National Academies Press: OpenBook
« Previous: Introduction
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

Appendixes

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

This page intentionally left blank.

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

1
Acetone

Hector D. Garcia, Ph.D. NASA-Johnson Space Center Toxicology Group Habitability and Environmental Factors Branch Houston, Texas

PHYSICAL AND CHEMICAL PROPERTIES

Acetone is a clear, colorless, highly volatile, flammable liquid with a sweet, fruity aroma (odor threshold = 13 parts per million [ppm]) and excellent solvent properties. It forms explosive mixtures with air or oxygen (see Table 1-1).

OCCURRENCE AND USE

Acetone is a product of normal metabolism in humans and animals. It is produced during the breakdown of fat and is used in the synthesis of glucose and fat. Trace amounts are detectable in normal human blood (7.0-14.0 micromoles per liter [µmol/L] = 0.4-0.8 micrograms per milliliter [µg/mL]) and urine (4.0-35.0 µmol/L = 0.2-2.0 µg/mL) (Rowe and Wolf 1963; Wang et al. 1994; de Oliveira and Pereira Bastos de Siqueira 2004). Endogenous concentrations of acetone in the blood have been reported up to 10 µg/mL, and concentrations during diabetic ketoacidosis have ranged from 100 to 700 µg/mL (Gamis and Wasserman 1988). Data from a National Institute for Occupational Safety and Health (NIOSH) report (Stewart et al. 1975) on acetone suggest that normal blood acetone concentrations in women (1.8-4.2 mg% = 18-42 µg/dL) may be two to three times higher than in men (0.5-1.4 mg% = 5-14 µg/mL), but no other reports could be found to confirm this. High acetone concentrations in serum and breath are often indicative of altered metabolic states including diabetes, vitamin E deficiency, and fasting (NTP 1991).

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

TABLE 1-1 Physical and Chemical Properties of Acetonea

Formula

C3H6O

 

Chemical Name

Acetone

Synonyms

Propanone, 2-propanone, dimethylketone, dimethyl formaldehyde, dimethylketal, ketone propane, beta-ketopropane, methyl ketone, pyroacetic acid, pyroacetic ether

CAS registry no

67641

Molecular weight

58.09

Boiling point

56.48°C

Melting point

−94.6°C

Density

0.7972 g/cc (at 15°C)

Vapor Pressure

400 mm at 39.5°C, 200 mm at 25°C

Vapor density

2 (air = 1)

Solubility

Infinitely soluble in water; miscible with alcohol, dimethylformamide, chloroform, most oils, and ether

Lower Explosive Limit

2% (in air)

Upper explosive Limit

13% (in air)

Odor Threshold (in air)

13 ppm; 47 mg/m3

Odor Threshold (in water)

20 ppm; 20 mg/L

aData from HSDB 2006.

Acetone is not routinely used in spacecraft during flight but may be part of in-flight scientific experiments. Acetone is found in the spacecraft atmosphere on almost every mission at concentrations up to 8 ppm in Skylab (Liebich et al. 1975) and up to 1.2 ppm during shorter Shuttle missions—probably from crew metabolism and offgassing.

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

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

degree, through the skin. The rate of absorption of ingested acetone depends on the amount of food in the stomach. In one subject, peak blood levels of acetone were seen 10 min after ingestion of acetone on an empty stomach, while acetone ingested about 10 min after a meal was more slowly absorbed, with lower peak levels achieved at 48-59 min after ingestion (Widmark 1919).

Distribution

No studies were found on the distribution of acetone after ingestion.

In studies of the inhalation toxicokinetics of acetone in rats, Hallier et al. (1981) found that acetone is mainly, but not exclusively, distributed within the body water compartment under conditions of negligible metabolism (saturation of metabolizing enzymes). The kinetics of the exhalation of acetone was strictly monoexponential, indicating that it does not distribute into a “deep compartment”—that is, one from which it is released only slowly. Also, acetone is water soluble and will not accumulate in adipose tissue.

