3
Barium and Barium Salts

Raghupathy Ramanathan, Ph.D. NASA-Johnson Space Center Toxicology Group Houston, Texas

PHYSICAL AND CHEMICAL PROPERTIES

Barium (Ba) salts have a range of solubilities in water. Ba metal is insoluble in water but soluble in alcohol. The three least soluble Ba salts are the sulfate, the carbonate, and the sulfide. The acetate, the cyanide, the chloride, and the nitrates and alkaline salts, such as the oxides and hydroxide, are highly soluble in water (see Table 3-1), some even at 0°C. In general, the acid-soluble Ba salts are very toxic when compared with the least soluble salts, such as Ba sulfate (BaSO4).

OCCURRENCE AND USE

Ba is one of the alkaline earth metals. It occurs in nature as a free metal and as salts. It is also produced for various industrial uses. The Ba salt most commonly found in the earth’s crust is BaSO4, which is found in limestone (barite), shales, and rocky sediments. In a crushed form, it is the source for several other Ba compounds.

The major use of BaSO4 is in the oil and gas industry to make lubricant muds for drilling. Ba in salt forms has been reported to be present in almost all surface waters (at 2-340 micrograms per liter [g/L]) (Kopp and Kroner 1967). The release of Ba compounds from Ba manufacturing and processing plants and from sedimentary rocks by leaching in certain areas might be the reason for its presence in surface waters. The finished water of public systems frequently contains Ba at 1-172 g/L (Tuovinen 1980). A mean concentration of 43 g/L and a maximum of 380 g/L were reported in the largest U.S. cities (NRC 1977, pp. 229-230)



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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 3 Barium and Barium Salts Raghupathy Ramanathan, Ph.D. NASA-Johnson Space Center Toxicology Group Houston, Texas PHYSICAL AND CHEMICAL PROPERTIES Barium (Ba) salts have a range of solubilities in water. Ba metal is insoluble in water but soluble in alcohol. The three least soluble Ba salts are the sulfate, the carbonate, and the sulfide. The acetate, the cyanide, the chloride, and the nitrates and alkaline salts, such as the oxides and hydroxide, are highly soluble in water (see Table 3-1), some even at 0°C. In general, the acid-soluble Ba salts are very toxic when compared with the least soluble salts, such as Ba sulfate (BaSO4). OCCURRENCE AND USE Ba is one of the alkaline earth metals. It occurs in nature as a free metal and as salts. It is also produced for various industrial uses. The Ba salt most commonly found in the earth’s crust is BaSO4, which is found in limestone (barite), shales, and rocky sediments. In a crushed form, it is the source for several other Ba compounds. The major use of BaSO4 is in the oil and gas industry to make lubricant muds for drilling. Ba in salt forms has been reported to be present in almost all surface waters (at 2-340 micrograms per liter [g/L]) (Kopp and Kroner 1967). The release of Ba compounds from Ba manufacturing and processing plants and from sedimentary rocks by leaching in certain areas might be the reason for its presence in surface waters. The finished water of public systems frequently contains Ba at 1-172 g/L (Tuovinen 1980). A mean concentration of 43 g/L and a maximum of 380 g/L were reported in the largest U.S. cities (NRC 1977, pp. 229-230)

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 TABLE 3-1 Physical and Chemical Properties of Ba and Ba Compounds Compound Form Molecular Weight Solubility Comment Ba Ba 137.3 Insoluble in water; soluble in alcohol Ba chloride BaCl2 208.2 375 g/L at 26°C 65.95% Ba Ba chloride dehydrate BaCl2·2H2O 244.3 375 g/L at 26°C 56.2% Ba Ba acetate Ba(CH3COO)2 255.5 1 g/1.5 mL 53.77% Ba Ba sulfate BaSO4 233.4 1.6 mg/L at 20°C Also known as “barite”; 58.84% Ba Ba carbonate BaCO3 197.37 20 mg/L at 20°C 69.58% Ba Ba sulfide BaS 169.42 1.1 mg/L 81.08% Ba Ba nitrate Ba(NO3)2 261.38 Freely soluble 52.55% Ba Source: Data from Merck 1989. McCabe et al. (1970) and Calabrese (1977) reported that Ba was present in about 2,600 analyzed drinking water samples. It was found at about 1.5 milligrams (mg) per L in samples from areas of northern Illinois and northern Iowa. Because the solubility of Ba depends on the concentrations of total sulfate in the medium and because sufficient concentrations of sulfates are in the natural waters, it is difficult to maintain more than 1.5 mg/L in water (EPA 1985). The World Health Organization (WHO) 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). WHO (1990) also reported that the concentrations of Ba measured in U.S. drinking waters are 1-20 g/L. Several other reports indicated that the concentrations are much higher (Kopp 1969; Calabrese 1977). Ba compounds are used to make not only drilling lubricants but also paints and pigments, textile dyes, greases, bricks, tile, glass, and rubber. Ba nitrate (Ba(NO3)2) is used in pyrotechnics. Because of its high radiopacity, BaSO4 has been used by doctors for taking x-rays of the stomach, intestines, and respiratory and urinary tract systems and in bronchography. A high-density suspension of Ba sulfate—usually 340 g suspended in 150 mL of water—is administered orally for radiologic evaluation of the small bowel. This represents a dose of 4.89 g per kilogram (kg).

