3. TOXICOKINETICS
3.1. ABSORPTION
3.1.1. Gastrointestinal Absorption
Barium sulfate is commonly administered to humans as a radiopaque contrast compound
to visualize the digestive tract. Despite its common use as a contrast material, human data on the
gastrointestinal absorption of barium sulfate and other barium compounds are limited. In a mass
balance study conducted by Lisk et al. (1988), one man consumed a single dose of 179 mg Ba
from 92 g of Brazil nuts and it was estimated that at least 91% of the dose was absorbed. In an
unpublished doctoral dissertation (Bligh, 1960), the absorption of orally administered
140
barium
and
45
calcium was reported for five female cancer patients. Mean and standard deviation of the
calculated absorption for barium was 9 ± 6%.
Reported absorption of barium in animal studies ranges from less than 1% to greater than
80%. Taylor et al. (1962) reported gastrointestinal absorption for a single gavage dose of
133
BaCl
2
in older (6-70 weeks of age) nonfasted rats to be 7%-8%, compared to 20% in older
fasted animals, and 63%-84% in younger (14-22 days) nonfasted rats.
These data suggest that
both age and feeding status affect the absorption of barium. In 30-day retention studies
conducted by Della Rosa et al. (1967) and Cuddihy and Griffith (1972), the reported
gastrointestinal absorption in adult dogs was 0.7%-1.5% and
#
7% in younger dogs (43-250 days
of age).
McCauley and Washington (1983) and Stoewsand et al. (1988) compared absorption
efficiencies of several barium compounds.
131
Ba-labeled barium sulfate and barium chloride
were absorbed at “nearly equivalent rates” (based on blood and tissue levels) in rats following
single gavage doses of the compounds each equaling 10mg barium (McCauley and Washington,
1983). Similar concentrations of barium were found in the bones of rats fed diets with
equivalent doses of barium chloride or barium from Brazil nuts. McCauley and Washington
(1983) suggested that the similarity in absorption efficiency between barium sulfate and barium
chloride may have been due to the ability of hydrochloric acid in the stomach to solubilize small
quantities of barium sulfate. This is supported by the finding that barium carbonate in a vehicle
containing sodium bicarbonate was poorly absorbed. The buffering capacity of sodium
bicarbonate may have impaired the hydrochloric acid-mediated conversion to barium chloride.
The results of these studies suggest that soluble barium compounds or barium compounds that
6
yield a dissociated barium ion in the acid environment of the upper gastrointestinal tract have
similar absorption efficiencies.
Barium sulfate is often considered to be very poorly absorbed. The results of the
McCauley and Washington (1983) study provide evidence that at low concentrations the
absorption of barium sulfate is similar to barium chloride. High concentrations of barium sulfate
are likely to exceed the ability of the gastric hydrochloric acid to liberate significant amounts of
barium ions from barium sulfate. However, some of the barium sulfate will still be absorbed.
Statistically significant increases in the levels of barium in the blood and urine have been
reported in humans ingesting 58 to 400 g barium sulfate in radiopaque contrast materials (Claval
et al., 1987; Mauras et al., 1983).
3.1.2. Respiratory Tract Absorption
No data are available on respiratory tract absorption of barium in humans. Animal
studies provide evidence that barium compounds, including poorly water-soluble compounds
such as barium sulfate, are absorbed from the respiratory tract. Morrow et al. (1964) estimated
that the biological half-time of
131
BaSO
4
in the lower respiratory tract was 8 days in dogs
inhaling 1.1
:
g/L barium sulfate (count median diameter [CMD] of 0.10
:
m,
F
g
of 1.68) for 30
90 min. Twenty-four hours after an intratracheal injection of
133
BaSO
4
, 15.3% of the
radioactivity was cleared from the lungs. The barium sulfate was cleared via mucociliary
clearance mechanisms (7.9% of initial radioactive burden) and via lung-to-blood transfer (7.4%
of radioactivity) (Spritzer and Watson, 1964). Clearance half-times of 66 and 88 days were
calculated for the cranial and caudal regions of the trachea in rats intratracheally administered 2
:
g
133
BaSO
4
(CMD of 0.34
:
m,
F
g
of 1.7) (Takahashi and Patrick, 1987).
Differences in water solubility appear to account for observed differences in respiratory
tract clearance rates for barium compounds. The clearance half-times of several barium
compounds were proportional to solubility in dogs exposed to aerosols of barium chloride
(activity median aerodynamic diameter [AMAD] of 2.3
:
m,
F
g
of 1.5), barium sulfate (AMAD
of 1.0
:
m,
F
g
of 1.6), heat-treated barium sulfate (AMAD of 0.9
:
m,
F
g
of 1.4), or barium
incorporated in fused montmorillonite clay particles (AMAD of 2.2
:
m,
F
g
of 1.7) (Cuddihy et
al., 1974).
3.1.3. Dermal Absorption
No data are available on dermal absorption of barium compounds.
7