Mice exposed to 2-[14C]-acetone vapor (500 ppm) for periods of 1 h to 5 days (d) were examined for the tissue distribution of radioactivity (Löf et al. 1980; Wigaeus et al. 1982). 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) (Wigaeus et al. 1982). Liver and pancreas showed the highest concentration of radioactivity; the lowest concentrations were in muscles and white adipose tissue. After 3 or 5 d of inhalation exposure (6 h/d) to 500 ppm 2-[14C]-acetone vapor, the radioactive concentration in mouse tissues was highest in brown adipose tissue, followed by liver and pancreas (Wigaeus et al. 1982). Only about 10% of the radioactivity in the liver was unchanged acetone.

Metabolism

Ramu et al. (1978) in a case report involving the ingestion of nail polish remover by an alcoholic estimated that humans can metabolize acetone at a rate probably not exceeding 1 g/h, but none of the metabolites were identified. On a gram per kilogram basis, the rate of acetone metabolism in humans has been reported to be about half that the rat

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

(Haggard et al. 1944), with metabolism being nonlinear and saturable. Haggard et al. documented a zero-order elimination rate in rats of 13 milligrams per kilograms per hour (mg/kg/h) at a blood acetone concentration of 0.2 g/deciliter (dL). 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. 1964), probably because of an induction of metabolic enzymes in the liver.

Several studies in rats have shown that acetone can be metabolized by three separate gluconeogenic pathways, with the first step in all cases being the hydroxylation of one of the methyl groups by acetone monooxygenase to form acetol (NTP 1991). One of the intermediates in the metabolism of acetone to carbon dioxide is formate, which in humans, is metabolized more slowly than in rodents.

Elimination

The main route of excretion of acetone is via the lungs—regardless of the route of exposure—with very little excreted in the urine (Ramu et al. 1978; Wigaeus et al. 1981; Gamis and Wasserman 1988). About half of the acetone is exhaled unchanged in humans, and the other half is exhaled as carbon dioxide produced from the metabolism of acetone (Wigaeus et al. 1982). Several different estimates of the half-life of acetone in blood have been reported, with the reported half-life increasing with the dose of acetone (DiVincenzo et al. 1973; Ramu et al. 1978; Wigaeus et al. 1981; Gamis and Wasserman 1988). In acute intoxications in adult humans, the half-life of acetone in plasma has been estimated at approximately 31 h and is consistent with a first-order elimination process (Ramu et al. 1978). A more recent estimate of the elimination plasma half-life of acetone in humans is 18 h (Sakata et al. 1989). Jones reported half-lives for acetone in the blood and urine ranging from 3-27 h, but some of the measurements were from ingestion of isopropanol or denatured alcohol rather than acetone itself (Jones 2000). A half-life of only 3.9 h was estimated for volunteers inhaling acetone at 250 ppm for 4-h and assuming first-order kinetics (Dick et al. 1988). A case report of a 42-year-old man who intentionally swallowed 800 mL of acetone reported acetone concentrations of 2,000 mg/L in serum and 2,300 mg/L in urine and an elimination half-life of 11 h with sequelae-free survival after aggressive treatments including multiple gastric lavages, hyperventilation, hemofiltration, forced diuresis and hydration (Zettinig et al.

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

1997). Two studies on inhaled acetone (Matsushita et al. 1969b and Di-Vincenzo et al. 1973, as cited in OSHA 1989) suggest that chronic intermittent exposure to high enough doses of acetone on a daily basis can lead to the bioaccumulation of acetone. Based on Ramu et al.’s (1978) estimate of the maximum metabolism rate in humans (1 g/h), accumulation in the blood should be seen for dose rates exceeding about 24 g/d. 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 70-kg person.

TOXICITY SUMMARY

Systemic effects reported in humans and animals after oral or inhalation exposure to acetone are described below and in Table 1-2.

At high doses, whether by inhalation or ingestion, manifestations of acute acetone toxicity in humans primarily involve central nervous system (CNS) depression that ranges from lethargy, slurred speech, and ataxia to stupor, coma, and respiratory depression (Ross 1973; Ramu et al. 1978; Gamis and Wasserman 1988). Other adverse effects of high doses include vomiting, hematemesis, excessive thirst, polyuria, hyperglycemia, and occasionally, metabolic acidosis (probably because of the metabolism of acetone to formate) (Ross 1973; Ramu et al. 1978; Gamis and Wasserman 1988). One Soviet investigator reported that four individuals acutely exposed (one by inhalation and three orally) to unspecified concentrations and amounts of acetone developed liver lesions and, in two of the orally intoxicated individuals, mild renal lesions (Mirchev 1977). The quality of this case study report was not evaluated, because it was written in Bulgarian with only the abstract translated into English; thus, it could not be determined if the four patients had also been exposed to other agents such as alcohol or may have had pre-existing lesions of the liver or kidneys.