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 Humans might be exposed to Ba at high concentrations in occupational settings or in areas proximate to Ba mining and processing. PHARMACOKINETICS AND METABOLISM Absorption Only very scanty human data are available on the absorption of Ba and its salts from the gastrointestinal (GI) tract. Lisk et al. (1988) studied the absorption and excretion of selenium and Ba in humans who consumed Brazil nuts, which contain both. The nuts they used contained Ba at 1,953 parts per million (ppm). As part of the study, one male subject (68 kg) ingested nut meat equivalent to Ba at 179.2 mg (2.64 mg/kg) in a single dose. Total urine and feces for each day was collected for 15 days (d) after the dose. From the total amount of Ba excreted in feces and urine, which was only 10% of the ingested dose, it appears that 90% of the dose was absorbed. This is the highest percentage ever reported for Ba absorption. It is not clear what form of Ba is contained in Brazil nuts or how other materials, including fat, would have facilitated such a high absorption. The absorption rate was estimated to be 5% in the adult (ICRP 1973) on the basis of results from two human volunteers. It has also been suggested that infants might have significantly greater absorption rates than adults (Lengemann 1959). For radiologic examination of the small bowel, a solution of Baricon, a highly insoluble suspension of BaSO4 at about 4.89 g/kg, or Ba at 2.88 g/kg, is usually administered to patients. 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. According to the Merck Index (Merck 1989), BaSO4 is practically insoluble in water (1 g in 400,000 parts), dilute acid, and alcohol. It is soluble only in hot, concentrated sulfuric acid. In the above example, the 150 mL of water dissolves BaSO4 at only 0.375 mg (Ba at 0.003 mg/kg). Neither the pH of stomach acid nor the alkalinity of the intestinal contents contributes to the solubility of ingested BaSO4 used in the clinical setting. Dallas and Williams (2001) cited a study from a student thesis (Bligh 1960) in which isotopic Ba was given intravenously (iv) or given in orange juice as an oral dose to cancer patients. Feces and urine samples were collected for 7-10 d, and radioactivity was deter-

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 mined. Bligh 1960, as cited in Dallas and Williams (2001), also performed equivalent experiments in 15-month- (mo) old female rats to compare Ba metabolism in humans with that in animals. The study concluded that an average of 9% of radioactive Ba was absorbed in humans and about 10% in rats. In laboratory animals, absorption varies significantly with species, age, and composition of the diet. For example, Taylor et al. (1962) reported that although older rats absorbed 7% of ingested Ba chloride (BaCl2), the amount absorbed by rats 22 d old or younger was at least 10 times higher. Fasted adult rats absorbed about 20%. GI absorption in dogs has been calculated to be about 7% (Cuddihy and Griffith 1972). Measurements of Ba in the serum of dogs indicate that peak absorption from the GI system occurs within 1 h (Chou and Chin 1943). McCauley and Washington (1983) examined the effect of oral intubation of various anions of the Ba salt on the relative rates of uptake and tissue deposition in rats. Male Sprague-Dawley rats weighing 250-300 g were maintained on a diet of Ba at less than 1 mg/kg of food for at least 1 mo before the experiment. They were orally administered 131Ba as sulfate (SO4), chloride (Cl), or carbonate (CO3) at pH 7.0 (0.5 mL/100 g body weight of a 10 mg/L solution). Animals sacrificed at 2, 5, 10, 20, 30, 60, and 120 minutes (min) and 24 hours (h) after intubation. Amount of radioactivity was measured in the blood and various tissues at various intervals. One group of animals was also intubated with 131Ba as the chloride anion (BaCl2) after the 24-h fast and studied at various times thereafter. With 131BaCl2, in the nonfasted rats, the maximum concentrations of 131Ba in blood was reached in 60 min, and at 24 h, the activity was about 90% of the maximum value, indicating a very slow rate of elimination. However, in the fasted rats, the peak radioactivity was measured at 15 min, and the radioactivity after 4 h was only 50% of the peak activity, indicating that fasting can affect both the rate of absorption and elimination. In the nonfasted rats, when 131Ba was intubated as the sulfate of the carbonate anion, the peak radioactivity in the blood was reached at 60 min, similar to the nonfasted BaCl2 group. The authors stated that when large oral doses of BaSo4 are used in radiopaque x-ray diagnosis, only a very small fraction is absorbed. No overt toxic effects have been reported from “Ba swallows” (BaSO4 administered orally) during diagnostic procedures.

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 Distribution From the available studies on the distribution of Ba in the human body, it appears that Ba distributes mostly (over 93% of the body burden) in the bones and teeth and to a small extent, in the eye, lungs, skin, and adipose tissue in humans at less than 1% of total body weight (Schroeder et al. 1972; ATSDR 1992). From autopsy data, Sowden and Stitch (1957) reported that the Ba concentrations in human bones ranged from 7 ppm in children (0-3 y) to 8.5 ppm in adults (33-74 y), indicating no age-related accumulation. In mice iv injected with 131BaCl2, the radioactivity was localized primarily in the bones, although distribution into other tissues was also observed (Dencker et al. 1976). Twenty-four hours after 131Ba (as 131BaCl2) intubation, the 131Ba concentration measured in five tissues (activity per g tissue weight) was in the order: heart > eye > skeletal > muscle > kidney > liver. The concentration in the cardiac muscle was at least threefold higher than that of the eye. In addition, the accumulation of radioactivity in the eye from the BaSO4 and the BaCl2 groups were similar in the BaCO3-intubated rats; it was 50% of that of the BaCl2-treated group (McCauley and Washington 1983). The radioactivity in the bones was not reported. Excretion In several studies, radioactive Ba was iv injected for the evaluation of the kinetics profile in urine and feces. In humans, the main excretion route for ingested Ba is the feces (about 72%); about 3% is excreted in the urine (Tipton et al. 1966). Harrison et al. (1967) reported that when 133Ba was iv injected to one healthy 60-y-old man, 9% of the injected dose was excreted in the urine and 84% was excreted in the feces. In another study by the same authors, cumulatively 20% of the injected dose was excreted in urine and feces in 24 h, 70% in 3 d, and about 85% after 10 d (Tipton et al. 1966). The excretion half-life was about 35 h. According to the National Research Council (NRC) (1977), 20% of ingested Ba is excreted in the feces and 7% in the urine within 24 h. In dogs that received Ba by gavage, most of the Ba was excreted within a few days (Cuddihy and Griffith 1972). Syed et al. (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. In one study, it was reported that rats and humans excreted Ba in

