the AROI of EMs is presently based
on the use of NOAEL or LOAELs and the application
of appropriate UFs based on expert scientifi c judgement
(FAO/WHO, 2006; IOM, 1998; SCF, 2000a; WHO/IPCS,
2002). This risk assessment approach is necessitated
by the quality of data now available. However, it is
strongly recommended that research efforts be intensi-
fi ed to generate data on the toxicity of EMs that would
permit the application of the BMD model. As pointed
out by WHO/IPCS (2002), this approach provides a
more precise estimation of the UL, because it analyzes
the complete dose-response curve, including the confi -
dence interval around the central estimate. Although the
NOAEL/UF approach is a very useful risk assessment
tool, where adequate dose-response data are available,
the BMD model can decrease the level of uncertainty in
risk evaluations and is thus a preferable approach for
dose-response evaluation (WHO/IPCS, 2002). The BMD
approach for risk assessment of metals is discussed in
Chapter 14.
Although neither the USIOM/FNB nor the EU/SCF
used the term AROI, the recommendations for RDAs,
AI, and PRIs, when combined with the recommended
UL, is equivalent to the AROI described in Section
2 of this chapter. The method described by each of
these organizations follows the principles and steps
described in Section 4 of this chapter.
The derivation of a SRPMI (WHO, 1996) used many
of the steps described in this chapter, particularly the
use of a weight of evidence approach. It can be consid-
ered similar to an AROI but based on observations of
the distributions of population mean intakes and their
distribution. The difference in percentage of a partic-
ular population at risk from the choice of the SRPMI
compared with an AROI will be affected by the slope
(shape) of the relevant intake distributions and the
slope of the risk of toxicity or defi ciency curves. Theo-
retically, if the same criteria for safety are used for both
the SRPMI and the AROI, the SRPMI will cover a nar-
rower range of intakes; however, this difference may
be very small in practice as indicated in Table 3.
A summary of recommended intake ranges (consid-
ered here as AROIs) by the EU/SCF, USIOM/FNB, and
WHO for fi ve EMs in adult men is shown in Table 3.
In comparing these ranges it must be remembered
that the recommended intake for nutrition (RDA, AI,
PRI) represents the amount from dietary sources only,
whereas the UL and PMTDI represent the oral intake
from all sources (food, water, and supplements) (IOM,
2001; SCF, 1993). The SRPMI represents dietary intakes
only. However, when developing specifi c SRPMIs, it
was realized water and supplements might provide
added exposure that might result in toxicity. In those
cases, the upper boundary of the SRPMI was adjusted
to refl ect such exposures (WHO, 1996). Although val-
ues are given for adult men only, all three organiza-
tions developed recommendations for intakes by other
defi ned populations.
An examination of the intake ranges (considered
as AROIs) for any one of the fi ve EMs in Table 3 indi-
cates they are very similar, with a few signifi cant
TABLE 3
Comparison of Intake Recommendations for Five Essential Metals in Adult Males
from Europe
(a)
, North America
(b)
and WHO
(c)
SCF
IOM
WHO
Essential Metal
PRI
UL
RDA
UL
SRPMI
Copper (mg/day)
1.1
5
0.9
10
1.3-12
Iron (mg/day)
9
ND
8
45
ND (see note
(d)
)
Manganese (mg/day)
1-10
ND
2.3 (an AI)
11
ND
(a safe & acceptable range)
Selenium (ug/day)
55
300
55
400
40-400
Zinc (mg/day) (moderately available)
9.5
25
11
40
9.4-45
(a)
European Union Scientifi c Committee on Food [PRIs (SCF, 1993); manganese (SCF 2000b); selenium (SFC 2000c); copper (SCF 2003a);
zinc (SCF 2003b)].
(b)
United States Institute of Medicine/Food & Nutrition Board [selenium (IOM, 2000); copper, manganese & zinc (IOM 2001); DRI
summaries (IOM 2006)]
(c)
World Health Organization (WHO 1996)
(d)
FAO/WHO recommended a requirement of 9 mg Fe/day for an adult male (WHO/FAO 2002) and WHO (1983) calculated a PMTDI of
48 mg Fe/day (0.8 mg/kg bw). The range 9 to 48 can be considered as an AROI for iron in adult males.
AI = Adequate Intake
ND = Not determined
