Toxicological Review of Barium and Compounds

years, examined in this study lived in the community for more than 10 years; thus, it is 

probable that the study included individuals who were exposed to elevated barium levels 

as children.  However, this study may not account for all of the uncertainty that there may 

be differences between children and adults.  The Agency feels that the current RfD would 

be protective for children. 

Comment:  One reviewer was uncomfortable with the apparent dismissal of the increased 

calcium levels observed in the Wones et al. (1990) human experimental study. 

Response to Comment:  EPA feels that the slight increase in albumin-corrected serum 

calcium levels is not clinically significant.  The adjusted serum calcium levels were 8.86, 

9.03, and 9.01 mg/dL when the subjects were exposed to 0, 5, or 10 ppm barium, 

respectively.  The Agency feels that this small change in calcium levels is not likely to 

result in adverse effects.  In addition, studies in animals have shown no changes in serum 

calcium levels following short-term or chronic exposure to barium in drinking water 

(NTP, 1994; Tardiff et al., 1980).  The Wones et al. (1990) study description in the 

document and RfD summary sheet was revised to include the serum calcium levels 

(adjusted and unadjusted levels were reported) and a note that the adjusted method used 

by Wones et al. (1990) is considered unreliable. 

Comment:  One reviewer expressed concern that the apparent barium-related increased 

mortality observed in the mortality portion of the Brenniman and Levy (1984) study was 

discounted. 

Response to Comment:  EPA feels that it is not possible to assign a causal relationship 

between mortality and exposure to barium based on the results of this study because a 

number of potentially confounding variables were not controlled. 

Comment:  One reviewer noted that the finding of impaired lung function in >20% of the 

workers examined by Doig (1976) is not an inconsequential finding. 

Response to Comment:  Five workers underwent lung function tests in 1963 (exposure 

was terminated in 1964).  For three of the workers, the results were similar to predicted 

values (89%-119% of predicted values).  Lung function tests were below predicted 

values (70%-85%) in the other two workers.  The study authors noted that the impaired 

lung function was not likely due to barium exposure (one worker was an alcoholic and 

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heavy smoker and the second worker had a fibrotic lung resulting from an early 

childhood illness).  The Toxicological Review was revised to include lung function 

performance results and possible cause of the impaired lung function in the two workers. 

Comment:  One reviewer felt the discussion of why the data were inadequate for derivation of 

an RfC should be expanded, and the reviewer noted that the NIOSH (1982) study did report 

some breathing zone air barium levels. 

Response to Comment:  EPA feels that the inhalation data base limitations are 

adequately discussed.  The text was revised to note that 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. 

REFERENCES FOR APPENDIX A-1 

Brenniman, GR; Levy, PS. (1984) Epidemiological study of barium in Illinois drinking water supplies. In: Advances 

in modern toxicology. Calabrese, EJ, ed. Princeton, NJ: Princeton Scientific Publications, pp. 231-240. 

Doig, AT. (1976) Baritosis: a benign pneumconiosis.  Thorax 31:30-39. 

National Institute for Occupational Safety and Health (NIOSH), Public Health Service, U.S. Department of Health 

and Human Services. (1982) Health hazard evaluation report no. 81-356-1183, Sherwin Williams Company, 

Coffeyville, KS. Health Evaluation and Technical Assistance Branch, Cincinnati, OH. 

National Toxicology Program (NTP), Public Health Service, U.S. Department of Health and Human Services. (1994) 

NTP technical report on the toxicology and carcinogenesis studies of barium chloride dihydrate (CAS no. 10326-27-

9) in F344/N rats and B6C3F1 mice (drinking water studies). NTP TR 432. Research Triangle Park, NC. NIH pub. 

no. 94-3163. NTIS PB94-214178. 

Tardiff, RG; Robinson, M; Ulmer, NS. (1980) Subchronic oral toxicity of BaCl

2

 in rats. J Environ Pathol Toxicol 

4:267-275. 

U.S. EPA (1994) Peer review and peer involvement at the U.S. Environmental Protection Agency, signed by U.S. 

EPA Administrator Carol Browner, dated June 7, 1994. 

U.S. EPA (1998c) Toxicological Review of Barium and Compounds.  Available from IRIS Hotline, Washington, DC 

[phone]. 

Wones, RG; Stadler, BL; Frohman, LA. (1990) Lack of effect of drinking water barium on cardiovascular risk 

factor. Environ Health Perspect 85:355-359. 

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APPENDIX A-2.  SUMMARY OF 2004 EXTERNAL PEER REVIEW AND PUBLIC 

COMMENTS AND DISPOSITION 

In May 2004, the draft document entitled “Proposed Oral Reference Dose (RfD) for 

Barium and Compounds” was externally peer reviewed.  The peer review was conducted by Oak 

Ridge Institute for Science Education under contract with U.S EPA.  The five expert reviewers 

(names and affiliations are provided in the preface) were charged to address 10 questions. The 

list of charge questions, a summary of comments made by the external reviewers and the public, 

and EPA’s responses to these comments follow. 

Charge to External Reviewers 

A. Principal Study

The National Toxicology Program (NTP) (1994) chronic rodent study was selected as the 

principal study for the derivation of the proposed barium RfD.  

A1) 

Is the NTP (1994) chronic animal study the most appropriate and scientifically 

justifiable principal study for deriving the RfD?  If not, what other study (or 

studies) should be chosen and why? 

A2) 

Is the explanation for why the human studies were not used as coprincipal 

studies transparent and scientifically objective?  

A3) 

Are you aware of any other studies that may be relevant to the derivation of the 

RfD? 

B. Critical Effect

Renal lesions (nephropathy) in mice were identified as the critical effect for deriving the 

proposed RfD. 

B1) 

Are renal lesions (nephropathy) the most appropriate critical effect for deriving 

the RfD?  Points relevant to this determination include whether this effect 

demonstrated a suitable dose-response relationship and whether the effect is 

considered adverse.  Are these issues objectively and transparently described? 

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