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 comparable ways, and fecal excretion of Ba was found to be greater than urinary excretion (Bligh 1960, as cited in Dallas and Williams 2001). Approximately 0.5% of the Ba dose was excreted into bile within 2 h in bile-duct-cannulated Sprague-Dawley rats iv injected with 133BaCl2 at 1.8 µg. In parallel to plasma concentrations, biliary Ba concentrations reached their peak in the first 15 min after administration and rapidly declined thereafter; Ba was not concentrated in the liver. Biliary excretion is not important for elimination when Ba is ingested (Edel et al. 1981). The kinetics of Ba elimination appear to have three phases. Rundo et al. (1967) estimated that the half-times of 133Ba for these phases were 3, 6, 34.2, and 1,033 d. TOXICITY SUMMARY A review of the literature on pharmacokinetics (absorption, distribution, and elimination) and toxicity (described in the sections below) indicates that there are several complexities in those areas. For example, although BaSO4 is considered extremely insoluble in water, some studies comparing uptake kinetics could not differentiate BaSO4 from highly soluble Ba compounds. 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. Acute Toxicity (<1 d) Ba, like other alkaline earth metals, is a bone-seeking element (Bauer et al. 1957), but its function in bone is not known. Ba can replace calcium and can carry out several calcium-mediated effects, such as the release of adrenal hormones and of neurotransmitters from adrenergic synapses (Douglass and Rubin 1964). Ba can also release catecholamines in the absence of acetylcholine. The most studied effects of Ba toxicity are vasoconstriction, hypertension, and those that occur in the muscular system. These end points have been the focus of several investigations of chronic low-dose exposure. Several studies conducted in the late 1960s and early 1970s suggest that electrocardiogram (ECG) abnormalities were encountered during Ba

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 enema x-rays of older patients and patients with heart diseases. ECG abnormalities were pronounced in patients over the age of 60. Minor ECG abnormalities occurred in the lower age range in patients over 60 y of age (Berman et al. 1965; Eastwood 1972). In 1975, Roeske et al. studied patients over 60 and reported potentially serious effects such as incidence of arrhythmias and ST-segment changes during Ba enema x-ray studies. In 58 unselected, consecutive patients (ages 60-98 y old) 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. Subsequent ST-segment changes were also analyzed from the ECG recordings. In 27 of the 58 patients, abnormal ECG recordings (positive alterations as defined by stated criteria) were noted. Twenty-three patients developed significant arrhythmias during the Ba enema, four exhibited new ST-segment depressions, and 31 patients had negative results. The significant observations were that patients who were taking digitalis (an anti-arrhythmia medication) did not exhibit positive ECG alterations, whereas patients who were not receiving digitalis exhibited positive results. Furthermore, randomly chosen patients who received an iv dose of glucagon to prevent intestinal spasms did not respond differently from those who did not receive glucagon. This indicated that atrial arrhythmias and ST-segment changes might not be because of Ba-induced GI spasms. Blakeborough et al. (1997) reported the results of a 1992-1994 survey, including questionnaires completed by U.K. consultant radiologists, of complications of Ba enema examinations in 750,000 patients. An overall mortality of about 1 in 57,000 was reported. A total of 82 complications (contraindications) were reported. Of 16 patients observed to have cardiac arrhythmias, 9 died. Seven of the nine patients who died were over the age of 75. Only a few of the other patients had a previous history of cardiac problems. BaSO4, the insoluble salt of Ba, was used. There were no reported cases of such effects from Ba swallows during radiologic examinations. Thus, Ba-induced cardiac arrhythmias seem to occur only during enemas in extremely few cases, and patients over age 70 appear to be more susceptible if they have a prior documented history of cardiac disease. Because these patients had a health condition that warranted such a diagnostic procedure, application of these results to normal healthy populations could be limited. In general, the toxicity of soluble Ba salts is far greater than that of insoluble forms (NRC 1977) when administered orally. Profound changes in cardiac, skeletal, and smooth-muscle functions resulting from

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 acute and accidental ingestion of soluble Ba salts have been reported. Several investigators (Roza and Berman 1971; Talwar and Sharma 1979; Wetherill et al. 1981) have reported cases of hypertension, paralysis of skeletal muscle, and cardiac arrests due to ingested soluble Ba salts. 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. 1986). The study also reported skeletal muscle flaccidity and paralysis in dogs (Roza and Berman 1971). Although extremely rare, anomalies of cardiac rhythm during the Apollo and Skylab missions (Leguay and Seigneuric 1981) and episodes of ventricular tachycardia during long-duration missions (Fritsch-Yelle et al. 1998, see also readers’ notes in Ellestad 1999) have been reported. On the basis of those findings, there is concern that ingestion of Ba could potentiate such effects during short- and long-duration missions. There have been numerous case reports of humans exposed to Ba through accidental or intentional oral ingestion. Death occurred in six cases of accidental or intentional ingestion of Ba salts. Two deaths were attributed to cardiac arrest (one from severe GI hemorrhage), and in three cases, the specific cause was not determined (Ogen et al. 1967; Das and Singh 1970; Talwar and Sharma 1979). Several cases of food poisoning from Ba carbonate were reported by Lewi and Bar-Khavim (1964) and Diengott et al. (1964). Symptoms of gastroenteritis, a feeling of numbness, diarrhea, vomiting, muscular twitching, and paralysis resulted from ingesting meat contaminated with BaCO3. Of all cases, 5-10% were fatal within the first 48 h. In two patients, flaccid paralysis was found to be because of hypokalemia caused by low-serum potassium, and ECG recordings showed typical hypokalemic changes. Administration of potassium changed the clinical course or accelerated recovery from Ba poisoning, indicating that at least some of the effects are the result of hypokalemia. The acute oral LD50 (dose lethal to 50% of subjects) for Ba varies with species, compound, and age. For example, in the rat and guinea pig, the LD50 for BaCl2 is 118 and 76 mg/kg, respectively (Sax 1984). In humans, the lowest dose that caused death (LDLO) for BaCl2 is 11.4 mg/kg, while it is 70, 170, and 90 mg/kg in the mouse, rabbit, and dog, respectively (Sax 1984). Mortality has been observed in experimental animals following acute and chronic oral exposures to BaCl2 and Ba acetate (Ba(CH3COO)2) (Schroeder and Mitchener 1975; Tardiff et al. 1980; Borzelleca et al. 1988). The acute oral LD50 values for female and male rats were determined to be 269 and 277 mg/kg, respectively (Borzelleca et al. 1988), after the rats were gavaged with BaCl2 in water at doses

