Toxicological Review of Barium and Compounds

The subchronic rat studies included neurobehavioral and cardiovascular assessments. 

Behavioral assessments were conducted prior to exposure and at treatment days 45 and 90. 

Behavioral endpoints included spontaneous motor activity, forelimb and hindlimb grip strength, 

thermal sensitivity, and startle response to acoustic and air-puff stimulus.  The cardiovascular 

assessments were also conducted prior to exposure and at days 45 and 91.  Cardiac endpoints 

included EKG readings and blood pressure measurements.  

Three males and one female in the 4000 ppm treatment group died during the last week 

of the study.  These mortalities were considered by the authors to be chemical-related but the 

cause of death was not evident by histopathologic examination.  No other mortalities were 

observed.  Water consumption in the 4000 ppm treatment group was decreased by 30% relative 

to that of controls.  Body weights of animals in this treatment group were significantly reduced 

by approximately 13% for males and 8% for females when compared to controls. 

Increased absolute and relative kidney weights were observed in female rats from the 

2000 and 4000 ppm treatment groups when compared to controls; mean relative kidney weights 

were increased by 13% and 19%, respectively.  Mean relative kidney weight for male rats in the 

4000 ppm treatment group was increased by 12%.  Mean absolute liver weight was decreased 

16% in males from the 4000 ppm treatment group.  Mean absolute and relative liver weights in 

the females from the 4000 ppm treatment group were decreased 16% and 7%, respectively. 

Mean absolute thymus weight for females in the 4000 ppm treatment group was depressed 22%. 

The investigators attributed the changes in tissue weights of organs other than the kidney to be 

associated with the decrease in mean body weights. 

Chemical-related nephropathy were observed in 3/10 male and 3/10 female rats in the 

4000 ppm treatment group.  These lesions were described as minimal to mild, focal to multifocal 

areas of dilatation of the proximal convoluted tubules.  These changes were characterized as 

unlike the spontaneous renal lesions that occur in rats.  Tubule dilation was not observed in 

controls or in other treatment groups.  Early lesions of spontaneous nephropathy were observed 

in all males and a small number of females in all of the exposure groups as well as the controls 

(these changes were not characterized in the report).  Lymphoid depletion in the spleen and 

thymus was observed in animals from the 4000 ppm treatment group that died during the study. 

No other histologic changes were reported. 

Serum phosphorus levels were significantly elevated in female rats with drinking water 

concentrations 

$

500 ppm and in male rats receiving concentrations 

$

2000 ppm.  Dietz et al. 

(1992) did not consider the elevated serum phosphorus levels in female rats to be biologically 

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significant.  The investigators felt that the statistical significance of this observation was a result 

of  a mean value for the control group that was lower than historical controls.  No other 

chemical-related or biologically significant changes in serum or hematology parameters were 

observed. 

A significant decrease in the magnitude of undifferentiated motor activity was observed 

at day 90 in the 4000 ppm treatment group.  Marginal decreases were seen in all other barium-

exposed groups except the females in the 1000 ppm treatment group.  No significant or dose-

related changes were observed in other neurobehavioral endpoints.  The preliminary report of 

this study (Dietz et al., 1992) stated that there were no consistent effects on behavior produced 

by barium chloride and that the observed neurobehavioral changes could be attributed to the 

general condition of the rats and mice in the high dose groups.  The final NTP (1994) report did 

not discuss the toxicological significance of the neurobehavioral test results in rats. 

Cardiovascular assessments revealed no barium-associated differences in heart rate, EKG 

readings, or blood pressures.  A LOAEL of 180 mg/kg-day can be identified for a statistically 

significant decrease in body weights.  A NOAEL of 110 mg/kg-day can be identified for the 

absence of this effect. 

4.2.1.4.  NTP (1994) Chronic Rat Study 

In the chronic rat study, male and female F-344/N rats (60 animals/group/sex) received 

drinking water containing 0, 500, 1250, or 2500 ppm BaCl

2

×2H

2

O for 104 weeks (males) or 105 

weeks (females).  Using weekly water consumption and body weight data, the authors estimated 

the doses of barium were 15, 30, and 60 mg/kg-day for males and 15, 45, and 75 mg/kg-day for 

females, respectively.  The animals were fed an NIH-07 mash diet.  Barium concentration of the 

diet was not reported.  In a 15-month interim evaluation, venous blood was collected from all 

rats for hematology and clinical chemistry, which included analysis of plasma barium 

concentrations.  In addition, a limited number of rats (10 from each group) were sacrificed at 

month 15.  The remaining animals stayed on the study until they were moribund, died naturally, 

or were terminally sacrificed.  Necropsy and complete histopathologic examinations were 

performed on all animals.  Bone density and femur concentrations of barium, calcium, and 

phosphorus levels were measured at the 15-month interim.  Body weights were monitored 

throughout the study, and organ weights were determined in the animals sacrificed at the 15­

month interim. 

The survival of the exposed males was increased (62%, 58%, and 67% for the 500, 1250, 

and 2500 ppm treatment groups, respectively) compared to the control group (44%).  The 

increased survival of the treated animals was attributed to a high incidence of leukemia in the 

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