Lead - Toxicology of Metals - page 597

Lead concentration in urine has been used widely
for biomonitoring (Section 2.6.1.3).

been developed (Goodrum et al ., 1996). The use of a
high gastrointestinal absorption rate (40-50%, even at
age 7) has been criticized (Gulson et al ., 1997).
Another model of lead kinetics has been developed
and validated for adults with a wide range of expo-
sures from a variety of sources (O'Flaherty, 1993). It
has been supplemented with a probabilistic module
(Beck et al ., 2001). The model has been tested in chil-
dren (O'Flaherty, 1995) and lead workers (Fleming
et al ., 1999). Both B-Pb and bone lead are very labile
in early childhood; they respond rapidly to increases
in exposure, and decrease almost as rapidly to near-
preexposure concentrations when exposure returns to
background levels. From the peak in adolescence and
into early adulthood, the rate of bone turnover drops
dramatically, and, hence, the ability to reverse bone-
lead accumulation rapidly decreases.
Despite some qualitative and quantitative differ-
ences in lead uptake, the O'Flaherty (1993 and 1995)
and IEUBK (U.S. EPA, 1994) models give predictions of
B-Pb that are not greatly dissimilar (O'Flaherty, 1998).
After a rise of the exposure intensity, the B-Pb
increases gradually, usually to reach a steady state after
weeks to months (Christoffersson et al ., 1984). How-
ever, after a heavy inhalation exposure, the B-Pb may
rise by fi ve times aleady within a few hours (Schütz
and Skerfving, 1976).
After a decrease of exposure, there is a decay of
B-Pb concentrations, which shows several components
(Figure 7). In adults, the decline rate is compatible
with an initial phase with a half-time of approxi-
mately 1 month, if slow phases are taken into consid-
eration (Nilsson et al ., 1991; Rabinowitz et al ., 1977;
Schütz et al ., 1987b). The interindividual variation is
large. There are some indications that the rate may
be slower in infancy (Ryu et al ., 1978), at older age
(Hryhorczuk et al ., 1985; Schütz et al ., 1987b), and in
subjects with renal impairment (Hryhorczuk et al .,
1985). During CaNaEDTA treatment, the half-time
is approximately 1 week (Hryhorczuk et al ., 1985),
in combination with hemodialysis only a few hours
(Martegani et al ., 1989).
Slow phases of lead elimination from blood refl ect
elimination of bone pools. Again, there is an interindi-
vidual variation (Schütz et al ., 1987b). Lead is lost from
the bone by diffusion (heteroionic exchange), as well
as by resorption. The trabecular (spongy, e.g., in cal-
caneus, patella, and vertebrae) bone lead has a more
rapid turnover than the cortical (Schütz et al ., 1987a).
From analyses of B-Pb elimination curves, the half-time
in trabecular bone was estimated at approximately 1
year (Nilsson et al ., 1991). On the other hand, by XRF
measurements, the half-times in the mainly trabecu-
lar calcaneus (Gerhardsson et al ., 1992; Hu et al ., 1998),

2.5.4.2 Gastrointestinal Tract
Lead is also excreted through bile (Ishihara and
Matsushiro, 1986) and pancreatic juice (Ishihara et al .,
1987) into the feces (Rabinowitz et al ., 1980). Possibly,
the excretion in bile is in the form of a lead-glutathione
complex (Alexander et al ., 1986).

2.5.4.3 Other Routes of Elimination
Lead is also, to some extent, excreted in saliva (Koh
et al ., 2003) and sweat (Kehoe, 1987; Omokhodion and
Cockford, 1991; Rabinowitz et al ., 1977). Amounts
without practical importance (besides, possibly, for
biological monitoring; Section 2.6.1.4) are excreted in
nails and hair (Foo et al ., 1993; Rabinowitz et al ., 1977).
Lead is also incorporated into semen, the placenta,
the fetus, and milk (Section 2.11).

2.5.5 Biokinetics

The toxicokinetics of lead may be described by com-
partment (U.S. EPA, 1994; Skerfving et al ., 1995) and
physiologically based pharmacokinetic (Legett, 1993;
O'Flaherty, 1993) models.
A simple compartment model is presented in Figure
3. There are very fast (blood plasma), rather fast (blood
cells and soft tissues), and slow (skeleton) compart-
ments. The U.S. Environmental Protection Agency has
designed an “Integrated Exposure Uptake Biokinetic
Model for Lead in Children” (IEUBK), a detailed, clas-
sical compartment model (U.S. EPA, 1994; 2002; White
et al ., 1998). In a four-step process, it mathematically
and statistically links several sources (soil, house dust,
drinking water, air, and food) of environmental lead
exposure to distributions of B-Pbs in populations of
children, 0-84 months of age. It takes into account
indoor and outdoor air lead, time spent outdoors, ven-
tilation rate, and lung absorption. The gastrointestinal
bioavailability is expressed in relation to lead acetate in
pigs. The in utero transfer is estimated from maternal
B-Pb. The body compartments are lungs, gastrointes-
tinal tract, plasma/extracellular fl uid, red blood cells,
kidney, liver, other soft tissues, and trabecular and cor-
tical bone. The elimination occurs through urine, feces,
and skin/hair/nails. The transfer rates are based in
part on kinetic data in baboons. Certain nonlinearities,
specifi cally capacity-limited binding in the red cell and
absorption from the gastrointestinal tract, are built into
the model.
The accuracy of the model in prediction of B-Pb has
been verifi ed (Choudhury et al ., 1992). Furthermore,
a probabilistic (of exposure parameters) version has