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 ranging from 60 to 960 mg/kg (Ba at 40-640 mg/kg). Primary necropsy indicated hemorrhagic areas in the stomach and inflammation of the intestines. Tardiff et al. (1980) initially conducted an acute oral toxicity study of BaCl2 in adult (60-70 d old) and weanling (21-25 d old) male and female rats to determine the LD50 for each group. The acute oral LD50 values were calculated to be 132 mg/kg in the adult rats and 220 mg/kg in the weanling rats. Syed and Hosain (1972) reported LD50 values for different Ba salts administered via iv to two strains of mice (ICR and Swiss-Webster). For the chloride, nitrate, and acetate, the LD50 values were in the ranges of 8.12-11.32 mg/kg for the Swiss-Webster mice and 19.2-23.31 mg/kg for the ICR mice. The values for BaCl2, Ba(NO3)2, and Ba(CH3COO)2 did not vary appreciably, although BaCl2 was the most toxic. Because of the wide variation in the absorption of Ba salts, these values cannot be extrapolated to oral doses. In a 1-d exposure study, Borzelleca et al. (1988) gavaged rats with BaCl2 at 30, 100, and 300 mg/kg after a 24-h fast. A decrease in body weight, liver-to-brain weight ratios, and increases in kidney weight as a percentage of body weight were noted only at the highest dose. It appears that 100 mg/kg is a no-observed-adverse-effect level (NOAEL) for 1 d. Changes that occurred in the clinical chemistry were not dose related. 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. On the basis of these findings, BaCl2 at 100 mg/kg (equivalent to elemental Ba at 66 mg/kg) was identified as a NOAEL. Infusion via iv of BaCl2 to anesthetized dogs (Roza and Berman 1971) or guinea pigs resulted in increased blood pressure and cardiac arrhythmia (Hicks et al. 1986). Roza and Berman (1971) conducted a study on intact, anesthetized mongrel male and female dogs to elucidate the mechanisms of Ba-induced hypokalemia and hypertension and the interaction of Ba and potassium in the hearts of dogs in vivo. The interesting observations in this study were hypertension, a decrease in plasma potassium and an increase in red-cell potassium (shift in the potassium from extracellular to intracellular water) that caused hypokalemia, and myocardial toxicity resulting from hypokalemia. Increased mean corpuscular-red-cell volume (23% increase) leading to a substantial increase in hematocrit was also observed. In part of the study, seven dogs were iv infused with BaCl2 at two rates of infusion (one dog at 1 micromole [µmol]/kg/min and six more dogs at 2 µmol/kg/min). ECG changes were tracked. The cessation of infusion was determined by the appearance of

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 an abnormal ECG. Although an increase in blood pressure was invariably seen during the first 5-10 min of infusion, it subsided 30-40 min after the infusion was finished. Although this was an iv-infusion study, one can attempt to extrapolate to an oral dose using an oral-absorption factor. There is no NOAEL, but the appearance of an abnormal ECG is considered a lowest-observed-adverse-effect level (LOAEL). Short-Term Toxicity (2-10 d) In a separate study by Borzelleca et al. (1988), male and female Sprague-Dawley rats (22-30 d old, 10 per group) were gavaged with BaCl2 in deionized water at 100, 145, 209, or 300 mg/kg for 10 d (doses of Ba at 66, 96,138, or 198 mg/kg/d). Mortality of the female rats in the 198 mg/kg group increased, and one male rat from the 209 mg/kg group died. No consistent pathologic findings were noted. Decreased body weights and decreased ovary-to-brain weight ratios were noted in female rats. Decreased blood urea nitrogen (BUN) was observed in females in all treated groups but was observed in males only at the highest dose. Male rats showed a decrease in leukocytes at 209 mg/kg but not at the higher dose. The significant differences in BUN at all doses in female rats indicate that female rats are more sensitive to the short-term toxic effects of BaCl2. A dose of Ba at 66 mg/kg appears to be a LOAEL for changes in BUN. The clinical significance of the extent of the change observed in this study is questionable. Subchronic Toxicity (11-100 d) In a human study conducted by Wones et al. (1990), 11 male volunteers (ranging in age from 27 to 61 y of age) with no history of hypertension, diabetes, or any cardiovascular disease participated in a 10-week (wk) protocol. The subjects consumed plain drinking water at 1.5 L/d for the first 2 wk. That was followed by 4 wk of consuming 1.5 L of water containing Ba as BaCl2 at 5 ppm/d; and that was followed by 4 wk of consuming 1.5 L/d of water containing Ba as BaCl2 at 10 ppm. The subjects were on a controlled basal diet (dietary contribution of Ba was assumed to be 0.75 mg/d). ECGs and 24-h continuous ECG monitoring were performed. The treatments did not result in any apparent changes in blood pressure, cholesterol, triglyceride, glucose, or potassium concentrations. According to the findings of the Wones et al. (1990) study, a

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 dose of 10 mg/L (equivalent to a dose of Ba at 0.21 mg/kg/d and water consumption at 1.5 L/d) can be considered a NOAEL for adverse effects of Ba in humans exposed for 4 wk. Tardiff et al. (1980) exposed male and female Charles River rats to Ba (as BaCl2) at 0, 10, 50, or 250 ppm in drinking water for 4, 8, or 13 wk. The estimated doses ranged from 1.7-45.7 mg/kg/d. For all dose levels, the intake of Ba decreased because of reduced water intake, and at termination of the study, the dosage rate was at half of the initial dose. No changes related to Ba ingestion were observed in clinical signs, hematologic parameters, or serum chemistry. The only change noted was a statistically significant decrease in water consumption in the highest-dose group. A slight decrease of adrenal weights in treated animals was noted. The increase in dose, not the increase in duration, produced increased concentrations of tissue Ba; the highest concentration was found in bone. Blood pressure was not measured in this study. A concentration of 50 ppm was identified as a NOAEL for change in water consumption. The National Toxicology Program (NTP 1994) conducted a 13-wk study in which male and female F344/N rats were exposed to BaCl2 dihydrate at 0, 125, 500, 1,000, 2,000, and 4,000 ppm (Ba at 0, 10, 65, 110, and 200 mg/kg/d for males and 0, 10, 35, 65, 115, and 180 mg/kg/d for females). In the highest-dose group, three males and one female died. The cause of death could not be determined. Significant decreases in water consumption were noted in the 4,000 ppm group. Relative and absolute organ-weight changes were also noted in the 2,000 and 4,000 ppm groups. Mild focal and multifocal areas of dilation were seen in the renal proximal tubules of the 4,000 ppm group. In addition to these effects, significant decreases in the magnitude of undifferentiated motor activity were observed in both sexes of rats receiving the 4,000 ppm dose, whereas the decreases were marginal at other doses. No other changes pertaining to neurobehavioral assessments were noted. Also, no changes were seen in cardiovascular measurements such as heart rate, systolic blood pressure, or ECG. The three notable adverse effects in the 13-wk NTP drinking water study are the effects on the renal proximal convoluted tubules (accompanied by significantly increased relative kidney weights), 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) and a NOAEL of 1,000 ppm (Ba at 110-115 mg/kg) were identified. In another subchronic-to-chronic exposure study by Perry et al. (1989), female weanling Long Evans rats (45 g body weight) were pro-

