Spacecraft Water Exposure Guidelines for Selected Contaminants Volume 2 (2007) / Chapter Skim
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Appendix 1 Acetone
Appendix 1 Acetone
Pages 9-38
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Appendixes
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1975) on acetone suggest that normal blood acetone concentrations in women (1.8-4.2 mg% = 18-42 μg/dL)
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TOXICOKINETICS AND METABOLISM Much of the data in the literature regarding acetone toxicokinetics and metabolism involves exposure by inhalation, but because of the general distribution of acetone in body water and its relatively slow metabolism, as described below, the data should hold true for acetone exposures by ingestion as well. Absorption Acetone is rapidly and almost totally absorbed from the stomach and is also absorbed by inhalation, by mucous membranes, and, to some
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. The amount of radioactivity in tissues increased as the exposure time increased from 1 to 6 h but increased only slightly or not at all in all tissues except adipose tissue at exposure times greater than 6 h (12 h, 24 h, and 5 d)
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. In a 10-d study of female rats, tolerance was reported to develop whereby the effects of inhaled acetone on the inhibition of avoidance behavior and escape response in rats became weaker upon repeated administration (Goldberg et al.
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On a milligram per kilogram basis, Haggard et al.'s (1944) estimate of the metabolic rate of acetone in rats implies that dose rates exceeding about 11 g/d in humans could lead to an accumulation of acetone in a 70kg person.
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Human Lethargy, minimal responsiveness; blood acetone Ramu et al. 1978 acetone; presumed concentration = 0.25 g/dL; pharynx was not red or ingestion by an swollen, nor were there erosions of the soft palate; alcoholic woman recovery was gradual over 3-4 d; acetone half-life = 31 h Estimated 6 oz of nail Bolus Human (30 mo Sedated and nonresponsive; no reflexes; Gamis and polish remover (65% old)
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1991; water male and fe- NOAEL for bone marrow hypoplasia in males; NTP 1991 Rats male; B6C3F1 LOAEL for decreased water consumption in rats male: 4.3 g/kg/d mice, male and and mice; LOAEL for decreased weight gain in female: 4.4 g/kg/d female rats; increased kidney weights in rats Mice male: 6.3 g/kg/d female: 8.8 g/kg/d 20,000 ppm in drinking 14 d F344/N rats, LOAEL for increased relative kidney weight in Dietz et al. 1991; water male and female female rats; LOAEL for increased relative liver NTP 1991 male: 2.6 g/kg/d weight in male and female rats female: 2.3 g/kg/d 20,000 ppm in drinking 14 d B6C3F1 mice, LOAEL for liver hypertrophy in male mice and Dietz et al.
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male and female male rats; LOAEL for mild spermatogenic toxicity NTP 1991 and increased relative weight of testis; LOAEL for mild leukocytosis in females; decreased water consumption, but no dehydration; mild macrocytic normochromic anemia in male rats; LOAEL for decreased body weight in rats; LOAEL for decreased water consumption in rats 50,000 ppm in drinking 13 wk B6C3F1 mice, LOAEL for increased liver and decreased spleen Dietz et al. 1991; water (11 g/kg/d)
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male and female concentrations in males; LOAEL for increased NTP 1991 relative weight of liver in males and females; LOAEL for increased relative weight of kidney in females; LOAEL for increased severity of nephropathy in males; LOAEL for minimal-to mild splenic hemosiderosis in males; LOAEL for mild leukocytosis in males 20,000 ppm in drinking 13 wk B6C3F1 mice, NOAEL for increased liver weight in female mice Dietz et al. 1991; water (5.9 g/kg/d)
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. Hepatotoxicity Acetone induces hepatocellular hypertrophy and dose-related increases in liver weight.
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Bone marrow hypoplasia was reported in five of five male, but no female rats exposed to acetone in their drinking water for 14 d at 100,000 ppm (6,942 mg/kg/d) (Dietz et al.
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. Female rats were trained according to an avoidance-escape paradigm.
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Subchronic and Chronic Toxicity NTP conducted 2-wk and 13-wk toxicity studies in rats and mice receiving acetone in drinking water at concentrations of 0, 5,000, 10,000, 20,000, 50,000, and 100,000 ppm for 2 wk and 0, 1,250 (male mice only) , 2,500, 5,000, 10,000, 20,000, and 50,000 (rats and female mice only)
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. Significantly increased relative kidney weights were seen in female rats exposed to acetone for 13 wk to 20,000 or 50,000 ppm, but in male rats, such increases were significant only at 50,000 ppm.
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In another study, increased hemoglobin, hematocrit, and mean cell volume were seen in male but not female rats treated by gavage at 2,500 mg/kg/d for 46 d, and in both males and females at this dose for 13 wk (American Biogenics Corp.
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Acetone concentrations of 50,000 ppm produced a statistically significant increased incidence of abnormal sperm (NTP 1991)
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ATSDR's MRL Calculations and Rationale The intermediate duration MRL was based on a NOAEL value of 200 mg/kg/d (2,500 ppm in drinking water) for macrocytic anemia in rats in the 13-wk drinking water study (see Table 1-3)
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can be set for the following adverse effects of acetone exposure discussed above: hematologic toxicity (bone marrow hypoplasia and macrocytic anemia) and splenic hemosid TABLE 1-3 Exposure Limits Set by Other Organizations Exposure Limit Equivalent Drinking Water Concentration (mg/L)
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NOAEL for bone marrow hypoplasia in male rats after 14 d of exposure (Dietz et al.
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UFs ACs (mg/L) Exposure Species and Inter- To Inter- Exposure Space- 1,000 End Point Data Reference individual NOAEL species Time flight 1d 10 d 100 d d NOAEL for 4,312 Rat, male 1 1 10 1 3 3,500 3,500 -- -- bone marrow mg/kg/d (NTP 1991)
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. 100-d ACs Mild macrocytic anemia was reported in male rats receiving acetone for 13 wk at doses above 200 mg/kg/d (acetone concentrations >2,500 ppm)
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For macrocytic anemia, the AC is calculated as follows: 1,000-d ACs = 0.1 × 100-d ACs = 0.1 × 150 mg/L = 15 mg/L. For mild nephropathy and splenic hemosiderin, 1,000-d ACs = 0.1 × 100-d ACs = 0.1 × 2,000 mg/L = 200 mg/L.
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Of the effects induced by exposure to acetone, only bone marrow hypoplasia and macrocytic anemia could potentially be exacerbated by known effects of launch, microgravity, or re-entry. Because the mechanisms involved in the control of space anemia are not well known enough to rule out the possibility of additive or synergistic effects with bone marrow hypoplasia and macrocytic anemia caused by acetone exposures, a spaceflight factor of 3 was used to adjust the ACs.
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1988. Effects of short duration exposures to acetone and methyl ethyl ketone.
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1979a. Effects of acetone, methyl ethyl ketone and methyl isobutyl ketone on a match-to-sample task in the baboon.
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1977. Hepatorenal lesions after acute acetone intoxication.
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1973. Acute acetone intoxication involving eight male workers.
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38 Spacecraft Water Exposure Guidelines Zettinig, G., N Watzinger, B
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