Spacecraft Water Exposure Guidelines for Selected Contaminants Volume 3 (2008) / Chapter Skim
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2 Benzene
2 Benzene
Pages 45-85
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From page 45... ...
and John T James, Ph.D., DABT Toxicology Group Habitability and Environmental Factors Division Johnson Space Center National Aeronautics and Space Administration Houston, Texas PHYSICAL AND CHEMICAL PROPERTIES Benzene is a colorless liquid aromatic hydrocarbon.
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From page 46... ...
Benzene is typically not detected in spacecraft water samples. Consumption of benzene in the public water supply is highly unlikely; however, accidental ingestion of water from contaminated streams occurs from leaking gasoline storage tanks, landfills, and other sources (HSDB 2005)
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From page 47... ...
. Absorption of benzene vapor by animals also is rapid, but retention of absorbed benzene might be affected by exposure concentration.
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From page 48... ...
MPO can convert the intermediates to highly reactive and toxic free radical semiquinones and quinones. The remaining benzene oxide can be conjugated with glutathione to produce phenylmercapturic acid, which is excreted in the urine, or it can be converted to benzene glycol (Erexson et al.
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From page 49... ...
. Many minor metabolites are formed in benzene metabolism, of which phenylmercapturic acid and trans,trans-muconic acid are the most important (see Figure 2-2)
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From page 50... ...
Reprinted with permission; copyright 1996, Environmental Health Perspectives. In workers exposed for 7 h to benzene at concentrations of 1 to 76 ppm, the correlation between exposure concentration and urinary phenol excretion was 0.891 (Inoue et al.
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From page 51... ...
. Urinary metabolite data from workers exposed for about 7 h to benzene at 50 ppm suggest that the metabolism of benzene to hydroquinone compounds in humans is quantitatively comparable to that in mice, whereas the metabolism to muconic acid is comparable to that in rats and is one-third that in mice (Henderson et al.
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From page 52... ...
These effects are believed to be caused by benzene rather than by its metabolites, because the onset of CNS effects at extremely high doses is too rapid for metabolism to have occurred. Fatality due to acute benzene exposure has been attributed to asphyxiation, respiratory arrest, CNS depression, and cardiac dysrhythmia.
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From page 53... ...
Hematotoxicity and Immunotoxicity Although benzene-induced hematotoxicity and immunotoxicity are generally associated with prolonged exposure, abnormal hematologic parameters have been observed in some workers exposed to low concentrations for short periods (ATSDR 1989)
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From page 54... ...
Positive results were obtained in studies of DNA binding in rabbit bone marrow and rat liver mitoblasts; negative results were obtained in studies of DNA breaks in rat hepatocytes, Chinese hamster V79 cells, and mouse L5178Y cells; and mixed results were obtained in studies of chromosomal aberrations and sister chromatid exchange (SCE) in human lymphocytes (ATSDR 1989)
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From page 55... ...
. Workers exposed even to low concentrations (e.g., 50 ppm)
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. Of 32 cases of aplastic anemia among workers exposed to benzene at 150 to 650 ppm for 4 mo to 15 y, there were eight deaths due to thrombocytopenic hemorrhage and infection (Aksoy et al.
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From page 57... ...
. Bone marrow cellularity and pluripotential stem cells were significantly reduced in C57BL mice exposed for 2 wk at 100 ppm, but not at 10 or 25 ppm (Cronkite et al.
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From page 58... ...
. Numerous studies have shown that benzene-induced bone marrow depression is the result of inhibitory effects on proliferation, maturation, or replication of pluripotential stem cells or early proliferating committed cells in the erythroid or myeloid lines (ATSDR 1989)
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From page 59... ...
along with 18 other hydrocarbons. Expected benzene exposure concentrations were distinguished based on the work task.
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An association was reported between total counts of WBCs, granulocytes, lymphocytes, B cells, and platelets (hematotoxicity) and the cohort's benzene exposure that occurred in the preceding month.
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and adsorbed tetanus toxoid was observed in Swiss albino mice exposed at 200 ppm for 6 h/d for 10 to 20 d but was not observed at 50 ppm (Stoner et al.
