Toxicological Review of Barium and Compounds

4.5.2.  Inhalation Exposure 

Several human studies have investigated the toxicity of inhaled barium compounds. 

Exposure to insoluble forms of barium, such as barium sulfate and barite ore, results in baritosis 

(Seaton et al., 1986; Doig, 1976; Pendergrass and Greening, 1953).  Although profuse opacities 

were observed on the radiographs, no alterations in lung function, abnormal physical findings, or 

increases in the incidence of subjective symptoms were reported.  It appears that the 

accumulation of barium sulfate in the lungs will diminish upon termination of barium exposure. 

Barium exposure levels resulting in baritosis have not been reported.  NIOSH (1982) reported an 

increased incidence of hypertension in workers exposed to an unspecified concentration of 

barium.  Although the results of this study are consistent with the suggestion of hypertension 

following oral exposure to barium compounds, the results of the NIOSH (1982) study should be 

interpreted cautiously because it is likely that the workers were also exposed to other metals, 

including lead, which has a known hypertensive effect. 

Inhalation toxicity data in animals are limited to inhalation exposure and intratracheal 

administration studies by Tarasenko et al. (1977) and an intratracheal administration study by 

Uchiyama et al. (1995).  In the Tarasenko et al. (1977) inhalation study, a number of adverse 

effects was reported in rats exposed to 5.2 mg/m

3

 barium carbonate (3.6 mg/m

3

 barium) 

4 hours/day, 6 days/week for 4 months.  The effects included alterations in some hematological 

and serum chemistry parameters, perivascular and peribronchial sclerosis with collagenation in 

the lungs, and increases in arterial pressure.  It does not appear that statistical analysis of the data 

was performed, and incidence data for the lung effects were not reported.  No adverse effects 

were observed in the rats exposed to 1.15 mg/m

3

 barium carbonate (0.8 mg/m

3

 barium).  The 

finding of lung lesions following exposure to barium carbonate was confirmed by an 

intratracheal administration study conducted by Tarasenko et al. (1977).  In this study, fibrous 

pneumonia and necrosis of the mucous membrane of the large bronchi was observed 9 months 

after animals received an intratracheal dose of 50 mg barium carbonate (35 mg barium).  As with 

the inhalation study, the results of this study were poorly reported.  Uchiyama et al. (1995) also 

found pulmonary effects (bronchopneumonia, bronchitis, or bronchiolitis) in rabbits 

intratracheally administered a preparation containing 85% barium sulfate.  Although studies 

conducted by Tarasenko et al. (1977) suggest that inhalation exposure to barium carbonate may 

result in reproductive effects, confidence in these studies is very low due to poor reporting of 

study design and results.  Thus, the potential of barium to induce developmental and/or 

reproductive effects has not been adequately assessed following inhalation exposure. 

4.6.  WEIGHT-OF-EVIDENCE EVALUATION AND CANCER CHARACTERIZATION 

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In the only available human study, cell transformations were observed following a single 

topical application of barium chloride to the cervix (Ayre and LeGuerrier, 1967; Ayre, 1966). 

These transformed cells were exfoliated, and no alterations were observed 3 weeks after 

application. 

Oral exposure studies in rats and mice (NTP, 1994; McCauley et al., 1985; Schroeder and 

Mitchener, 1975a, b) did not find significant increases in tumor incidence following chronic 

exposure.  The design of the McCauley et al. (1985) and Schroeder and Mitchener (1975a, b) 

studies was inadequate for carcinogenicity evaluation.  In the McCauley et al. (1985) study, 

small numbers of animals of one sex were exposed to relatively low concentrations of barium 

chloride for less than a lifetime.  The absence of adverse effects suggests that the maximum 

tolerated dose (MTD) may not have been achieved in this study.  In the Schroeder and Mitchener 

(1975a) rat study, only the incidence of total gross tumors was reported; the lack of adverse 

effects suggests that the only dose used was lower than the MTD.  The decrease in longevity in 

the mouse study by Schroeder and Mitchener (1975b) suggests that the MTD may have been 

achieved in this study.  However, it appears that only two types of cancer were examined 

(leukemia and lung tumors). 

The design of the rat and mouse NTP (1994) studies was adequate to assess 

carcinogenicity.  These studies used an adequate number of animals per group, exposed animals 

for 2 years, tested several dosage levels, and examined an extensive number of tissues.  The 

decreased survival and histologic alterations in the kidneys of the mice and the increased kidney 

weights in the rats suggest that the MTD was achieved in both of these studies.  No carcinogenic 

effects were observed in either species.  In fact, significant negative trends in the incidence of 

leukemia, adrenal tumors, and mammary gland tumors were observed in the rats. 

The inhalation exposure and intratracheal studies conducted by Tarasenko et al. (1977) 

are inadequate for carcinogenicity evaluation because of several deficiencies in the design and 

reporting, including single or subchronic exposure duration, inadequate reporting of aerosol 

generation methodology, inferior reporting of study results (including the apparent lack of 

statistical analysis), and the use of only one sex (males).  These studies were designed to be 

toxicity studies, and it is not known if the investigators looked for tumors. 

Under EPA’s Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986c), barium 

would be classified as Group D, not classifiable as to human carcinogenicity.  Although adequate 

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