Toxicological Review of Barium and Compounds

controls.  The authors did not present any explanation for why the exposed animals may have 

been more resistant than the controls.  Survival of the females was not significantly affected. 

The final mean body weights for male rats in the 2500 ppm treatment group were 5% lower than 

in the control group.  The final mean body weights of females in the 1250 and 2500 ppm 

treatment groups were 6% and 11% lower, respectively, than in controls.  Water consumption 

decreased with increasing concentrations of barium chloride.  In the 2500 ppm treatment group, 

water consumption was decreased 22% in males and 25% in females relative to controls. 

Barium serum concentrations were significantly elevated in males from all three treatment 

groups and in females from the two highest dose groups.  Barium serum concentrations increased 

in a dose-dependent manner with a 71% and 93% increase observed in high dose group males 

and females, respectively.  Barium concentrations in upper, middle, and lower sections of femurs 

from animals in the high dose group were approximately three orders of magnitude higher than 

the control group animals.  Calcium concentrations in the upper section of the femur were 

decreased 6% and 5% in high dose group males and females, respectively.  No effect of barium 

treatment was observed on bone density. 

Mean relative kidney weights were increased for females from the 1250 and 2500 ppm 

treatment groups by 6% and 15%, and absolute kidney weights were increased by 3% and 4%, 

respectively.  Mean absolute kidney weights in males from these two exposure groups were 

decreased by 7% and 9%, respectively, while relative kidney weights were essentially 

unchanged.  Mean absolute liver weights were decreased in females from all exposure groups 

(6% -13%).  Relative brain and uterine or testicular weights were increased in animals receiving 

2500 ppm.  Absolute heart weights were decreased in females from the 1250 and 2500 ppm 

treatment groups. 

Nephropathy was observed in the majority of animals from all groups, including the 

controls.  These lesions were not considered to be chemical-related.  No other histologic changes 

were reported. 

No increases in the incidence of neoplasms were observed in the barium-treated rats. 

Significant negative trends were observed in the incidence of mononuclear cell leukemia in male 

rats (35/50, 25/50, 26/50, and 15/50 in 0, 500, 1250, and 2500 ppm groups, respectively), benign 

and malignant adrenal medulla pheochromocytoma in male rats (13/49, 11/50, 12/49, and 6/50, 

respectively), and mammary gland neoplasia (fibroadenoma, adenoma, or carcinoma) in female 

rats (17/50, 21/50, 13/50, and 11/50, respectively).  A LOAEL of 60 mg/kg-day can be identified 

for a statistically significant decrease in body weights.  A NOAEL of 30 mg/kg-day can be 

identified for the absence of this effect. 

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4.2.1.5.  McCauley et al. (1985) 

McCauley et al. (1985) administered barium in drinking water to rats for various 

durations.  The animals were provided free access to either Purina rat chow containing 15 mg/kg 

Ba or Tekland rat chow with less than 1 mg/kg Ba.  The various studies examined the effects of 

barium exposure on histology, EKG readings, and blood pressure.  The blood pressure studies 

included electron microscopic evaluations of the kidneys.  The following exposure regimes were 

used in the histology studies: (1) male CD Sprague-Dawley rats (12/group) were exposed to 0, 1, 

10, 100, or 250 ppm barium (as barium chloride) in drinking water for 36 weeks, (2) female CD 

Sprague-Dawley rats (12/group) were exposed to 0 or 250 ppm barium in drinking water for 46 

weeks, and (3) male CD Sprague-Dawley rats (10/group) were exposed to 0, 1, 10, or 100 ppm 

barium in drinking water for 68 weeks.  The authors reported that no significant differences in 

food or water intake or body weight were observed, but they did not report the actual data.  Rats 

receiving 10 ppm barium in their drinking water ingested 1.5 mg/kg-day from water and 1 

mg/kg-day from the Purina diet.  The measured barium intake for this group was used to estimate 

total barium intake for the 0, 1, 10, 100, and 250 ppm exposure groups as 1, 1.15, 2.5, 16, and 

38.5 mg/kg-day.  

Histologic evaluations of the gastrointestinal tract, liver, heart, adrenal gland, brain, 

respiratory tract, spleen, thymus, kidneys, ovaries, and testes did not reveal any barium-related 

lesions.  Retinal lesions were observed in 5/12 males exposed to 100 ppm for 36 weeks and 7/12 

females exposed to 250 ppm for 46 weeks, but were not seen in other treatment groups.  Retinal 

dystrophy is a common pathology in CD Sprague-Dawley rats (Schardein et al., 1975).  No 

increase in the incidence of neoplasms was observed in the barium-exposed rats, but this finding 

was considered inconclusive because the study duration was less than lifetime.

 In the EKG study, CD Sprague-Dawley rats (10-11/group, sex not specified) were given 

drinking water containing 0 or 250 ppm barium (as barium chloride) for 5 months and Purina rat 

chow (estimated intakes of 1 and 38.5 mg/kg-day, respectively, based on the estimates from the 

histology study).  EKG readings were obtained at 0, 4, and 60 minutes after an intravenous 

injection of 0.5 

:

g/kg of L-norepinephrine (NE).  Barium exposure led to a significant 

enhancement of NE-induced bradycardia compared with controls 4 minutes after NE 

administration.  At 60 minutes, the heart rates of controls were still depressed, whereas those of 

the barium-exposed animals were approaching normal.  No significant alterations in the PR, QS, 

QT, and ST interval durations or peak amplitudes were observed in electrocardiograms. 

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