Chemistry Reference
In-Depth Information
The “permissible values” for rice Cd concentrations,
lifetime Cd intake, and urinary Cd concentrations
(cited in the foregoing text) are all low and do not dif-
fer appreciably from the degree of Cd exposure in the
general environment. This situation is supported by
the reported benchmark doses and lower confi dence
limits of the benchmark dose (LBMD) of Cd in urine
giving rise to tubular dysfunction in Chinese popu-
lation groups exposed to Cd (Jin
et al
., 2004). In that
study, the authors reported LBMD values (correspond-
ing to the lower confi dence limit of PCC-5) for UCd to
be 3-4
cator has been used widely in epidemiological studies
(referred to in the foregoing text), and it is known to
be of importance for health (cf. Section 9). Our quan-
titative evaluation is similar to the one presented by
Jarup
et al
. (1998c), but we specify the dose-response
relationship (Table 7) as
β
2
-microglobulinuria above
the normal range (i.e., above approximately 300
g/g
CR), whereas Jarup
et al
. (1998c) used B2M and other
indicators, such as NAG, as the basis for their assess-
ment of “tubular effects.”
In adult nonsmokers having a body weight of 70 kg,
an average daily intake of 30
µ
g/g CR when using bioindicators of renal dys-
function, such as NAG, NAG-B,
µ
g Cd over a lifetime
(implying that only a small proportion of persons in
a population will exceed 50
µ
β
2
-microglobulin, and
RBP. The background levels of urinary Cd in the control
group were relatively high, and only 64 of the 790 sub-
jects in this study had UCd levels < 1
g/g in the kidney cor-
tex) will increase the degree of renal dysfunction by
approximately 1% (
µ
g/g CR; these
features may have infl uenced the calculated LBMD
values upwards (cf. the discussion in Chapter 14).
Chen
et al
. (2006a) studied an occupationally Cd-
exposed group in China and found that the LBMD for
metallothioneinuria was 3.1
µ
β
2
-microglobulinuria). In high-risk
groups, such as females with depleted iron stores, dia-
betics, or subjects with increased levels of MT antibod-
ies, a considerably higher percentage is expected to
display such an effect.
If exposed at the present PTWI, corresponding to
µ
g/g CR and for urinary
NAG 2.7
g/g CR. In a study by Uno
et al
. (2005), even
lower benchmark doses were reported in Japanese
population groups.
The Joint FAO/WHO Expert Committee on Food
Additives (WHO/FAO, 2003; 2005) has set the provi-
sional tolerable weekly intake (PTWI) of Cd at 7
µ
70
g/day from food, approximately 7% of the popula-
tion will be expected to develop tubular dysfunction;
the fi gure for the at-risk groups will be higher.
Dietary intake of Cd has been estimated to be
10-50
µ
g/kg body weight) on aver-
age in various countries (see Section 4.1.1) These
intakes are all below the present PTWI of 7
µ
g/day (0.13-0.84
µ
µ
g/kg
body weight. This value corresponds to 1
µ
g/kg body
µ
g/kg body
weight for each day of the week (i.e., 70
µ
g/day for a
weight, corresponding to 1
µ
g/kg body weight/day or
person of 70-kg body weight).
The PTWI is set to allow a certain variation of intake
during a week, provided that the weekly intake is not
exceeded. Because the critical effect of long-term oral
intake is renal dysfunction, short-term exceedances
can, in principle, be accepted. The extent to which
excursions above the PTWI can be allowed during var-
ious time intervals was discussed by Nordberg (1999).
Oral intake of Cd in a high single dose from food or
drink gives rise to gastrointestinal symptoms (see Sec-
tion 7.1). A single oral dose of 4-14
70
g/day for a 70-kg person. Some people do, how-
ever, exceed a level of 30
µ
g/day for an adult person
(discussed in the foregoing text), and it is likely that
some adverse effects on the kidneys do occur in par-
ticularly sensitive people in some populations of the
world. Recently reported data from the general pop-
ulations cited in the foregoing text indicate effects at
internal Cd doses lower than those used in this risk
characterization. The present assessment was per-
formed in relation to an increase in
µ
β
2
-microglobulin
excretion. Increases in more sensitive biomarkers of
renal tubular effects (i.e., prot HC, NAG, and CC16)
have been reported in some general population groups
at Cd levels in urine <2.5
µ
g/kg body weight
or a dose of 3
g/kg body weight during periods of
months was considered tolerable by adult persons
without the appearance of gastrointestinal symptoms
when PTWI is temporarily exceeded. To avoid the risk
of renal dysfunction, there should be a period of com-
pensatory intakes lower than the PTWI. For children
and pregnant or lactating women, daily intakes should
not exceed 1
µ
g/g CR. In diabetics, peo-
ple with increased levels of MT antibodies, or people
coexposed to other nephrotoxic substances, tubular
dysfunction has been reported at even lower Cd levels
(Chen
et al
., 2006b; 2006c).
Recent reports indicate the possibility that renal
dysfunction may occur in diabetics and in children at
urinary Cd levels of 0.5-1.0
µ
g/kg body weight in view of potential
adverse effects in the offspring, as indicated in animal
experiments (see Section 7.2.8).
Our risk characterization of Cd exposure in the gen-
eral population, on the basis of presently available data,
uses increased urinary excretion of
µ
g/g CR, but these obser-
vations require further confi rmation. When there is
simultaneous exposure to other nephrotoxic agents,
renal dysfunction can occur at these, or lower, urinary
Cd levels.
µ
β
2
-microglobulin as
the criterion for renal tubular dysfunction. This indi-
