Toxicological Review of Barium and Compounds

rodent studies.  The data base is deficient in several areas: neither a two-generation reproductive 

toxicity study nor an adequate investigation of developmental toxicity has been conducted.  It is 

also not known if barium deposition in bone tissue is associated with an adverse effect.  The 

available data indicate that renal toxicity is likely to be the most sensitive endpoint for chronic 

barium exposure. 

An UF was not needed to account for subchronic-to-chronic extrapolation because a 

chronic study was used to derive the RfD.  An UF for LOAEL-to-NOAEL extrapolation was not 

used since benchmark dose modeling was employed to determine the point of departure.  

The RfD for barium (reported as one significant figure) was calculated as follows: 

RfD  =  BMDL

05

 ÷ UF  =  63 mg/kg-day ÷ 300  =  0.2 mg/kg-day (2×10

-1

 mg/kg-day) 

5.1.4.  Previous Oral Assessment 

The previous IRIS assessment (U.S. EPA, 1998c) contained an RfD of 7×10

-2

 mg/kg-day, 

which was based on a weight-of-evidence approach that encompassed four co-principal studies: 

Wones et al. (1990), an experimental study in humans; Brenniman and Levy (1984), a 

retrospective epidemiologic study; and subchronic and chronic rat studies (NTP, 1994). 

Hypertension and renal effects were designated as co-critical effects.  Evidence of hypertension 

was not observed in any of the co-principal studies, and as a result the highest exposure levels in 

the two human studies were defined as NOAELs.  These NOAELs, which coincidently were 

identical (0.21 mg/kg-day), were divided by an uncertainty factor of 3 to derive the RfD.  This 

uncertainty factor was applied to account for some data base deficiencies and concerns about the 

potential differences between adults and children.  Increased kidney weight in male rats with a 

NOAEL of 45 mg/kg-day (NTP, 1994) was referenced as a supporting study but was not used in 

the derivation of the RfD. 

5.2.  INHALATION REFERENCE CONCENTRATION 

The human (Seaton et al., 1986; Doig, 1976; Pendergrass and Greening, 1953) and 

animal inhalation (Tarasenko et al., 1977) and intratracheal (Uchiyama et al., 1995; Tarasenko et 

al., 1977) studies suggest that the respiratory system is a target of barium toxicity.  The data also 

suggest that systemic effects, such as hypertension, may occur following inhalation exposure 

(Zschiesche et al., 1992; NIOSH, 1982; Tarasenko et al., 1977).  The human studies cannot be 

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used to derive an RfC for barium because exposure concentrations were not reported.  Although 

the NIOSH (1982) study measured barium breathing zone levels for some groups of workers, the 

barium exposure levels were not measured in the group of workers with the increased incidence 

of hypertension.  The deficient reporting of the methods and results (in particular, the lack of 

information on the aerosol generation, number of animals tested, incidence data, and statistical 

analysis) of the only animal subchronic/chronic inhalation study (Tarasenko et al., 1977) 

precludes deriving an RfC for barium from the animal data. 

5.3.  CANCER ASSESSMENT 

The oral database suggests that barium is unlikely to be carcinogenic to humans, and the 

inhalation database is inadequate to assess carcinogenicity.  Thus, derivation of slope factors and 

unit risk values is precluded. 

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6.  MAJOR CONCLUSIONS IN THE CHARACTERIZATION OF 

HAZARD AND DOSE-RESPONSE 

6.1.  HAZARD IDENTIFICATION 

Barium is a dense alkaline earth metal that is widely distributed in small amounts in the 

earth’s crust.  Under natural conditions, barium occurs as the divalent cation in combination with 

other elements.  Barium enters the environment through the weathering of rocks and minerals 

and through anthropogenic releases.  Barium toxicity is produced by the free cation, and highly 

soluble barium compounds are more toxic than insoluble compounds, such as barium sulfate. 

Intentional or accidental human ingestion of barium compounds causes gastroenteritis, 

hypokalemia, acute hypertension, cardiac arrhythmias, skeletal muscle paralysis, and death 

(CDC, 2003; Jourdan et al., 2001; Downs et al., 1995; Tenenbein, 1985). 

Investigations of chronic barium toxicity in humans have focused on cardiovascular 

toxicity, with a specific emphasis on hypertension.  A chronic dose of barium capable of 

producing cardiovascular toxicity has not been identified (Wones et al.,1990; Brenniman et al., 

1981).  The NOAEL for both Brenniman et al. (1981) and Wones et al. (1990) was estimated by 

EPA to be 0.21 mg/kg-day using standard estimates for drinking water intake (2 L/day) and 

average body weight (70 kg).  However, low confidence is placed in these NOAELs because 

they are not linked to an adverse effect level and because of limitations in the designs of these 

studies. 

Increased blood pressure and cardiac arrhythmias have been reported in anesthetized 

dogs and guinea pigs receiving intravenous infusions of barium chloride (Hicks et al., 1986; 

Roza and Berman, 1971).  Perry et al. (1989, 1985) are the only studies to report hypertension in 

animals following subchronic exposure to barium.  The rats in these studies were maintained on 

a rye-based diet with a calcium content below the recommended daily requirement (NRC, 1995), 

lower in potassium than standard rat chow.  Animals maintained on diets low in calcium or 

potassium may be more sensitive to the cardiovascular effects of barium.  In view of a possible 

association between the barium-induced cardiovascular effects and calcium and potassium 

intake, the relevance of the data from Perry et al. (1989, 1985) to animals maintained on standard 

diets or humans is uncertain.  NTP (1994) evaluated blood pressure and EKG readings of rats 

exposed to barium in drinking water for 13 weeks.  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) observed no adverse effect on blood pressure 

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