Acute and Short-Term Exposures
General

Humans who ingest up to 20 mL of acetone do not show any adverse effects (Gosselin et al. 1984). Ingestion of 200 mL, however, can

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

TABLE 1-2 Toxicity Summary

 

 

Concentration

Exposure Duration

Species

Effects

Reference

Effects in Humans

 

 

~200 mL pure acetone (~2,241 mg/kg)

Bolus

Human

Deep coma; red and swollen throat and erosion in soft palate and entrance to esophagus; disturbance of gait 6 d after ingestion; diabetes-like condition 4 wk after ingestion with hyperglycemia, polyuria, and excessive thirst

Gitelson et al. 1966

Unknown amount of acetone; presumed ingestion by an alcoholic woman

1 wk?

Human

Lethargy, minimal responsiveness; blood acetone concentration = 0.25 g/dL; pharynx was not red or swollen, nor were there erosions of the soft palate; recovery was gradual over 3-4 d; acetone half-life = 31 h

Ramu et al. 1978

Estimated 6 oz of nail polish remover (65% acetone, 10% isopropanol)

Bolus

Human (30 mo old)

Sedated and nonresponsive; no reflexes; generalized tonic-clonic seizure; serum acetone concentration = 445 mg/dL; gradual recovery over 4 d with no adverse sequelae; acetone half-life = 19 h initially, then 13 h in the later stages of recovery

Gamis and Wasserman 1988

>12,000 ppm in air in a pit

2 min-4 hr

Human (n = 8)

Throat and eye irritation, leg weakness, chest tightness, headache, dizziness, confusion, unconsciousness, vomiting; gradual, dose-dependent recovery

Ross 1973

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

Effects in Animals

 

 

 

 

100,000 ppm in drinking water

14 d

F344/N rats, male and female; B6C3F1 mice, male and female

LOAEL for bone marrow hypoplasia in male rats; LOAEL for emaciated appearance in rats; LOAEL for decreased weight gain in male mice; decreased water consumption and weight gain in rats and male mice; liver hypertrophy in male and female mice

Dietz et al. 1991; NTP 1991

Rats

 

male: 6.9 g/kg/d

 

female: 8.6 g/kg/d

 

Mice

 

 

male: 10.3 g/kg/d

 

 

female: 12.7 g/kg/d

 

 

50,000 ppm in drinking water

14 d

F344/N rats, male and female; B6C3F1 mice, male and female

LOAEL for liver hypertrophy in female mice; NOAEL for bone marrow hypoplasia in males; LOAEL for decreased water consumption in rats and mice; LOAEL for decreased weight gain in rats; increased kidney weights in rats

Dietz et al. 1991; NTP 1991

Rats

 

male: 4.3 g/kg/d

 

female: 4.4 g/kg/d

 

Mice

 

 

male: 6.3 g/kg/d

 

 

female: 8.8 g/kg/d

 

 

20,000 ppm in drinking water

14 d

F344/N rats, male and female

LOAEL for increased relative kidney weight in female rats; LOAEL for increased relative liver weight in male and female rats

Dietz et al. 1991; NTP 1991

male: 2.6 g/kg/d

 

female: 2.3 g/kg/d

 

20,000 ppm in drinking water (3.9-5.5 g/kg/d)

14 d

B6C3F1 mice, male and female

LOAEL for liver hypertrophy in male mice and NOAEL for liver hypertrophy in female mice

Dietz et al. 1991; NTP 1991

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

Concentration

Exposure Duration

Species

Effects

Reference

10,000 ppm in drinking water

14 d

F344/N rats, male and female; B6C3F1 mice, male and female

NOAEL for liver hypertrophy

Dietz et al. 1991; NTP 1991

Rats

 

male: 1.6 g/kg/d

 

female: 1.5 g/kg/d

 

Mice

 

 

male: 1.6 g/kg/d

 

 

female: 3.0 g/kg/d

 

 

5,000 ppm in drinking water

14 d

B6C3F1 mice, male and female

LOAEL for increased liver weight

Dietz et al. 1991; NTP 1991

Mice

 

male: 1.0 g/kg/d

 

female: 1.6 g/kg/d

 

