Chemistry Reference
In-Depth Information
from the metallothionein fraction in plasma. A very
minor part of B
3
(approximately 5%) is transferred to
the urine. Because renal tubular reabsorptive capacity
diminishes with age, C
17
is partly age dependent.
The fl ow of cadmium among the compartments in
the model described by Kjellstrom and Nordberg was
derived by a series of equations. An improved mathe-
matical approach that uses the same model for Cd fl ow
in the human body (Figure 17), has been described
by Choudhury
et al.
(2001). The equations describing
intercompartmental transfers of Cd were implemented
as differential equations in Advanced Continuous Sim-
ulation Language (ASCL v 11), and improved growth
algorithms and other adjustments were used. A Monte
Carlo simulation was used to propagate variability in
daily intake through the model. On the basis of data
concerning intake of Cd in the US population, levels
of Cd in urine in the US population were computed by
this model. When comparing their results with those
measured in NHANES II, they found good agreement
in men as shown in Figure 17, whereas the urine Cd
values in women generated by the model were lower
than those observed in NHANES II. Data demonstrat-
ing a higher gastrointestinal absorption in women than
men have been published since the Kjellstrom-Nord-
berg model was developed in the 1970s. This informa-
tion was used and gastrointestinal uptake in women
was adjusted to 10% (instead of 5% in both men and
women originally used by Kjellstrom and Nordberg).
With this modifi cation, Choudhury
et al.
(2001), found
reasonably good agreement between observed and
model generated values in females also.
6.2.2 Use of Multicompartment and Physiologically
Based Models for TK/TD Modeling
Toxicokinetic (TK)—toxicodynamic (TD) modeling
describe quantitative estimations of expected dose-
response relationships by the use of TK/TD data. Early
contributions to this fi eld that used data on cadmium
were those published by Nordberg and Strangert (1985),
described and discussed in more detail in Chapter 23.
More recently, multicompartment (IEUBK model) and
physiologically based models (e.g., O'Flaherty, 1993)
have been used to assist in risk assessment of metal
exposures in humans, but published estimates of
expected dose-response relationships are not available.
7 USE OF INDICATOR MEDIA FOR
ESTIMATION OF EXPOSURE OR CRITICAL
ORGAN CONCENTRATION
To estimate the risk of poisoning for an individual or
a group of individuals, it would be desirable to meas-
ure the dose at the site of effect (i.e., the concentration in
Urinary cadmium - males
0.5
CDEM
NHANES
0.4
0.3
0.2
0.1
0.0
0
10
20
30
40
50
60
70
Age (yr)
FIGURE 17
Urine levels of Cd in relation to age in the US population and a comparison with values
calculated by Choudhury
et al.
(2001).