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 mo. The study was not used because of reasons outlined in the 10-d AC section. In the third study, a chronic toxicity study by NTP (1994), both male and female rats were exposed to BaCl2 in their drinking water for 2 y at concentrations of 0, 500, 1,250, and 2,500 ppm (Ba at 0, 15, 30, and 60 mg/kg/d for males and 0, 15, 45, and 75 mg/kg/d for females). Three toxicologically significant observations were noted in this report. Water consumption decreased in a dose-dependent manner; an approximate 23% reduction compared with control values occurred at 2,500 ppm. Evidence of renal injury was noted in female mice: BUN increased, and the kidneys had abnormal pigmentation. Renal nephropathy and crystal formation in the renal tubules were observed in mice that received BaCl2 at 2,500 ppm in the diet for 2 y. The chemical-related renal toxicity was not seen in rats. These effects were used to derive 1,000-d ACs as follows. A dose-related decrease in water consumption was seen as early as 5 wk in the 60 mg/kg/d group. First, a 1,000-d AC was derived based on reduction of water consumption in rats (not in mice). Although at the highest dose (60 mg/kg/d) the decreased water consumption was pronounced, water consumption was also found to be lower in the 30 mg/kg/d group. A NOAEL was identified as 15 mg/kg/d for Ba. A 1,000-d AC for a decrease in water consumption is calculated as follows: 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. The 1,000-d AC for reduction in water consumption is 9 mg/L based on the NTP study (1994). A 1,000-d AC was also calculated using data on the renal toxicity end points (nephropathy and renal crystal formation) from male and female mice after 2 y of exposure to BaCl2 in their drinking water). These data have been summarized in Table 3-7. A summary of the NOAEL and BMDL01 values are shown in Table 3-8.

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 TABLE 3-7 Incidence of Non-Neoplastic Lesions in Kidneys of Mice Exposed to BaCl2 in Drinking Water for 2 Years   Male Mice Female Mice BaCl2 (ppm) Dose (mg/kg/d) Renal Crystals Nephropathy Dose (mg/kg/d) Renal Crystals Nephropathy 0 0 0/50 1/50 0 0/50 0/50 500 30 0/50 0/50 40 0/53 2/53 1,250 75 1/48 2/48 90 0/50 1/50 2,500 160 21/50 19/50 200 36/54 37/54 Source: NTP 1994. TABLE 3-8 Benchmark Dose (BMDL01) and NOAELs for BaCl2-Induced Renal Lesions in Mice Gender Parametera For Renal Crystals (Dose mg/kg/d) For Nephropathy (Dose mg/kg/d) Male BMDL01 40 32 Male NOAEL 75 75 Female BMDL01 75 62 Female NOAEL 90 90 aBMDL01 is defined as the 95% lower confidence limit estimate of a benchmark dose corresponding to an excess risk of 1%. Bench Mark Dose Software version 1.3.2, developed by EPA, was used. Using both the NOAEL and the BMDL01 values listed in Table 3-8, ACs were calculated for both renal toxicity end points as follows: 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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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 Male mice seem to be more susceptible to renal crystal formation as well as nephropathy than the female mice, and the values based on the BMD approach are conservatively lower than the NOAEL method (see Table 3-9). The most conservative of AC values for renal crystals (24 mg/L) and nephropathy (19 mg/L) in male mice, derived using the BMD method, were chosen as the 1,000-d AC. These values are entered in the AC summary table (Table 3-10). TABLE 3-9 Summary of 1,000-d ACs Based on Renal Lesions Species and Sex ACs Based Ona AC for Renal Crystalsb (mg/L) AC for Nephropathyb(mg/L) Mice, male BMDL01 24 19 Mice, male NOAEL 46 45 Mice, female BMDL01 46 37 Mice, female NOAEL 55 54 aThe 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 renal-effects risk and bone-demineralization risks. bThe italicized values represent the most conservative value.

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 TABLE 3-10 Acceptable Concentrations (ACs) for Ba in Drinking Water Toxicity End Points Exposure Species UFs ACs ( mg/ L of water) Reference To NOAELs Species Factor Time Factor Space-flight Factor 1-d 10-d 100-d 1,000 Fluid in the trachea, darkened liver, inflammation of intestine NOAEL = 66 mg/kg; 1 d; gavage Rats, male and female (fasted) 1 10 1 1 165 21 — — Borzelleca et al. 1988 Abnormal ECG LOAEL = 84 mg/kg/d; iv infusion Dogs, male and female 2 10 1 5 21 50 — — Roza and Berman 1971 Reduced water consumption NOAEL = 60 mg/kg; 15-d data Rats, male and female 1 10 1 3 — — — — NTP 1994 Reduced water consumption LOAEL = 45.7 mg/kg; NOAEL = 9.7 mg/kg Rats, 13 wk 1 10 (100/ 91) 3 — 7 7 — Tardiff et al. 1980 Renal (histo-pathologic lesions); thymic and spleen atrophy in male and female mice NOAEL = 65; 13 wk; drinking water Rats, male and female 1 10 (100/ 91) 3 — — 50 — NTP 1994 Neurobehavioral effects (motor activity) NOAEL = 110; 13 wk; drinking water Rats, male and female 1 10 (100/ 91) 1 — — 250 — NTP 1994

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 Neurobehavioral effects ( motor activity) BMDL01 = 32.5 ( BMD method) ; 2 y; BaCl2 in drinking water Rats, female 1 10 1 1 — — 75 — NTP 1994 Reduced water consumption NOAEL = 15; 2 y; drinking water Rats 1 10 1.37a 3 — — — 9 NTP 1994 Renal Crystal formation BMDL01 = 40; 2 y; BaCl2 in drinking water Mice, male 1 10 1.37a 3 — — — 24 NTP 1994 Nephropathy BMDL01 = 32; 2 y; BaCl2 in drinking water Mice, male 1 10 1.37a 3 — — — 19 NTP 1994 SWEGb 21 21 10b 10b aFactor for time extrapolation from 730-d to 1,000-d. bThese values were rounded to 10 for both 100- and 1,000-d ACs.

