Concise International Chemical Assessment Document 33
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11.1.2
Criteria for setting tolerable intakes/
concentrations or guidance values for
barium and barium compounds
No single study is appropriate as the basis for a
lifetime tolerable intake for barium. The US EPA (1998)
developed a reference dose (RfD) of 0.07 mg/kg body
weight per day with a uncertainty factor of 3 applied to a
NOAEL of 0.21 mg/kg body weight per day for barium
based on a weight-of-evidence approach that focuses on
four co-principal studies: the Wones et al. (1990)
experimental study in humans, the Brenniman & Levy
(1984) epidemiological study, and the medium- and long-
term exposure rat studies that employed adequate diets
and investigated both cardiovascular and renal end-
points (NTP, 1994). The McCauley et al. (1985) study of
unilaterally nephrectomized rats was used to support the
identification of the kidney as a co-critical target. In
addition, the approach includes a consideration of
supporting information from single-exposure and
mechanistic studies as well as from medium-term and
long-term exposure studies of animals on low-mineral
diets.
The identification of hypertension as a health end-
point of concern is supported by findings of hyperten-
sive effects in humans who ingested acutely high doses
of barium compounds, in workers who inhaled dusts of
barium ores and barium carbonate, in experimental
animals given barium intravenously, and in rats exposed
to barium in drinking-water while on restricted diets.
Based on these findings, lower-dose human studies were
conducted to examine the potential effects on blood
pressure in humans and on both blood pressure and
kidney function in animals. Although the experimental
study by Wones et al. (1990), together with the epide-
miological study by Brenniman & Levy (1984), did not
report any significant effects on blood pressure, they
establish a NOAEL in humans of 0.21 mg barium/kg
body weight per day. The animal data suggest that the
kidney may also be a sensitive target for ingested barium
from low-level exposure (Schroeder & Mitchener, 1975a;
NTP, 1984; McCauley et al., 1985); although the human
studies investigated hypertensive effects, the clinical
surveillance data did not uncover any renal dysfunction
or any other health abnormalities. Therefore, 0.21 mg
barium/kg body weight per day is used as the basis to
derive the tolerable intake for barium. The use of a
NOAEL from human studies increases the confidence in
the derivation of the tolerable intake value, which is
defined as an estimate (with uncertainty spanning
perhaps an order of magnitude) of a daily exposure of
the human population (including sensitive subgroups)
that is likely to be without an appreciable risk of
deleterious effects during a lifetime.
Therefore, the tolerable intake can be calculated as
the NOAEL of 0.21 mg/kg body weight per day divided
by an uncertainty factor of 10 to account for some data-
base deficiencies and potential differences between
adults and children, giving a tolerable intake of
0.02 mg/kg body weight per day.
Regarding inhalation exposure, the human
(Pendergrass & Greening, 1953; Doig, 1976; Seaton et al.,
1986) and animal inhalation (Muller, 1973; Tarasenko et
al., 1977) and intratracheal (Tarasenko et al., 1977;
Uchiyama et al., 1995) studies suggest that the
respiratory system is a target of barium toxicity. The data
also suggest that systemic effects, such as hyper-
tension, may occur following inhalation exposure
(Tarasenko et al., 1977; NIOSH, 1982; Zschiesche et al.,
1992). The human studies cannot be used to derive a
reference concentration (RfC) for barium because
exposure concentrations were not reported. Although
the NIOSH (1982) study measured barium breathing-zone
levels for some groups of workers, the barium exposure
levels were not measured in the group of workers with
the increased incidence of hypertension. The deficient
reporting of the methods and results of the only animal
medium-term/long-term inhalation exposure studies
(Muller, 1973; Tarasenko et al., 1977) precludes deriving
an RfC for barium from the animal data.
Under EPA’s Guidelines for Carcinogen Risk
Assessment (US EPA, 1986), barium would be classified
as Group D, not classifiable as to human carcinogenicity.
Although adequate long-term oral exposure studies in
rats and mice have not demonstrated carcinogenic
effects, the lack of adequate inhalation studies precludes
an assessment of the carcinogenic potential of inhaled
barium. Under the Proposed Guidelines for Carcinogen
Risk Assessment (US EPA, 1996, 1999), barium is consid-
ered not likely to be carcinogenic to humans following
oral exposure, and its carcinogenic potential cannot be
determined following inhalation exposure. Thus,
derivation of slope factors and unit risk values is
precluded.
Barium compounds exhibit close relationships with
calcium and strontium, which are also alkaline earth
metals. Owing to its similarity to calcium in its chemical
properties and because it lies below calcium in the
periodic table, barium is thought to interact with calcium
through biochemical pathways involving calcium
binding protein and compete for binding sites (IPCS,
1990). Hypertensive effects of barium in rats (Perry et al.,
1989) may have been due to inadequate calcium levels in
the diet.