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. In rotogravure workers exposed at 125 to 532 ppm for
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. Even at low benzene concentrations, the number of chromosomal aberrations increased; for example, increases were found in 52 workers exposed to benzene at <10 ppm (estimated time-weighted average exposure 2.1 ppm)
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From page 64... ...
. A mortality study and continued follow-up studies of rubber-industry workers exposed at 10 to 100 ppm for 10 y or more reported excessive mortality from myelogenous leukemia and reported a direct correlation between benzene exposure and other forms of leukemia (Infante et al.
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In later studies by the same laboratory, myelogenous leukemia occurred in 1 of 40 CD-1 mice exposed at 100 ppm and in 2 of 40 exposed at 300 ppm for 6 h/d, 5 d/wk for life (Goldstein et al.
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, with the resultant appearance of preleukemic and leukemogenic clones from stem cells exposed to leukemogenic agents before benzene exposure (Harigaya et al.
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. In another study, an increased frequency of chromatid and isochromatid breaks and SCE was found in lymphocytes from 14 children of female workers exposed to benzene during pregnancy; however, the workers were also exposed to other organic solvents (FunesCravioto et al.
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. No pregnancies were reported in 10 female rats exposed to benzene at 210 ppm for 10 to 15 d and then joined by two unexposed males (Gofmekler 1968)
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In Tables 2-3 and 2-4, acceptable concentrations (AC) for spacecraft water exposure guidelines (SWEGs)
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. They noted in their rationale for setting benzene SMAC values that the immediate effects of benzene exposure
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From page 71... ...
Analyses of urinary metabolites indicated that both humans and mice have a greater propensity to metabolize benzene to its toxic metabolites -- muconic acid and hydroquinone -- than do rats, monkeys, and chimpanzees. The ratios of hydroquinone and muconic acid to phenol in the urine of mice were 80% and 300%, respectively, compared with concentrations in human urine (Henderson et al.
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From page 72... ...
= 21 mg/d. Applying a factor for absorption from the gastrointestinal tract, which is more relevant to the ingestion of benzene via drinking water, the total dose per day will be adjusted as follows: 10-d acceptable amount per day via oral ingestion = 21 mg/d(total inhalation, 7-d SMAC)
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From page 73... ...
= 1.2 mg/d. Assuming a nominal volume of water for ingestion as 2.8 L/d, which the Johnson Space Center Toxicology Group has used in deriving SWEGs for various compounds, the AC per liter of water for 100 d can be derived as follows: 100-d AC = [1.2 mg/d(100-d acceptable amount, oral ingestion)
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From page 74... ...
= 1.2 mg/d. Assuming a nominal volume of water for ingestion as 2.8 L/d, which the Johnson Space Center Toxicology Group has used in deriving SWEGs for various compounds, the AC per liter of water for 1,000 d can be derived as follows: 1,000-d AC = [1.2 mg/d(1,000-d acceptable amount, oral ingestion)
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1974. Leukemia in shoe-workers exposed chroni cally to benzene.
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1986. An update of mortality among chemical workers exposed to benzene.
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1971a. Chromosome studies in workers exposed to benzene or toluene or both.
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1981b. Acute and chronic dose/response effect of benzene inhalation on the peripheral blood, bone marrow, and spleen cells of CD-1 male mice.
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2004. Hematotoxicity in workers exposed to low levels of benzene.
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1972. Reproductive power and the incidence of gynecological disorders in female workers exposed to the combined effect of benzene and chlorinated hydrocarbons [in Russian]
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2000. Guidelines for Developing Spacecraft Water Exposure Guidelines for Space Station Contaminants.
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1984. A cytogenetic study on workers exposed to low concentra tions of benzene.
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1981. Protracted benzene exposure causes a proliferation of myeloblasts and/or promye locytes in CD-1 mice.
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1980. Cytogenetic effects of inhaled benzene in murine bone marrow: Induction of sister chromatid exchanges, chromosomal aber rations and cellular proliferation inhibition in DBA/2 mice.
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1967. Fatal benzene exposure by glue sniff ing.
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