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists). 1986. Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th Ed. Cincinnati, OH: ACGIH. ATSDR (Agency for Toxic Substances and Disease Registry). 1992. Toxicological Profile for Barium and Compounds. Agency for Toxic Substances and Disease Registry, U.S. Public Health and Service, Washington, DC. Bauer, G.C.H., A. Carlsson, and B. Lindquist. 1956. A comparative study on the metabolism of 140Ba and 45Ca in rats. Biochem. J. 63:535-542. Bauer, G.C.H., A. Carlsson, and B. Lindquist. 1957. Metabolism of 140Ba in man. Acta. Orthop. Scand. 26:241-254. Berman, C.Z., M.G. Jacobs, and A. Bernstein. 1965. Hazards of the barium enema examination as studied by electrocardiographic telemetry. Preliminary report. J. Am. Geriat. Soc. 13: 672-686. Blakeborough, A., M.B. Seridan, and A.H. Chapman. 1977. Complications of barium enema examinations: a survey of UK Consultant Radiologists 1992 to 1994. Clin. Radiol. 52(2):142-148. Bligh, P.H. 1960. Metabolism of barium in rat and man. PhD Thesis, London University. London. Bligh, P.H., and D.M. Taylor. 1963. Comparative studies of the metabolism of strontium and barium in the rat. Biochem. J. 87:612-618. Borzelleca, J.F., L.W. Condie, Jr., and J.L Egle, Jr. 1988. Short-term toxicity (one- and ten-day gavage) of barium chloride in male and female rats. J. Am. Coll. Toxicol. 7:675-685. Brenniman, G.R., and P.S. Levy. 1985. Epidemiological study of barium in Illinois drinking water supplies. Pp. 231-240 in Inorganics in Water and Cardiovascular Disease, E.J. Calabrese, R.W. Tuthill, and L. Condie, eds. Princeton, NJ: Princeton Scientific Publishing. Brenniman, G.R., T. Namekata, W.H. Kojola, B.W. Carnow, and P.S. Levy. 1979. Cardiovascular disease death rates in communities with elevated concentrations of barium in drinking water. Environ. Res. 20:318-324. Brenniman, G.R., W.H. Kojala, P.S. Levy, B.W. Carnow, and T. Namekata. 1981. High barium levels in public drinking water and its association with elevated blood pressure. Arch. Environ. Health 36(1):28-32. Calabrese, E.J. 1977. Excessive barium and radium-226 in Illinois drinking water. J. Environ. Health 39:366-369. Chou, C., and Y.C. Chin. 1943. The absorption, fate, and concentration in serum of barium in acute experimental poisoning. Chin. Med. J. 61:313-322. Clary, J.J., and R.G. Tardiff. 1974. The absorption distribution and excretion of orally administered 133BaC12 in weanling male rats [abstract]. Toxicol. Appl. Pharmacol. 29:139.

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 Cuddihy, R.G., and W.C. Griffith. 1972. A biological model describing tissue distribution and whole-body retention of barium and lanthanum in beagle dogs after inhalation and gavage. Health Phys. 23:621-633. Dallas, C.E., and P.L. Williams. 2001. Barium: rationale for a new oral reference dose. J. Toxicol. Environ. Health B Crit. Rev. 4(4):395-429. Das, N.C., and V. Singh. 1970. Unusual type of cardiac arrest: Case report. Armed Forces Med. J. India 26:344-352. Dencker, L. A. Nilsson, C. Ronnback, and G. Walinder. 1976. Uptake and retention of 133Ba and 140Ba140La in mouse tissues. Acta Radiol. Ther. Phys. Biol. 15(4):273-287. Diengott, D., O Rozsa, N. Levy, S. Muammar. 1964. Hypokalemia in barium poisoning. Lancet 14:343-344. Dietz, D.D., M.R. Elwell, W.E. Davis, and E.F. Meirhenry. 1992. Subchronic toxicity of barium chloride dihydrate administered to rats and mice in the drinking water. Fund. Appl. Toxicol. 19:527-537. Douglass, W.W., and R.P. Rubin. 1964. Stimulant action of barium on the adrenal medulla. Nature 203:305-307. Dourson, M.L. 1994. Methods for establishing oral reference doses (RfDs). Pp. 51-61 in Risk Assessment of Essential Elements, W. Mertz, C.O. Abernathy, and S.S. Olin, eds. Washington, DC: ILSI Press. Durfor, C.N., and E. Becker. 1964. Public water supplies of the 100 largest cities in the United States, 1962. Water-Supply Paper 1812. United States Geological Survey, Washington, DC. Durfor, C.N., and E. Becker. 1968. Public water supplies of the 100 largest cities in the United States. Water-Supply Paper 1812. United States Geological Survey, Washington, DC. Eastwood, G.L. 1972. ECG abnormalities associated with the barium enema. JAMA 219(6):719-721. Edel, J., A. Di Nucci, E. Sabbioni, L. Manzo, M. Tonini, C. Minnoia, and S. Candedoli. 1981. Biliary excretion of barium in the rat. Biol. Trace Elem. Res. 30(3):267-276. Ellestad, M.H. 1999. Ventricular tachycardia during spaceflight. Am. J. Cardiol. 83(8):1300. EPA (U.S. Environmental Protection Agency). 1983. Barium Occurrence in Drinking Water, Food, and Air. Office of Drinking Water, U.S. Environmental Protection Agency, Washington, DC. EPA (U.S. Environmental Protection Agency). 1985. Draft Health Effects Criteria Document for Barium. Office of Drinking Water, U.S. Environmental Protection Agency, Washington, DC. EPA (U.S. Environmental Protection Agency). 1988. Integrated Risk Information System. Barium and Compounds. Minor revisions were made to Oral RfD 1-21-1999. U.S. Environmental Protection Agency, Washington, DC. EPA (U.S. Environmental Protection Agency). 1989. National primary and secondary drinking water regulations. Fed. Regist. 54:22062.

