Barium and barium compounds
15
In a 16-week blood pressure study (McCauley et
al., 1985), normotensive rats were fed Tekland rat chow
(0.5 mg barium/kg body weight per day) and adminis-
tered barium in drinking-water or in 0.9% sodium chloride
solution as drinking-water (estimated daily barium doses
of 0, 0.45, 1.5, 4.5, or 15 mg/kg body weight). Unilaterally
nephrectomized rats were similarly treated (estimated
daily doses of 0.15, 1.5, 15, or 150 mg barium/kg body
weight), while groups of Dahl salt-sensitive and Dahl
salt-resistant rats received estimated daily doses of 0.15,
1.5, 15, or 150 mg barium/kg body weight in 0.9% sodium
chloride as drinking-water. The authors stated that all
groups showed fluctuations of blood pressure. No
indications of hypertension were observed, but there
were no 0 mg barium/litre / 0.9% sodium chloride
controls in the study. Electron microscopic examination
of kidneys in all the rats in the blood pressure studies
demonstrated no changes in arteriolar vessel walls or in
tubules of the nephrons. However, structural changes in
glomeruli were observed in the high-dose (150 mg
barium/kg body weight per day) nephrectomized, Dahl
salt-sensitive, and Dahl salt-resistant groups. No
glomerular effects were seen at the next lower exposure
level in any group of rats.
Data on the toxicity of barium compounds in
animals following inhalation exposure are limited to a
study in which male albino rats were exposed to barium
carbonate at 0, 1.15, or 5.20 mg/m
3
(0, 0.80, or 3.6 mg
barium/m
3
) for 4 h/day, 6 days/week, for 4 months
(Tarasenko et al., 1977). At 5.20 mg/m
3
(but not 1.15
mg/m
3
), reported alterations included a 21% decrease in
body weight gain, a 32% increase in arterial pressure,
altered haematological parameters, altered serum
chemistry parameters, increased calcium levels in the
urine, impaired liver function, and histological alterations
in the heart, liver, kidneys, and lungs. The authors noted
that the heart, liver, and kidneys “had a character of mild
protein (‘granular’) dystrophy.”
8.5
Long-term exposure and
carcinogenicity
NTP (1994) treated male and female F344/N rats (60
animals per dose group per sex) with deionized drinking-
water containing 0, 500, 1250, or 2500 mg barium chloride
dihydrate/litre for 2 years. Daily doses of barium were
estimated to be 0, 15, 30, or 60 mg/kg body weight for
males and 0, 15, 45, or 75 mg/kg body weight for females.
The animals were fed an NIH-07 mash diet; the barium
content of the diet was not reported. In this study,
neurobehavioural and cardiovascular tests were not
performed. Reported exposure-related effects included
reduced body weights in some mid- and high-dose rats,
dose-related decreased water consumption, and
significantly increased relative kidney weights in high-
dose females (the only indication of potential adverse
renal effects). Thus, the 2500 mg/litre exposure level (60
mg barium/kg body weight per day for males and 75 mg
barium/kg body weight per day for females) may be a
chronic NOAEL or LOAEL for rats, depending on
interpretation of the increased relative kidney weight in
females. When considered together with the results in
the 13-week NTP (1994) study in rats, in which increased
relative and absolute kidney weights were seen in female
rats receiving 2000 mg barium/litre in drinking-water (115
mg barium/kg body weight per day) and kidney lesions
accompanied by increases in relative and absolute
kidney weights were seen in female rats at 4000 mg/litre
(180 mg barium/kg body weight per day), the increased
relative kidney weight in females of the 2-year study is
suggestive of potential renal effects. Therefore, 75 mg
barium/kg body weight per day is designated a chronic
LOAEL and 45 mg barium/kg body weight per day a
chronic NOAEL for female rats for renal effects in the
NTP (1994) study. There were no significant increases in
incidences of neoplasms in the barium-exposed rats.
Significant negative trends were observed in the
incidences of mononuclear cell leukaemia in male rats,
benign and malignant adrenal pheochromocytoma in
male rats, and mammary gland neoplasms (fibroadenoma,
adenoma, or carcinoma) in female rats.
NTP (1994) also treated B6C3F
1
mice (60 animals
per dose group per sex) with drinking-water containing 0,
500, 1250, or 2500 mg barium chloride dihydrate/litre for 2
years. Estimated daily doses were 0, 30, 75, or 160 mg
barium/kg body weight for males and 0, 40, 90, or 200 mg
barium/kg body weight for females. The animals were fed
an NIH-07 mash diet; the barium content of the diet was
not reported. Neurobehavioural and cardiovascular tests
were not performed. At the 15-month interim evaluation,
the absolute and relative spleen weights of the 2500
mg/litre female mice were significantly (P
#
0.01) lower
than those of the controls, and the absolute and relative
thymus weights of the 2500 mg/litre male mice were
marginally lower than those of the controls.
Additionally, survival rates for the 2500 mg/litre mice at
the end of study were significantly (P
#
0.01) lower than
those of the controls, which was attributed to chemical-
related renal lesions. These renal lesions were
characterized by tubule dilatation, renal tubule atrophy,
tubule cell regeneration, hyaline cast formation,
multifocal interstitial fibrosis, and the presence of
crystals, primarily in the lumen of the renal tubules.
Lymphoid depletions in the spleen, thymus, and lymph
nodes were observed in 2500 mg/litre male and female
mice, particularly in animals that died early, and were
thought to be the result of debilitation associated with
nephropathy. Thus, the chronic LOAEL in mice is 2500