50,000 ppm in drinking water (3.1-3.4 g/kg/d)

13 wk

F344/N rats, male and female

LOAEL for increased relative kidney weight in male rats; LOAEL for mild spermatogenic toxicity 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

Dietz et al. 1991; NTP 1991

50,000 ppm in drinking water (11 g/kg/d)

13 wk

B6C3F1 mice, female

LOAEL for increased liver and decreased spleen weights in female mice; increased kidney weights; LOAEL for decreased water consumption in mice

Dietz et al. 1991; NTP 1991

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

20,000 ppm in drinking water (1.6-1.7 g/kg/d)

13 wk

F344/N rats, male and female

Decreased erythrocyte counts and hemoglobin concentrations in males; LOAEL for increased 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

Dietz et al. 1991; NTP 1991

20,000 ppm in drinking water (5.9 g/kg/d)

13 wk

B6C3F1 mice, female

NOAEL for increased liver weight in female mice

Dietz et al. 1991; NTP 1991

10,000 ppm in drinking water (0.9 g/kg/d)

13 wk

F344/N rats, male

NOAEL for mild nephropathy and splenic hemosiderin deposits

Dietz et al. 1991; NTP 1991

5,000 ppm in drinking water (0.4 g/kg/d)

13 wk

F344/N rats, male

LOAEL for decreased reticulocyte counts (macrocytic anemia?)

Dietz et al. 1991; NTP 1991

5,000 ppm in drinking water (1.4 g/kg/d)

13 wk

B6C3F1 mice, male

LOAEL for increased liver weight in males

Dietz et al. 1991; NTP 1991

2,500 ppm in drinking water (0.2 g/kg/d)

13 wk

F344/N rats, male

LOAEL for marginally increased mean corpuscular hemoglobin and mean cell volume (indicative of folate deficiency?), with no change in mean corpuscular hemoglobin concentration (indicative of mild macrocytic normochromic anemia); these effects were not seen in female rats at concentrations below 50,000 ppm

Dietz et al. 1991; NTP 1991

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

result in hyperglycemia, restlessness, throat irritation, vomiting that progresses to hematemesis, and progressive nervous system depression as indicated by stupor and shallow respiration (Krasavage et al. 1982; ACGIH 1986; Arena and Drew 1986). The toxic range of acetone has been estimated to be 200-300 µg/mL in blood, with lethal concentrations estimated to be greater than 550 µg/mL (Gamis and Wasserman 1988). Intoxication was not observed, however, in volunteers with blood concentrations up to 33 µg/mL, exposed by either ingestion or inhalation (Gamis and Wasserman 1988). The highest blood concentrations of acetone reported (445 µg/mL) produced stupor, respiratory depression, and convulsions in a 30-month (mo)-old boy who ingested about 8 ounces (oz) (26 mL/kg) of finger nail polish remover composed 65% of acetone, 10% of isopropanol, and 25% not reported. The anesthetic potency of acetone is greater than that of ethanol at equivalent blood concentrations (Gosselin et al. 1984). No permanent toxic sequelae have been reported (Gamis and Wasserman 1988).

Inhalation of acetone at >1,000 ppm produces effects on the CNS, gastrointestinal tract, and kidneys in animals and humans. The following signs have been reported: CNS depression indicated by an initial stimulatory and excitatory restlessness phase followed by euphoria and hallucinations, narcosis, anesthesia, dyspnea, headache, vertigo, general muscular weakness including dysarthria and ataxia, and coma; nausea, vomiting, inflammation, and hematemesis; albuminuria, hematuria, and leukocyturia; and hyperglycemia and increases in bilirubin and urine urobilin (Rowe and Wolf 1963; Mirchev 1977; Nelson and Webb 1978; Geller et al. 1979a,b; Baselt 1982; Krasavage et al. 1982; Finkel 1983; Inoue 1983; Windholz 1983; ACGIH 1986; Arena and Drew 1986; Grant 1986).