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 EPA (U.S. Environmental Protection Agency). 2002. 2002 Edition of the Drinking Water Standards and Health Advisories. U.S. Environmental Protection Agency, Washington, DC. Erre, N., F. Manca, and A. Parodo. 1980. The short-term retention of barium in man. Health Phys. 38:225-227. Fritsch-Yelle, J.M., U.A. Leuenberger, D.S. D'Aunno, A.C. Rossum, T.E. Brown, M.L. Wood, M.E. Josephson, and A.L. Goldberger. 1998. An episode of ventricular tachycardia during long-duration spaceflight. Am. J. Cardiol. 81(11):1391-1392) Gould, D.B., M.R. Sorrell, and A.D. Lupariello. 1973. Barium sulfide poisoning. Some factors contributing to survival. Arch. Intern. Med. 132:891-894. Hardcastle, J., P.T. Hardcastle, and J.M. Noble. 1985. The secretory action of barium chloride in rat colon. J. Physiol. 361:19-33. Harrison, G.E., T.E.F. Carr, A. Sutton, and J. Rundo. 1966. Plasma concentration and excretion of calcium-47, strontium-85, barium-133 and radium223 following successive intravenous doses to a healthy man. Nature 209(22):526-527. Harrison, G.E., T.E.F. Carr, and A. Sutton. 1967. Distribution of radioactive calcium, strontium, barium and radium following intravenous injection into a healthy man. Int. J. Radiat. Biol. 13:235-247. Hicks, R., L.Q. Caldas, P.R. Dare, P.J. Hewitt. 1986. Cardiotoxic and bronchoconstrictor effects of industrial metal fumes containing barium. Arch. Toxicol. Suppl. 9:416-420. ICPR (International Commission on Radiological Protection). 1973. Alkaline earth metabolism in adult man. ICPR Publication 20. Oxford: Pergamon Press. IRIS (Integrated Risk Information System). 2005. Barium and Compounds (CASRN 7440-39-3). U.S. Environmental Protection Agency. [Online] Available: http://www.epa.gov/iris/subst/0010.htm. [accessed July 11, 2005]. Kanematsu, N., M. Hara, and T. Kada. 1980. Rec assay and mutagenicity studies on metal compounds. Mutat. Res. 77:109-116. Kojola, W.H., G.R. Brenniman, and B.W. Carnow. 1978. A review of environmental characteristics and health effects of barium in public water supplies. Rev. Environ. Health 3:79-95. Kopp, J.F. 1969. The occurrence of trace elements in water. Pp. 59-73 in Proceedings of the Third Annual Conference on Trace Substances in Environmental Health, D.D. Hemphill, ed. Columbia, MO: University of Missouri. Kopp, J.F., and R.C. Kroner. 1967. Trace metals in waters of the United States. A five-year summary of trace metals in rivers and lakes on the United States (Oct 1, 1962-Sept 30, 1967). Federal Water Pollution Control Administration, U.S. Department of Interior, Cincinatti, OH. Kopp, S.J., H.M. Perry, Jr., J.M. Feliksik, M. Erlanger, and E.F. Perry. 1985. Cardiovascular dysfunction and hypersensitivity to sodium pento-barbital

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 induced by chronic barium chloride ingestion. Toxicol. Appl. Pharmacol. 77(2):303-314. Leguay, G., and A. Seigneuric. 1981. Cardiac arrhythmias in space. Role of vagotonia. Acta Astronaut. 8(7):795-801. Lengemann, F.W., R.H. Wasserman, and C.L. Comar. 1959. Studies on the enhancement of radiocalcium and radiostrontium absorption by lactose in the rat. J. Nutr. 68(3):443-456. Lewi, Z., and Y. Bar-Khayim. 1964. Food poisoning from barium carbonate. Lancet 14:342-343. Lisk, D.J., C.A. Bache, and L.A. Essick. 1988. Absorption and excretion of selenium and barium in humans from consumption of Brazil nuts. Nutr. Rep. Int. 38:183-191. McCabe, L.J., J.M. Symons, R.D. Lee, G.G. Robeck. 1970. Survey of community water supply systems. J. Am. Water Works Assoc. 62(11):670-687. McCauley, P.T., and I.S. Washington. 1983. Barium bioavailability as the chloride, sulfate or carbonate salt in the rat. Drug. Chem. Toxicol. 6:209-217. McCauley, P.T., B.H. Douglas, R.D. Laurie, and R.J. Bull. 1985. Investigations into the effect of drinking water barium on rats. Pp.197-210 in Inorganics in Drinking Water and Cardiovascular Disease, E.J. Calabrese, R.W. Tuthill, and L. Condie, eds. Princeton, NJ: Princeton Scientific Publications. Merck Index. 1989. The Merck Index: An encyclopedia of chemicals, drugs, and biologicals, 11th Ed., S. Budavari, M.J. O’Neil, and A. Smith, eds. Rahway, NJ: Merck & Co. Monaco, M., R. Dominici, R. Barisano, and G. Di Palermo. 1991. The evalustion of the presumed mutagenic activity of barium nitrate [in Italian]. Med. Lav. 82(5):439-445. Morton, M.S., P.C. Elwood, and M. Abernathy. 1976. Trace elements in water and congenital malformation of the central nervous system in South Wales. Br. J. Prev. Soc. Med. 30:36-39. Morton, W. 1945. Poisoning by barium carbonate. Lancet 2:738-739. Newton, D., J. Rundo, and G.E. Harrison. 1977. The retention of alkaline earth elements in man, with special reference to barium. Health Phys. 33:45-53. NIOSH (National Institute for Occupational Safety and Health). 1982. Health Hazard Evaluation Report; Sherwin-Williams Company, Coffeyville, Kansas. Report HETA/81-356-1183. National Institute for Occupational Safety and Health, Centers for Disease Control, Cincinatti, OH. Nishioka, H. 1975. Mutagenic activities of metal compounds in bacteria. Mutat. Res. 31:185-190. NRC (National Research Council). 1977. Drinking Water and Health. Washington, DC: National Academy Press. . NRC (National Research Council). 1982. Drinking Water and Health, Vol. 4. Washington, DC: National Academy Press. NTP (National Toxicology Program). 1994. Technical report on the toxicology and carcinogenesis studies of barium chloride dihydrate (CAS No.10326-

