TOXICOLOGICAL PROFILE FOR BARIUM AND COMPOUNDS ...

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44 2. HEALTH EFFECTS designed to test the effect of barium chloride on sporulation frequency, recombination frequency, and meiotic failures in Saccharomyces cerevisiae demonstrated a definite inhibition of sporulation. Effects on recombination frequency and meiotic failures were ambiguous. Barium chloride may have caused a marginal increase in recombination frequencv and information of diploid clones (Sora et al. 1986), but the data are inconclusive. The data available to date are insufficient to support a conclusive statement regarding the genotoxicity of barium and barium compounds. Cancer. No adequate human studies were available that evaluated the carcinogenic potential of barium. Two chronic oral studies were available that examined the incidence of tumors in rats and mice exposed to barium acetate in drinking water for lifetime (Schroeder and Mitchener 1975a, 1975b). Although results of these oral studies were negative for carcinogenicity, they were inadequate for evaluating carcinogenic effects because insufficient numbers of animals were used, it was not determined whether or not a maximum tolerated dose was achieved, a complete histological examination was not performed, and only one exposure dose was evaluated. Precancerous lesions (dysplasia) were reported in one study in which a woman was treated on the cervix with a barium chloride solution; however, the relevance of this limited observation cannot be determined because only one subject was treated and because the vehicle solution was not specified (Ayre 1966). Results of one skin-painting study with mice suggest that barium hydroxide extract derived from tobacco leaf acted as a tumor-promoting agent; however, it cannot be determined whether or not this apparent positive tumorigenic response was due to barium hydroxide or some other component of the tobacco leaf extract (Van Duuren et al. 1968). Barium has not been evaluated by EPA for human carcinogenic potential (IRIS 1991). 2.5 BIOMARKERS OF EXPOSURE <strong>AND</strong> EFFECT Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 1989). A biomarker of exposure is a xenobiotic substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in readily obtainable body fluid(s) or excreta. However, several factors can confound the use and interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures from more than one source. The substance being measured may be a metabolite of another xenobiotic substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental conditions (e.g., duration and route of
45 2. HEALTH EFFECTS exposure), the substance and all of its metabolites may have left the body by the time biologic samples can be taken. It may be difficult to identify individuals exposed to hazardous substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as copper, zinc, and selenium). Biomarkers of exposure to barium are discussed in Section 2.5.1. Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an organism that, depending on magnitude, can be recognized as an established or potential health impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung capacity. Note that these markers are often not substance specific. They also may not be directly adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused by barium are discussed in Section 2.5.2. A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or other characteristic or a preexisting disease that results in an increase in absorbed dose, biologically effective dose, or target tissue response. If biomarkers of susceptibility exist, they are discussed in Section 2.7, "POPULATIONS THAT ARE UN-USUALLY SUSCEPTIBLE." At present, there are no‘well-established biomarkers of exposure and effect for barium. Data suggesting possible biomarkers are presented below. 2.5.1 Biomarkers Used to Identify and/or Quantify Exposure to Barium Barium can be measured in bone, blood, urine, and feces. It has been shown to be sequestered in bone and teeth and excreted in feces and urine. Background levels of barium in bone are approximately 2 µg/g wet weight (ICRP 1974; Scroeder et al. 1972). Background levels of barium in blood, urine, and feces will vary with daily intake of barium. However, the following levels have been reported: bone, 2 ppm (ICRP 1974; Scroeder et al. 1972); feces, 690-1,215 µg/day (ICRP 1974; Scroeder et al. 1972; Tipton et al, 1969); and urine, 17-50 µg/day (ICRP 1974; Scroeder et al. 1972; Tipton et al. 1969). There are no data correlating bone, blood, urine, or feces levels of barium with specific exposure levels. For more detailed information on the toxicokinetics of barium, see Section 2.3. Hypokalemia and hypertension are effects usually found in cases of acute and intermediate exposures to relatively high doses of barium. While it is reasonable to expect the dose level to influence the presence of these effects, there are no data supporting a correlation between dose level and
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TOXICOLOGICAL PROFILE FOR BARIUM AN
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iii FOREWORD The Superfund Amendmen
Page 14 and 15: 2 1. PUBLIC HEALTH STATEMENT chlori
Page 16 and 17: 4 1. PUBLIC HEALTH STATEMENT irrita
Page 19 and 20: 7 2. HEALTH EFFECTS 2.1 INTRODUCTIO
Page 21 and 22: 9 2. HEALTH EFFECTS from any of the
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Page 34 and 35: 22 2. HEALTH EFFECTS either 0.071,
Page 36 and 37: 24 2. HEALTH EFFECTS plasma fibrino
Page 38 and 39: 26 2. HEALTH EFFECTS rats and mice
Page 40 and 41: 28 2. HEALTH EFFECTS barium/kg/day
Page 42 and 43: 30 2. HEALTH EFFECTS purulent disch
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Page 46 and 47: 34 2. HEALTH EFFECTS Animal studies
Page 48 and 49: 36 2. HEALTH EFFECTS may potentiall
Page 50 and 51: 38 2. HEALTH EFFECTS sulfate enema
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Page 67 and 68: 55 2. HEALTH EFFECTS Developmental
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Page 71: 59 3. CHEMICAL AND PHYSICAL INFORMA
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Page 85: 73 5. POTENTIAL FOR HUMAN EXPOSURE
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97 6. ANALYTICAL METHODS However, i
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105 8. REFERENCES ACGIH. 1982. TLVs
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107 8. REFERENCES *Boothe PN. James
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109 8. REFERENCES Clary JJ, Tardiff
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111 8. REFERENCES Douglas WW, Rubin
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113 8. REFERENCES *EPA. 1984. Healt
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115 8. REFERENCES *FSTRhC. 1988. Fe
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117 8. REFERENCES *Hem JD. 1959. St
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119 8. REFERENCES Kolpakov W. 1971.
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121 8. REFERENCES *McCauley PT, Dou
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123 8. REFERENCES NIOSH. 1987a. NIO
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125 8. REFERENCES *Pierce FD, Brown
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127 8. REFERENCES *Sax NI, Lewis RJ
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129 8. REFERENCES Simmonds RJ, Jame
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131 8. REFERENCES Syed IB, Hosain F
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133 8. REFERENCES Weiss G, ed. 1986
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136 9. GLOSSARY Immediately Dangero
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138 9. GLOSSARY Short-Term Exposure
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A-2 APPENDIX A three LSE tables and
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A-4 APPENDIX A (18). Estimated Uppe
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A-8 APPENDIX A MRL users should be
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