Hepatotoxicity

Acetone induces hepatocellular hypertrophy and dose-related increases in liver weight. It also induces microsomal enzymes that metabolize other chemicals, thereby potentially altering the toxicity of xenobiotics. These effects, however, are considered adaptive rather than adverse. The National Toxicology Program (NTP) conducted 2-week (wk) and 13-wk toxicity studies in rats and mice ingesting acetone in drinking water at concentrations of 0, 5,000, 10,000, 20,000, 50,000, and 100,000 ppm (Dietz et al. 1991; NTP 1991). The only histopathologic change as-

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

sociated with acetone exposure in both the 2-wk and the 13-wk studies was centrilobular hepatocellular hypertrophy. Male and female mice exposed to acetone at 20,000 or 50,000 ppm developed minimal-to-mild centrilobular hepatocellular hypertrophy, and male mice developed moderate centrilobular hepatocellular hypertrophy at 100,000 ppm. There were no treatment-related clinical signs of toxicity during these studies.

Hematologic Effects

Species and gender differences exist in the hematologic effects of acetone in animals. 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. 1991; NTP 1991). In mice treated for 14 d, it was not clear whether bone marrow was examined, but in the 13-wk study, no hematologic effects or histologically observable lesions in hematopoietic tissues were reported in mice (Dietz et al. 1991; NTP 1991).

CNS Toxicity

CNS effects in humans after the ingestion of acetone have been reported in cases of ingestion of large, but rarely quantified, amounts of acetone. No reports were found of CNS effects after ingestion of low doses of acetone in either humans or animals, but the following reports describe effects in humans and rats after inhalation exposure.

Dick et al. (1988, 1989) exposed 22 human volunteers to acetone at 250 ppm by inhalation for 4 h and found small but statistically significant differences from the controls in two measures of the auditory tone discrimination task (p<0.05) (a 7-14% increase in response time to detect a 760 hertz [Hz] tone in a series of 750 Hz tones and a 25% increase in false positives but no difference in the percent of correct hits) and on the anger-hostility scale (males only) of the profile of mood states (POMS) test (p<0.001). While these results are statistically significant, the small magnitude of the effects and the uncertain biologic relevance of the end points argue against using these results for the purposes of setting spacecraft water exposure guidelines (SWEGs). No other significant effects were seen in three other psychomotor tests (choice reaction time, visual vigilance, and memory scanning), one sensorimotor test (postural sway),

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

and the remaining portions of the POMS psychological test. A no-observed-adverse-effects level (NOAEL) of acetone at 125 ppm (10.4 ± 2.4 µg/mL in blood) was reported for all measured effects when the subjects were simultaneously exposed to acetone at 125 ppm and methyl ethyl ketone at 100 ppm. Measurement of acetone concentrations in venous blood indicated that the concentrations at 1.5 h postexposure (11.9 ± 2.6 µg/mL) were about 78% of the concentrations at 4 h (15.3 ± 2.9 µg/mL), and by 20 h postexposure, the acetone concentration in the blood (1.5 ± 1.0 µg/mL) had returned to pre-exposure concentrations of 2 ± 2 µg/mL. (Dick et al. 1988).

Eight men cleaning an indoor pit were exposed to acetone vapor at >12,000 ppm (Draeger tube measurements) for durations ranging from 2 minutes (min) to 4 h. Seven of the eight experienced dizziness, a feeling of inebriation, throat and eye irritation, and weakness of the legs. After three 2-min exposures, one man complained of tightness of the chest lasting for about 4 h. Two of the four men who were exposed for longer than 4 h lost consciousness (Ross 1973). One of the two men who lost consciousness was hospitalized for 4 d, but both returned to work 6 d after exposure.

The short-term operant behavior of rats exposed to acetone by inhalation was examined by Goldberg et al. (1964). Female rats were trained according to an avoidance-escape paradigm. Groups were exposed at 3,000, 6,000, 12,000, or 16,000 ppm for 4 h/d, 5 d/wk for 10 d. Body weight and growth were not affected at any dose, but escape behavior was suppressed, and ataxia was noted on day 1 in the 12,000 and 16,000 ppm groups. Avoidance behavior was inhibited in groups exposed at 6,000 ppm, 12,000 ppm, and 16,000 ppm. Tolerance to acetone developed, as evidenced by decreases in all the reported neurobehavioral effects.

Ataxia and Narcosis

Narcotic effects (lethargy, coma) have been described in several case reports of patients who had ingested acetone, but doses were unknown or only estimated (Ramu et al. 1978; Gamis and Wasserman 1988; Sakata et al. 1989). A marked disturbance of gait was observed in one patient 6 d after apparent recovery from coma caused by intentional ingestion of 200 mL of acetone (2,241 mg/kg) (Gitelson et al. 1966).

