Toxicological Review of Barium and Compounds

In the blood pressure study, 26 groups of animals (6/group, sex not specified) were fed 

Tekland rat chow and administered barium in their drinking water for 16 weeks.  Five groups of 

CD Sprague-Dawley rats received 0, 3, 10, or 100 ppm barium in their drinking water.  The same 

concentrations of barium were administered to five groups of CD Sprague-Dawley rats in 0.9% 

NaCl.  Eight additional groups of unilaterally nephrectomized CD Sprague-Dawley rats received 

1, 10, 100, or 1000 ppm barium in either water or 0.9% NaCl.  These same concentrations of 

barium were provided in 0.9% NaCl to two specially bred strains of rats: Dahl salt-sensitive and 

Dahl salt-resistant.  These inbred strains are derived from Sprague-Dawley rats and used to study 

salt-dependent hypertension.  Estimated doses corresponding to 0, 1, 3, 10, 30, 100, and 1000 

ppm exposures were 0, 0.15, 0.45, 1.5, 4.5, 15, and 150 mg/kg-day, respectively.  

The salt-sensitive Dahl rats had transiently elevated blood pressure (approximately 150­

160 mm Hg) during the first 1-2 weeks of exposure to 1 or 10 ppm barium.  The investigators 

considered this to be an effect of the NaCl solution on the salt-sensitive animals.  No evidence of 

hypertension was observed in Dahl salt-resistant rats that received the same treatments.  Some 

fluctuations of blood pressure were observed in other treatment groups, but none were 

considered to be indicative of hypertension. Thus, there was no indication that barium 

contributed to hypertension in this animal model, but further interpretation of the results is 

problematic because of the lack of control groups. 

Electron microscopy examination of the kidneys  was conducted for all rats in the blood 

pressure studies.  Structural changes were observed in the glomeruli of rats that received 1000 

ppm BaCl

2

×2H

2

O, including fused podocyte processes, thickening of the capillary basement 

membrane, and myelin figures in Bowman’s space.  No histopathologic changes were observed 

in the arteriolar vessel walls or in the tubules of the nephrons. 

The only groups that received 1000 ppm barium were the unilaterally nephrectomized 

rats and the Dahl salt-sensitive and salt-resistant rats that received barium in 0.9% NaCl. 

Normal CD Sprague-Dawley rats were not tested at this exposure level.  No glomerular effects 

were seen at the next lower exposure level, 100 ppm, or in any other treatment group. 

4.2.1.6.  Tardiff et al. (1980) 

Tardiff et al. (1980) exposed male and female Charles River rats (30 animals/dose /sex) 

continuously to 0, 10, 50, or 250 ppm barium (as barium chloride) in drinking water for 4, 8, or 

13 weeks.  The authors estimated doses for the treated groups as 1.7, 8.1, and 38.1 mg Ba/kg-day 

24

---

for males and 2.1, 9.7, and 45.7 mg Ba/kg-day for females.  Rats were fed Tekland mouse/rat 

diet pellets, which contributed a baseline dose of 0.5 

:

g Ba/kg-day.  No deaths occurred and 

there were no clinical signs of toxicity.  Food consumption and body weights in the treated 

groups were essentially the same as in the control groups.  Water consumption, however, was 

depressed in both sexes at 250 ppm barium.  Slight decreases in relative adrenal weights 

occurred in males at 

$

50 ppm at 8 weeks and in females at all barium concentrations at 13 

weeks, but these changes were not dose related, and a slight increase occurred in females at 250 

ppm at 8 weeks.  No treatment-related changes were seen in hematologic parameters, serum 

alkaline phosphatase,  serum glutamate oxalate transaminase,  serum glutamate pyruvate 

transaminase, BUN, serum ions (sodium, potassium, calcium), gross pathology, and 

histopathology of the liver, kidneys, spleen, heart, brain, muscle, femur, and adrenal glands. 

Blood pressure and endpoints sensitive for glomerular damage (electron microscopic 

examination or urinary excretion of protein) were not investigated.  This study identifies a 

subchronic NOAEL of 250 ppm (38.1-45.7 mg Ba/kg-day). 

4.2.1.7.  Perry et al. (1989, 1985) 

Perry et al. (1989, 1985) exposed female weanling Long-Evans rats to 0, 1, 10, or 100 

ppm barium (as barium chloride) in drinking water for 1, 4, and 16 months (13 treated rats per 

duration and 21 control rats per duration).  Drinking water was fortified with five essential 

metals (1 ppm molybdenum, 1 ppm cobalt, 5 ppm copper, 10 ppm manganese, and 50 ppm zinc). 

All animals received a rye-based diet with low trace metal content.  The diet contained 1.5 ppm 

barium and 3,800 ppm calcium.  Based on a time-weighted average (TWA) water intake (20 

mL/day) and body weight (0.334 kg) estimated from reported values for the 16-month period, 

barium doses from drinking water can be estimated at 0, 0.06, 0.6, and 6 mg Ba/kg-day.  The diet 

contained 1.5 ppm barium.  Based on the TWA body weight and a TWA food intake of 20 g/day 

estimated from reported values for the 16-month period, the barium dose from the diet can be 

estimated at 0.1 mg Ba/kg-day.  Combining the doses from water and diet results in estimated 

intakes of 0.1, 0.15, 0.7, and 6 mg Ba/kg-day.  The cumulative intake from drinking water and 

diet was reported by the authors as 16, 28, 134, and 1198 mg Ba/rat for the 0, 1, 10, and 100 ppm 

groups at 16 month (termination).  Dividing the total doses by the TWA body weight and by 487 

days (16 month) gives estimated doses from water plus diet of 0.1, 0.2, 0.8, and 7 mg Ba/kg-day. 

These values are similar to those estimated above from the water and diet concentrations of 

barium.  All the above estimates are approximate because the authors reported intake and body 

weight values only for controls, stating that the values for the dosed groups were no different. 

Accordingly, the TWA body weight and water and food intake values above were based on the 

control data and were used for all exposure groups. 

25

---