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BARIUM IN DRINKING-WATER - Who/sde/wsh/03. 04/76

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In an associated subchronic study, groups of 10 male and 10 female F344/N rats 

received drinking-water containing 0, 125, 500, 1000, 2000 or 4000 mg of barium 

chloride dihydrate per litre for 13 weeks, corresponding to 0, 10, 30, 65, 110 and 200 

mg of barium per kg of body weight per day in males and 0, 10, 35, 65, 115 and 180 

mg of barium per kg of body weight per day in females. Although water consumption 

and body weight were reduced in the top dose groups, there were no clearly chemical-

related differences in any parameters except for renal tubular dilatation at the top dose 

and elevated serum phosphorus levels at 2000 and 4000 mg/litre. A NOAEL of 1000 

mg/litre (equivalent to 65 mg of barium per kg of body weight per day) was identified 

in this study (US NTP, 1994). 


5.3 Long-term exposure 


In a study on the lifetime exposure of Long-Evans rats to 5 mg of barium per litre as 

barium acetate in drinking-water, the only significant effect reported was an increase 

in proteinuria in males (Schroeder & Mitchener, 1975a). In a similar study in which 5 

mg of barium per litre as barium acetate was administered in drinking-water to 

Charles River CD mice over their entire life span, there was a slight reduction in the 

survival of males, but no effects on body weight gain, oedema or blanching of incisor 

teeth (Schroeder & Mitchener, 1975b). No histopathological effects were found in 34 

tissues of male and female Sprague-Dawley rats exposed to 1, 10, 100 or 250 mg of 

barium per litre as barium chloride in drinking-water for up to 68 weeks (McCauley et 

al., 1985). 


Groups of female Long-Evans rats were exposed to 1, 10 or 100 mg of barium per 

litre as barium chloride in drinking-water for 1, 4 or 16 months (Perry et al., 1983), 

equivalent to average doses of 0.051, 0.51 and 5.1 mg of barium per kg of body 

weight per day (US EPA, 1985b). Mean systolic pressure remained unchanged in 

animals exposed to the lowest dose for 16 months. At the intermediate dose, there 

were mean increases in blood pressure of 0.533–0.933 kPa (4–7 mmHg) by 8 months, 

which persisted thereafter. In rats receiving the highest dose, significant and persistent 

increases in mean systolic pressure of 1.60 kPa (12 mmHg) were seen after only 1 

month, gradually increasing to a mean of 2.13 kPa (16 mmHg) after 16 months of 

exposure. Rates of cardiac contraction, electrical excitability and high-energy 

phosphate and phosphorylation potential were decreased. As increases in systolic 

pressure of 0.533–0.933 kPa (4–7 mmHg) are deemed small enough not to constitute 

an adverse effect, the NOAEL can be considered to be 0.51 mg of barium per kg of 

body weight per day, and the LOAEL is 5.1 mg of barium per kg of body weight per 



A chronic study (US NTP, 1994) was carried out in which groups of 60 male and 60 

female B6C3F1 mice received barium chloride dihydrate in drinking-water at 

concentrations of 0, 500, 1250 or 2500 mg/litre for 103 weeks (males) and 104 weeks 

(females). The average daily doses for the treated groups using measured water 

consumption and body weights corresponded to 30, 75 and 160 mg of barium per kg 

of body weight for males and 40, 90 and 200 mg of barium per kg of body weight for 






At the 15-month interim evaluation, venous blood was collected from all mice for 

haematology and clinical chemistry examination. In addition, a limited number of 

mice from each of the four dose groups were sacrificed at 15 months. The remaining 

animals continued on the study until they were moribund, died naturally or were 

sacrificed at the end of the study. Necropsy and complete histopathological 

examinations were performed on all animals. At the 15-month interim evaluation, the 

absolute and relative spleen weights of the female mice that received 2500 mg/litre 

were significantly lower than those of the controls, and the absolute and relative 

thymus weights of the male mice that received 2500 mg/litre were marginally lower 

than those of the controls. Determination of haematology and clinical chemistry 

parameters (e.g., phosphorus, calcium and urea nitrogen) at the 15-month interim 

evaluation showed no significant differences between control and exposed mice. At 

2500 mg/litre, survival rates for mice at the end of the study (65% for males and 26% 

for females) were significantly lower than those of the controls (89% for males and 

76% for females). Survival was not significantly lower relative to controls at the 

lower dose levels. In high-dose male and female mice, the final mean body weights 

were 8% and 12% lower, respectively, than those of the corresponding control groups. 

Water consumption was not affected by the treatment. 


The incidence of nephropathy at the end of the study was significantly increased in 

mice receiving 2500 mg/litre. The nephropathy at the highest dose was chemical 

related and morphologically distinct from the spontaneous degenerative lesions 

commonly observed in aging B6C3F1 mice. Lymphoid depletions in the spleen, 

thymus and lymph nodes were observed in high-dose male and female mice, 

particularly in animals that died early, and were thought to be the result of debilitation 

associated with nephropathy. There were no other chemical-related histological 

changes. Thus, it was considered that 1250 mg/litre (75 mg of barium per kg of body 

weight per day in males and 90 mg of barium per kg of body weight per day in 

females) was the NOAEL in this study. 


The incidences of neoplasms in the barium-exposed mice were not significantly 

higher than in control mice. In the 2500 mg/litre female mice, the incidences of 

several neoplasms were significantly lower than in the controls; the authors attributed 

this finding to the marked reduction in survival in the barium-exposed animals. 


In the same chronic study (US NTP, 1994), groups of 60 male and 60 female F344/N 

rats received drinking-water containing 0, 500, 1250 or 2500 mg of barium chloride 

dihydrate per litre for 104 weeks (males) or 105 weeks (females). The authors 

estimated daily doses for the treated groups using measured water consumption and 

body weights as 15, 30 and 60 mg of barium per kg of body weight for males and 15, 

45 and 75 mg of barium per kg of body weight for females. As in the study on mice, a 

15-month interim evaluation was performed with venous blood being collected from 

all rats for haematology and clinical chemistry examination. In addition, a limited 

number of rats were sacrificed. The remaining animals stayed on the study until they 

were moribund, died naturally or were terminally sacrificed. Necropsy and complete 

histopathological examinations were performed on all animals. Body weights were 

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