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

Bruckner and Peterson (1981) found that 4-wk-old rats and mice exposed by inhalation to acetone at 12,600-50,600 ppm for up to 3 h were slightly more sensitive to its narcotic effects than were 8- to 12-wk-old animals. The animals were scored for ataxia (seen at 12,600 ppm), immobility in the absence of stimulation (seen at 19,000 ppm), hypnosis with arousal difficult (seen at 25,300 ppm), and unconsciousness (seen at 50,600 ppm with lethality after 2 h). The degree of CNS depression was linearly related to the exposure duration for a given concentration and both the degree of CNS depression and the rapidity of its induction were dependent on the concentration of inhaled acetone. The time required for complete recovery from acetone’s CNS effects was also dependent on the concentration inhaled: 9 h were required to recover from the effects of a 3-h exposure to 19,000 ppm, and 21 h were required to recover from a 3-h exposure at 25,300 ppm (Bruckner and Peterson 1981).

Diabetic Effects

In the case described above of the man who survived ingestion of 200 mL of pure acetone (2241 mg/kg), a diabetes-like condition was reported, including hyperglycemia (2.5 mo after ingestion), polyuria, and excessive thirst (4 wk after ingestion) (Gitelson et al. 1966). According to Gitelson et al., hyperglycemia and glycosuria are commonly seen in cases of acetone poisoning. In humans, Gitelson et al. (1966) note that acetone-induced hyperglycemia appears to be consistently reversible, but after various durations of persistence.

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) ppm for 13 wk (Dietz et al. 1991; NTP 1991). Decreased water consumption was seen at ≥50,000 ppm in rats and female mice. There were no treatment-related clinical signs of toxicity during these studies.

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Neurologic Effects

No clinical or histologic evidence of neurotoxicity was observed in rats and mice ingesting acetone in drinking water at concentrations of 0, 2,500, 5,000, 10,000, 20,000, and 50,000 ppm for 13 wk (Dietz et al. 1991; NTP 1991).

Nephrotoxicity

The incidence and severity of nephropathy in male, but not female, rats (histologically identical to the chronic progressive nephropathy of aging rats) increased with increasing doses of acetone, particularly at 20,000 or 50,000 ppm in rats exposed for 13 wk (Dietz et al. 1991; NTP 1991). 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. The kidney-weight changes were associated with nephropathy.

Splenic Effects

Minimal-to-mild splenic pigmentation (hemosiderin) was seen in the splenic pulp of male rats ingesting acetone at 20,000 and 50,000 ppm (1,700 and 3,400 mg/kg/d, respectively) in drinking water for 13 wk (Dietz et al. 1991; NTP 1991).

Liver Effects

Minimal hepatocellular hypertrophy occurred in two of 10 female mice exposed to acetone at 50,000 ppm for 13 wk (Dietz et al. 1991; NTP 1991). Increased relative liver weights were seen in female mice given acetone in drinking water for 13 wk at 50,000 ppm and in both sexes of rats at ≥20,000 ppm (Dietz et al. 1991; NTP 1991). In the absence of treatment-related clinical signs of toxicity, these effects are considered adaptive rather than adverse.

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Immunologic and Hematologic Effects

No peer-reviewed reports on the immunotoxicity of acetone were found. A study that is currently available only as a conference abstract reported that acetone administration via drinking water for 28 d in accordance with the U.S. Environmental Protection Agency (EPA) Immunotoxicology Test Guideline did not produce immunotoxicity in CD-1 mice at doses as high as 1,144 mg/kg/d (acetone concentrations up to 6,000 ppm) (Anderson et al. 2004). Body weights and hematologic parameters showed no treatment-related effects because of acetone consumption.

Evidence of macrocytic anemia was seen in male rats exposed to acetone in drinking water for 13 wk (Dietz et al. 1991; NTP 1991) with a lowest-observed-adverse-effect level (LOAEL) of 400 mg/kg/d (5,000 ppm) and a NOAEL of 200 mg/kg/d (2,500 ppm). The evidence consisted of significantly decreased hemoglobin concentration, increased mean corpuscular hemoglobin and mean corpuscular volume, decreased erythrocyte counts, decreased reticulocyte counts and platelets, and splenic hemosiderosis. 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. 1986).

