Spacecraft Water Exposure Guidelines for Selected Contaminants Volume 2 (2007) / Chapter Skim
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Appendix 3 Barium and Barium Salts
Appendix 3 Barium and Barium Salts
Pages 52-95
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3 Barium and Barium Salts Raghupathy Ramanathan, Ph.D. NASA-Johnson Space Center Toxicology Group Houston, Texas PHYSICAL AND CHEMICAL PROPERTIES Barium (Ba)
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has reported that the range of daily dietary intake of Ba is 300-1,770 g per day (4-25 μg per kilogram body weight per day)
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In clinical practice, the amount given to adults is not based on body weight; the commercial preparation of preweighed BaSO4 (340 g) is suspended in 150 mL of water.
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, also performed equivalent experiments in 15-month- (mo) old female rats to compare Ba metabolism in humans with that in animals.
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(1981) reported that 10-15% of a radioactive dose of Ba iv injected was excreted in the feces within the first 24 h after dosing; the report noted very similar rates in rats and mice.
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There are wide variations in the amounts reported for Ba absorption as a function of dose that have not been described clearly in the literature. Although several studies have described the cardiovascular effects of Ba, BaSO4 is used extensively in everyday diagnostic radiology without any serious adverse consequences that might cause it to be discontinued.
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undergoing routine Ba enema examinations, 12-lead ECG and 100-cycle cardiac rhythm recordings were performed, in addition to systemic arterial pressure measurements in the supine and upright positions. These tests were done before, during, and after the enema study.
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Infusion by iv of BaCl2 to anesthetized dogs or guinea pigs resulted in increased blood pressure and cardiac arrhythmia (Roza and Berman 1971; Hicks et al.
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At necropsy, male rats that received 300 mg/kg showed ocular discharge, fluid in the trachea, and darkened liver. In addition, inflammation of both the small and large intestines was seen in both the male and female rats at 300 mg/kg.
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No consistent pathologic findings were noted. Decreased body weights and decreased ovary-to-brain weight ratios were noted in female rats.
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, the effects on motor activity, and the significant decreases in water consumption. For renal effects, a LOAEL of 2,000 ppm (Ba at 180-200 mg/kg)
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1981) reported the results of blood pressure and health questionnaire data from a randomly selected pool of subjects.
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No significant differences in mean systolic or diastolic blood pressures or in rates of hypertension, heart disease, stroke, or kidney disease were found between the men and women of the community with increased Ba concentrations and those of the community with low Ba concentrations. In a later analysis of the data, criteria were used for the number of years of residency, use of high blood pressure medications, and use of water softeners.
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Only small reductions were noted in body weights in the 2,500 ppm group. Dose-related decreases in water consumption of about 23% were observed in male and female rats.
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for renal glomerular damage, evidenced as proteinuria, in male rats maintained on low-mineral diets.
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Using measured water consumption and body weights, the authors estimated daily Ba doses for the treated groups at 15, 30, and 60 mg/kg/d for males and 15, 45, and 75 mg/kg/d for females. No chemical-related, noncarcinogenic histologic changes were observed in any organs or tissues.
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Increased mortality, increased leukocyte count, disturbances in liver function, and increased urinary excretion of hippuric acid were observed in offspring of female rats administered BaCO3 at 18.3 mg/kg/d orally during pregnancy (Tarasenko et al.
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extremities Abnormal ECG; <1 d Dogs (iv Hypokalemic and cardiovascular effects; a Roza and BaCl2 48-21 mg/kg infusion combination of ectopic ventricular contractions, Berman study) ventricular tachycardia, etc.; abnormal ECG 1971 Oral gavage; range 1 d Rats, male 95% of effects occurred within 5 h after the dose; Borzelleca BaCl2 of doses from 34 to and female medial lethal doses for male and female rats were et al.
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1989 showed depressed cardiac contractility and conduction Drinking water; 0, 2.75, 4, 8, and Rats, male No hematologic or serum chemistry Tardiff et al. BaCl2 13.7, and 66.25 mg/kg 13 wk and female changes; decreased water consumption in 1980 the high-dose group
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decreased motor activity in both sexes at the highest dose; no cardiovascular-related parameters changed Drinking water; 0 or 0.61 Life-term Rats, male A significant reduction in longevity; Schroeder and Ba and female; proteinurea in male rats at 5 mo; increased Michner 1979 (CH3.COO) 2 mg/kg for mice and 0.25 study mg/kg for rats mice, male serum cholesterol in females and female Abbreviations: BP, blood pressure; BUN, blood urea nitrogen; ECG, electrocardiogram; GI, gastrointestinal; iv, intravenous; NE, norepinephrine.
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Toxicity End Point Data Source 1d 21 Cardiotoxicity Roza and Berman 1971 10 d 21 Cardiotoxicity Roza and Berman 1971 100 d 10 Decreased water consumption Tardiff et al. 1990; NTP 1994 1,000 d 10 Decreased water consumption NTP 1994 spacecraft water exposure guideline (SWEG)
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EPA derived an oral reference dose (RfD) of 0.07 mg/kg/d on the basis of a NOAEL of 7.3 mg/L obtained from the epidemiologic study of Ba exposure from Illinois drinking water supplies (Brenniman et al.
