Toxicological Review of Barium and Compounds

cancer in situ.  Sixteen days after topical application, the cell transformations were not observed 

in the deeper layers of the epithelium but were still present in superficial and intermediate areas. 

4.4.4.  Genotoxicity 

There is a limited amount of information available on the genotoxicity of barium 

compounds.  No in vivo studies have been conducted.  Most in vitro studies found that barium 

chloride and barium nitrate did not induce gene mutations in bacterial assays with or without 

metabolic activation.  Ames assays with Salmonella typhimurium strains TA1535, TA1538, 

TA1537, TA97, TA98, and TA100 with or without metabolic activation (Monaco et al., 1990, 

1991; NTP, 1994), rec assays with Bacillus subtilis strains H17 and H45 (Nishioka, 1975; 

Kanematsu et al., 1980), and a microscreen assay with Escherichia coli (Rossman et al., 1991) 

with metabolic activation have produced negative results with barium chloride.  Negative results 

have also been observed for barium nitrate in the rec assay using B. subtilis strains H17 and H45 

(Kanematsu et al., 1980).  Barium chloride induced gene mutations in L5178Y mouse lymphoma 

cells with metabolic activation but not in the absence of metabolic activation (NTP, 1994). 

Neither barium acetate nor barium chloride decreased the fidelity of DNA synthesis in avian 

myeloblastosis virus DNA polymerase (Sirover and Loeb, 1976).  In mammalian cells, barium 

chloride did not induce sister chromatid exchanges or chromosomal aberrations in cultured 

Chinese hamster ovary cells, with or without activation (NTP, 1994). 

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4.5.  SYNTHESIS AND EVALUATION OF MAJOR NONCANCER EFFECTS AND 

MODE OF ACTION—ORAL AND INHALATION 

4.5.1.  Oral Exposure 

Highly soluble barium compounds are more toxic than insoluble compounds like barium 

sulfate.  Accidental or intentional ingestion of soluble barium salts (e.g., barium carbonate, 

barium chloride) produces hypokalemia and acute hypertension (Koch, 2003; Downs et al., 

1995).  Systemic effects of acute barium toxicity include vomiting, diarrhea, cardiac arrhythmia, 

muscular paralysis, and death (CDC, 2003; Jacobs et al., 2002; Deng et al., 1991; Schorn et al., 

1991; Roza and Berman, 1971).  The acute pathophysiological effects of barium are linked with 

two modes of action: direct muscular stimulation (skeletal, cardiac, and smooth), and 

hypokalemia (Koch, 2003; Downs et al., 1995).  The latter effect is associated with the ability of 

the barium ion to block potassium (K

+

) channels and interfere with passive K

+

 diffusion (Walter 

et al., 2001; Downs et al., 1995). 

Several studies have investigated the effects of long-term barium exposure on the human 

cardiovascular system.  Brenniman et al. (1979) reported higher age-adjusted mortality rates for 

cardiovascular diseases among individuals 65 years and older living in Illinois communities with 

mean drinking water concentrations of 2-10 mg/L barium when compared to communities with 

mean drinking water concentrations of 0.2 mg/L or less.  However, the investigators questioned 

the significance of these data because they did not control for several important variables 

including length of residence in the study communities and the use of water softeners that may 

have reduced barium or increased sodium concentrations.  This study did not account for some 

important risk factors for hypertension such as smoking, diet, and exercise.  Another limitation 

to this study was the use of community-wide exposure estimates.  Because these investigators 

did not have individual consumption data they were unable to link individual exposures with 

specific outcomes. 

Brenniman et al. (1981) conducted a morbidity study of two Illinois communities with a 

70-fold difference in barium drinking water concentrations.  No differences in mean systolic or 

diastolic blood pressures were observed.  A NOAEL of 0.21 mg/kg-day was identified by EPA 

using a standard estimate of drinking water intake (2 L/day) and an average body weight (70 kg).

 There were several limitations to the design of this study: a relatively small number of subjects 

was examined (n=85 in the matched subpopulation that was controlled for key risk factors); 

blood pressure was measured repeatedly during a 20-minute period; community-wide exposure 

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estimates were used; and a number of important risk factors for hypertension were not controlled 

for, including diet and exercise. 

Wones et al. (1990) conducted a before-after comparison of 11 subjects who were 

exposed to two concentrations of barium (5 and 10 ppm) over a period of 10 weeks.  The first 

two weeks served to establish a baseline, and then progressively greater concentrations of barium 

were administered for a period of four weeks each.  No difference in mean systolic or diastolic 

blood pressures was observed.  A NOAEL of 0.21 mg/kg-day was identified for this study by 

EPA using standard estimates for drinking water intake (2 L/day) and average body weight (70 

kg).  Coincidently, this NOAEL is identical to the one identified for the Brenniman et al. (1981) 

morbidity study.  This study was limited by a very small number of participants and short 

exposure durations (4 weeks for each exposure level). 

Acute exposure to large doses of barium is known to produce hypertension in humans 

(CDC, 2003; Downs et al., 1995).  However, neither Wones et al. (1990), nor Brenniman and 

Levy (1984), nor Brenniman et al. (1981) obtained sufficient dose-response data to establish an 

association between repeated human exposure to barium in drinking water and hypertension. 

Conversely, these studies did not discount the possibility that chronic barium in drinking water 

can produce hypertension.  Moreover, since both studies only examined the effect of barium on 

hypertension, it is not known if those exposure levels were associated with other adverse effects, 

such as renal damage. 

Animal studies also provide both positive and negative evidence of an association 

between barium exposure and hypertension.  Intravenous infusion of barium chloride in 

anesthetized dogs or guinea pigs resulted in increased blood pressure and cardiac arrhythmias 

(Hicks et al., 1986; Roza and Berman, 1971).  Perry et al. (1989, 1985) reported hypertension in 

Long-Evans rats exposed for 16 months to 100 ppm barium in drinking water (estimated to be 6 

mg/kg-day).  Conversely, NTP (1994) evaluated blood pressure and EKG readings of rats 

exposed for 13 weeks to 500, 1250, or 2500 ppm barium chloride in drinking water.  Barium 

doses were estimated to be 15, 30, 60 mg/kg-day and 15, 45, and 75 mg/kg-day for males and 

females, respectively.  No association was detected between subchronic barium exposure and 

cardiovascular toxicity in rats at the highest level tested (200 mg/kg-day).  Likewise, McCauley 

et al. (1985) did not observe hypertension in Sprague-Dawley rats exposed to barium in drinking 

water (up to 150 mg/kg-day) for 16 weeks.  However, this study did not include untreated 

controls. 

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