Carcinogenicity

There are no published studies that have assessed whether exposure to acetone is associated with an increased incidence of cancer in humans.

Genotoxicity

In studies from the NTP, acetone was not mutagenic in Salmonella typhimurium strains TA97, TA98, TA100, TA1535, or TA1537, with or without metabolic activation (NTP 1991). Acetone did not induce sister chromatid exchanges or chromosome aberrations in Chinese hamster ovary cells at doses up to 5 mg/mL with or without S9, and it did not induce micronuclei or polychromatic erythrocytes in the peripheral blood of mice ingesting acetone at 5,000-20,000 ppm in drinking water for 13 wk (NTP 1991).

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Reproductive Effects in Humans

Stewart et al. (1975) exposed 10 female volunteers to acetone vapors at 0 or 1,000 ppm for 1 h, 3 h, or 7.5 h/d for 1 wk. Three of the four female subjects exposed for 7.5 h/d experienced early menstrual periods after 4 d of exposure at 1,000 ppm.

Reproductive and Developmental Toxicity in Animals

In male rats, ingestion of acetone at a concentration of 50,000 ppm in drinking water for 13 wk resulted in depressed sperm motility, caudal epididymal weight, and epididymal weight; no significant effects were seen at 10,000 ppm (Dietz et al. 1991; NTP 1991). The relative, but not the absolute, testis weight was increased at 50,000 ppm (Dietz et al. 1991; NTP 1991). Typically, testicular toxicants decrease testes weights, so the biologic significance of these results is unclear. Acetone concentrations of 50,000 ppm produced a statistically significant increased incidence of abnormal sperm (NTP 1991).

Mast et al. (1989) reported mild developmental toxicity and mild maternal toxicity in rats exposed by inhalation to acetone at 11,000 ppm for 6 h/d, 7 d/wk during days 6-19 of gestation, but no effects were seen at 2,200 ppm. In the same study, mice exposed to acetone at 6,600 ppm for 6 h/d, 7 d/wk during days 6-17 of gestation had significant increases in resorptions and significant decreases in fetal weights. The effects on maternal weight were weak. At 2,200 ppm, no effects were seen in mice.

In the frog embryo teratogenesis assay-Xenopus (FETAX), acetone solutions increased the lethality of methylmercury chloride and trichloroethylene but increased the rate of malformations in a greater-than-additive fashion only for methylmercury chloride. Acetone solutions by themselves produced effects (96-h EC25 [effective concentration producing malformation in 25% of test embroys]) at 1.0% but not at 0.9%.

Interaction with Other Chemicals

Hepatotoxicity induced by chloroform and other haloalkanes is potentiated by previous administration of ketonic solvents, including acetone, to mice or rats (Hewitt et al. 1980). Cytochrome P4502E1 (CYP2E1) activity was reported to be induced more than 10-fold in Kupffer cells isolated from rats given acetone at 1% volume per volume

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

(v/v) in their drinking water for 7 d (Koop et al. 1991). Acetone induces hepatic cytochrome CYP2E1, which potentiated the hepatotoxicity of acetaminophen (Moldeus and Gergely 1980; Liu et al. 1991), N-nitrosodimethylamine and N-nitrosodiethylamine (Sipes et al. 1978; Lorr et al. 1984), thiobenzamide (Chieli et al. 1990), oxygen (Tindberg and Ingelman-Sundberg 1989), and chromate (Cr[VI]) (Mikalsen et al. 1991); the genotoxicity of N-nitrosodimethylamine (Glatt et al. 1981; Yoo et al. 1990); the hematotoxicity of benzene (Johansson and Ingelman-Sundberg 1988); the lethality of acetonitrile (Freeman and Hayes 1985; Freeman and Hayes 1988); and the renal toxicity of N-(3,5-dichlorophenyl) succinamide (a fungicide) (Lo et al. 1987). In male rat kidney, acetone treatment induced CYP2E1 apoprotein sixfold (Ronis et al. 1998). Lee et al. (1998) reported that rats given acetone at 5% in drinking water for 7 d had sevenfold increased activities of CYP2E1 in the liver but no such increases in the lung. CYP2E1 is involved in the metabolism of a wide variety of low molecular weight hydrocarbons and halocarbons. While the toxicity of the CYP2E1 metabolites of most compounds is lower than that of the parent compound, the metabolites of some compounds are cytotoxic, potentially mutagenic or carcinogenic.

