Toxicological Review of Barium and Compounds

al., 1977).  Similar results were observed in rats exposed to 5.2 mg/m

3

 barium carbonate (3.6 mg 

Ba/m

3

) 4 hours day, 6 days/week for 4 months. 

Tarasenko et al. (1977) also reported that a shortening of the mean duration of the estrous 

cycle and an alteration in the proportion of mature and dying ovarian follicles were observed in 

female rats exposed to 13.4 mg/m

3

 barium carbonate (9.3 mg Ba/m

3

) for 4 months (duration of 

daily exposure or frequency of exposure were not reported), as compared with a control group. 

These effects were not observed in females exposed to 3.1 mg/m

3

 (2.2 mg Ba/m

3

).  The authors 

also noted that dams in the 13.4 mg/m

3

 group gave birth to underdeveloped offspring that 

showed considerable mortality and slow increases in body weight during the first 2 months of 

life.  The authors did not state whether the barium carbonate-exposed females were mated to 

exposed or unexposed males. 

4.4.  OTHER STUDIES 

4.4.1.  Acute Toxicity Data 

Intentional or accidental human ingestion of soluble barium compounds causes 

gastroenteritis, hypokalemia, acute hypertension, cardiac arrhythmias, skeletal muscle paralysis, 

and death (CDC, 2003; Jourdan et al., 2001; Downs et al., 1995; Tenenbein, 1985).  Intravenous 

infusion of barium chloride into anesthetized dogs or guinea pigs resulted in increased blood 

pressure and cardiac arrhythmias (Hicks et al., 1986; Roza and Berman, 1971).  In the dog study, 

mean blood pressure readings increased from 138/86 to 204/103 in animals (n=24) receiving 1.0 

:

mol/kg/min.  A higher infusion rate, 4.0 

:

mol/kg/min, produced mortality in a few minutes as a 

result of respiratory paralysis and ventricular tachycardia.  The study in dogs also reported 

skeletal muscle flaccidity and paralysis (Roza and Berman, 1971).  Determination of plasma 

potassium concentrations revealed severe hypokalemia, which appeared to result from an 

extracellular-to-intracellular shift of potassium.  Barium serum concentrations were not 

measured.  The hypertension did not appear to be mediated through the renin-angiotensin system 

because it was not prevented by bilateral nephrectomy of the dogs.  Likewise, the hypertensive 

effect did not appear to be caused by adrenal medullary stimulation since the coadministration of 

the adrenergic receptor antagonist phentolamine did not mitigate the effect.  Simultaneous 

infusion of potassium into the dogs abolished the cardiac effects and the skeletal muscle 

flaccidity but did not affect hypertension. 

4.4.2.  Intratracheal Administration 

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In a study conducted by Tarasenko et al. (1977), albino rats and rabbits (number of 

animals was not specified) were administered an intratracheal dose of 50 mg barium carbonate 

(35 mg barium).  Three months after administration, sclerotic changes were observed in the 

lungs.  The severity of the sclerosis progressed.  At 9 months, fibrous pneumonia with necrosis 

of mucous membrane of the large bronchi was also observed. 

Uchiyama et al. (1995) administered a single intratracheal dose of 0.015, 0.3, or 0.6 

mL/kg of BA147 (a preparation containing 85% barium sulfate) to rabbits.  No treatment-related 

effects on pulmonary ventilation (measured 1 day, 3 days, and 1, 2, and 4 weeks after dosing), 

levels of blood gases (measured at the same time as pulmonary ventilation), or lung weights 

were observed.  Soft X-rays of the lungs revealed dose-related shadows.  Bronchopneumonia, 

bronchitis, or bronchiolitis was observed in 28 of 36 animals during the first week after dosing. 

Thereafter, the alterations were not observed.  No further details of this study were available 

from the English abstract of the article in Japanese. 

4.4.3.  Carcinogenicity Studies—Topical Administration 

In a study to determine the safety of components of intrauterine contraceptive devices, a 

single topical application of 1.25 mM barium chloride was applied to the squamocolumnar 

junctional area of the cervix of a woman with no known history of abnormal cervical cytology 

results (Ayre and LeGuerrier, 1967; Ayre, 1966).  A cervical cell scraping was performed 48 

hours after barium chloride application.  The topical application of barium chloride and cervical 

cell scraping were repeated four times at intervals of 4-6 weeks.  A number of cell 

transformations resembling severe premalignant dysplasia were observed; the transformed cells 

were described as bizarre, multinucleated cells with profoundly altered nuclear chromatin.  One 

to three weeks after barium chloride application, these cellular alterations were no longer 

observed. 

In another study (Ayre and LeGuerrier, 1967; Ayre, 1966), 1.25 mM barium chloride was 

mixed with equal amounts of 70% DMSO, and a single topical application of the mixture was 

applied to the squamocolumnar junctional area of the cervix.  It is assumed that only one subject 

was used, and it was not reported whether this was the same woman previously tested.  Cervical 

scrapings were performed after 48 hours, 72 hours, and twice weekly for an unspecified amount 

of time.  The cell transformations were similar to extreme dysplasia; in addition, spindle cells 

and cells with marked hyperchromatism with multiple chromatin bundles and enlarged irregular 

nucleated forms were observed.  Cell transformations were also observed in deeper layers of the 

squamous epithelium.  The authors noted that the transformed cells resembled cell findings of 

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