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State of Alabama Drinking water 1.0 mg/L Groundwater 1.0 mg/L District of Columbia Public water supply 1.0 mg/L State of Florida Surface and potable water 1.0 mg/L State of Texas Community water system 1.0 mg/L a While this document was in the final stages of going to the press, NASA learned that EPA has revised the RfD for barium and compounds. According to the revised RfD assessment that was available in July 2005, it has been established that the oral RfD is 0.2 mg/kg/d due to the selection of a new principal study and critical effect, the 2-y NTP drinking water study and nephropathy, respectively, and using benchmark dose modeling.
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Dallas and Williams (2001) identified NOAELs for renal effects from the NTP studies (60 mg/kg/d for male rats, 75 mg/kg/d for female rats, 75 mg/kg/d for male mice, and 90 mg/kg/d for female mice)
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, where 2 = LOAEL-to-NOAEL extrapolation factor; 10 = species extrapolation factor; and 5 = spaceflight factor and for cardiotoxicity and other effects on muscle contraction.
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÷ (10 × 2.8 L/d) = 165 mg/L, where 70 kg = nominal body weight; 10 = species extrapolation factor; and 2.8 L/d = nominal water consumption.
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, where 60 mg/kg/d = NOAEL; 70 kg = nominal body weight; 10 = species extrapolation factor; 2.8 L/d = nominal water consumption; and 3 = spaceflight factor for dehydration. The 10-d short-term toxicity study by Borzelleca et al.
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In the NTP (1994) BaCl2 drinking water study, BUN was not altered in male or female rats.
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, where 9.7 mg/kg /d = NOAEL; 70 kg = nominal body weight; 10 = species extrapolation factor; 2.8 L/d = nominal water consumption; 3 = spaceflight factor for dehydration; and 100 d/91 d = time extrapolation factor. A benchmark dose (BMD)
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, where 65 mg/kg/d = NOAEL; 10 = species extrapolation factor; 70 kg = nominal body weight; 2.8 L/d = nominal water consumption; 100 d/91 d = time factor for extrapolation; and 3 = spaceflight factor to further protect against renal effects and bone demineralization. In the 13-wk subchronic toxicity NTP study (1994)
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) = 75 mg/L, where 32.5 mg/kg/d = BMDL01; 70 kg = nominal body weight; 10 = species extrapolation factor; 2.8 L/d = nominal water consumption; and 100 d/91 d = time extrapolation factor.
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No prior medical history of these individuals before they migrated into this region is known. In a follow-up study, no significant differences were observed in the mean systolic and diastolic blood pressures of men or women between the two communities.
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÷ (70 kg × 3) = 0.07 mg/kg/d, where 2 L/d is the nominal water consumption, 70 kg is the nominal body weight, and 3 is the factor to reduce the NOAEL.
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× 3) = 9 mg/L, where 15 mg/kg/d = LOAEL; 70 kg = nominal body weight; 10 = species extrapolation factor; 2.8 L/d = nominal water consumption; 1,000 d/730 d = time factor; and 3 = spaceflight factor for dehydration.
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× 3) , where 70 kg = nominal body weight; 10 = species extrapolation factor; 2.8 L/d = nominal water consumption; 1,000 d/730 d = time extrapolation factor; and 3 = spaceflight safety factor for renal effects risk and bone demineralization risks.
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(mg/L) Mice, male BMDL01 24 19 Mice, male NOAEL 46 45 Mice, female BMDL01 46 37 Mice, female NOAEL 55 54 a The following common factors were used for both: 70 kg = nominal body weight; 2.8 L/d = nominal water consumption; 10 = species extrapolation factor; 1,000 d/730 d = time extrapolation factor; and 3 = spaceflight factor for renaleffects risk and bone-demineralization risks.
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; thymic and 13 wk; drinking and 91) spleen atrophy in male water female and female mice Neurobehavioral effects NOAEL = 110; Rats, male 1 10 (100/ 1 -- -- 250 -- NTP 1994 (motor activity)
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; female 2 y; BaCl2 in drinking water Reduced water 3 -- -- -- 9 NTP 1994 NOAEL = 15; 2 Rats 1 10 1.37a consumption y; drinking water Mice, 1 10 1.37a 3 -- -- -- 24 NTP 1994 Renal Crystal formation BMDL01 = 40; 2 y; BaCl2 in male drinking water Nephropathy 1 10 1.37a 3 -- -- -- 19 NTP 1994 BMDL01 = 32; 2 Mice, male y; BaCl2 in drinking water SWEGb 21 21 10b 10b a Factor for time extrapolation from 730-d to 1,000-d. b These values were rounded to 10 for both 100- and 1,000-d ACs.
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of barium chloride in male and female rats.
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1992. Subchronic toxicity of barium chloride dihydrate administered to rats and mice in the drinking water.
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1985. The secretory action of barium chloride in rat colon.
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1994. Technical report on the toxicology and carcinogenesis studies of barium chloride dihydrate (CAS No.10326
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1975. Incidence of arrhythmias and ST-segment changes in elderly patients dur ing barium enema studies.
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1981. Acute renal failure associ ated with barium chloride poisoning.
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