Concise International Chemical Assessment Document 33

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 

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