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 27-9) in F344/N rats and B6C3FI mice (Drinking Water Studies). NTP TR 432 (NIH Publication No. 94-3163. NTIS Publication No. PB94-214178). National Toxicology Program, U.S. Department of Health and Human Services, Research Triangle Park, NC. Ogen, S., S. Rosenbluth, and A. Eisenberg. 1967. Food poisoning due to barium carbonate in sausage. Israel J. Med. Sci. 3:565-568. Perry, Jr., H.M., E.F. Perry, M.W. Erlanger, and S.J. Kopp. 1985. Barium-induced hypertension. Pp.221-279 in Inorganics in Drinking Water and Cardiovascular Disease, E.J. Calabrese, ed. Princeton, NJ: Princeton Scientific Publications. Perry, Jr., H.M., S.J. Kopp, E.F. Perry, and M.W. Erlanger. 1989. Hypertension and associated cardiovascular abnormalities induced by chronic barium feeding. J. Toxicol. Environ. Health 28(3):373-388. Phelan, D.M., S.R. Hagley, and M.D. Guerin. 1984. Is hypokalemia the cause of paralysis in barium poisoning? Br. Med. J. 289:882. Pierre, L.M., J.R. Schultz, R.L. Sauer, Y.E. Sinyak, V.M. Skuratov, N.N. Pratasov, and L.S. Bobe. 1999. Chemical Analysis of Potable Water and Humidity Condensate: Phase One Final Results and Lessons Learned. SAE Technical Paper Series no. 1999-01-2028. 29th International Conference on Environmental systems, Denver, CO, July 12-15. Roeske, W.R., C. Higgins, J.S. Karliner, R.N. Berk, and R.A. O'Rourke. 1975. Incidence of arrhythmias and ST-segment changes in elderly patients during barium enema studies. Am. Heart J. 90(6):688-694. Rossman, T.G., M. Molina, L. Meyer, P. Boone, C.B Klein, Z. Wang, F. Li, W.C. Lin, and P.L. Kinney. 1991. Performance of 133 compounds in the lambda prophage induction end point of the Microscreen assay and a comparison with S. typhimurium mutagenicity and rodent carcinogenicity assays. Mutat. Res. 260(4):349-367. Roza, O., L.B. Berman. 1971. The pathophysiology of barium: hypokalemic and cardiovascular effects. J. Pharmacol. Exp. Ther. 177(2):433-439. RTECS (Registry of Toxic Effects of Chemical Substances). 1999. Barium chloride, dihydrate (CAS # 103610-37-2). RTECS # CQ8751000. National Institute for Occupational Safety and Health, U.S. Department of Health and Human Services, Cincinnati, OH. Rundo, J. 1967. The retention of barium-133 in man. Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 13(3):301-302 Sax, N.I. 1984. Dangerous Properties of Industrial Chemicals, 6th Ed. New York: Van Nostrand Reinhold Co. Schroeder, H., and M. Mitchener. 1975a. Life-term studies in rats: Effects of aluminum, barium, beryllium and tungsten. J. Nutr. 105:421-427. Schroeder, H., and M. Mitchener. 1975b. Life-term effects of mercury, methyl mercury and nine other trace metals on mice. J. Nutr. 105:452-458. Schroeder, H.A., I.H. Tipton, and A.P. Nason. 1972. Trace metals in man: Strontium and barium. J. Chronic. Dis. 25(9):491-517.

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Spacecraft Water Exposure Guidelines: For Selected Contaminants, Volume 2 Sirover, M.A., and L.A. Loeb. 1976. Infidelity of DNA synthesis in vitro: Screening for potential metal mutagens or carcinogens. Science 194(4272):1434-1436. Sowden, E.M., and S.R. Stitch. 1957. Trace elements in human tissue: 2. Estimation of the concentration of stable strontium and barium in human bone. Biochem. J. 67:104-109. Syed, I.B., and F. Hosain. 1972. Determination of LD50 of barium chloride and allied agents. Toxicol. Appl. Pharm. 22:150-152. Syed, I.B., F. Hosain, and N.S. Mann. 1981. GI tract excretion of barium. Am. J. Protocol. Gastro. 32:16-20. Talwar, K.K., and B.K. Sharma. 1979. Myocardial damage due to barium chloride poisoning. Ind. Heart J. 31:244-245. Tarasenko, N.Y., O.A. Pronin, and A.A. Silayev. 1977. Barium compounds as industrial poisons (an experimental study). J. Hyg. Epidemiol. Microbiol. Immunol. 21(4):361-373. Tardiff, R.G., M. Robinson, and N.S. Ulmer. 1980. Subchronic oral toxicity of BaCl2 in rats. J. Environ. Pathol. Toxicol. 4:267-275. Taylor, D.M., P.H. Bligh, and M.H. Duggan. 1962. The absorption of calcium, strontium, barium and radium from the gastrointestinal tract of the rat. Biochem. J. 83:25-29. Tipton, I.H., P.L. Stewart, and P.G. Martin. 1966. Trace elements in the diet and excreta. Health Phys. 12:1683-1689. Tuovinen, O.H., K.S. Button, and A. Vuorinen. 1980. Bacterial, chemical, and mineralogical characteristics of tubercles in distribution pipelines. J. Am. Water Works Assoc. 72:626-635. Wetherill, S.F., M.J. Guarino, and R.W. Cox. 1981. Acute renal failure associated with barium chloride poisoning. Ann. Intern. Med. 95:187-188. WHO (World Health Organization). 1990. Environmental Health Criteria 107: Barium. Sponsored by United Nations Environment Programme, International Labour Organisation, and World Health Organization, Geneva, Switzerland. Wones, R.G., B.L. Stadler, and L.A. Frohman. 1990. Lack of effect of drinking water barium on cardiovascular risk factor. Environ. Health Perspect. 85:355-359.