An investigation of the pharmacologic and metabolic interactions between ethanol and several ketones, including acetone at doses of 10, 20, and 40 mmol/kg, found that acetone doses of 20 and 40 mmol/kg reduced the rate of metabolism and elimination of ethanol from the blood in male CD-1 mice and prolonged the ethanol-induced loss of righting reflex (Cunningham et al. 1989). The acetone, dissolved in corn oil, was injected intraperitoneally (ip) 30 min before the ip injection of ethanol at 4 g/kg. The mean elimination rate of ethanol from the blood was found to be markedly reduced in mice treated with acetone at 40 mmol/kg, which is thought to be related to acetone’s reduction of alcohol dehydrogenase activity.

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). The NOAEL was divided by an uncertainty factor (UF) of 100 (10 for extrapolation from animals to humans and 10 for human variability). SWEG calculations, however, do not include an intraspecies factor (for interindividual human variability in sensitivity) because the astronaut population consists of

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

healthy adults, so protection of very young or sick persons is not required.

EPA’s RfD Calculations and Rationale

The EPA’s reference dose (RfD) (see Table 1-3) was based on mild nephropathy as the critical effect, as seen only in male rats in the NTP (1991) study: “The data were analyzed using the NOAEL/LOAEL approach using a point of departure of 900 mg/kg-day based on an increased incidence of mild nephropathy. The following UFs are applied to the effect level: 10 for consideration of intraspecies variation (UFH; human variability) [not used in SWEG calculations], 3 (√10) for extrapolation for interspecies differences (UFA; animal to human), 3 (√10) to account for extrapolation from subchronic studies (UFs; subchronic to chronic), and 10 to account for a deficient database (UFD). The total UF = 10 × √10 × √10 × √10 = 1000” (EPA 2003).

RATIONALE FOR ACs

Acceptable Concentrations (ACs) 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

Organization

Exposure Limit (mg/kg/d)

Reference

Equivalent Drinking Water Concentration (mg/L)a

ATSDR

2 (intermediate duration MRL)

ATSDR 1994

50

EPA

0.9 (chronic RfD)

EPA 2003

2.5

aThe equivalent concentration of acetone in water that would yield the indicated mg/kg/d dose (MRL or RfD) for a 70-kg person drinking 2.8 L of water.

Abbreviations: ATSDR, Agency for Toxic Substances and Disease Registry; EPA, U.S. Environmental Protection Agency; MRL, minimal risk level—an estimated daily dose likely to be without risk of deleterious noncancer effects for a specified duration of exposure of the human population; RfD, reference dose—an estimated daily dose likely to be without risk of deleterious effects for a lifetime exposure of the human population.

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

TABLE 1-4 Spacecraft Water Exposure Guidelines

Duration

Concentration (ppm or mg/L)

Target Toxicity

1 d

3,500

Bone marrow hypoplasia

10 d

3,500

Bone marrow hypoplasia

100 d

150

Macrocytic anemia

1,000 d

15

Macrocytic anemia

erin deposits. ACs that protect against these effects will also protect against more-severe effects such as ataxia, immediate CNS depression, and death. Calculation using the guidelines established by the National Research Council’s (NRC’s) Committee on Toxicology (2000) to determine the highest AC for each major end point and exposure duration is documented below. If exposure data were available for both the concentration of acetone in drinking water and the daily dose (in mg/kg/d) of acetone, the ACs were calculated based on the daily dose. A SWEG value (see Table 1-4) is set for each exposure duration on the basis of the end point that yielded the lowest AC at that exposure duration. The resulting ACs for the various end points are compiled in Table 1-5 and compared.

1-d and 10-d ACs

One-d and 10-d ACs can be based on the 4,300 mg/kg/d (50,000 ppm) NOAEL for bone marrow hypoplasia in male rats after 14 d of exposure (Dietz et al. 1991; NTP 1991). Benchmark dose analysis was not appropriate for the bone marrow hypoplasia data because of the dose-response behavior; that is, the only dose at which hypoplasia was seen was the highest dose (100,000 ppm), at which 100% of test animals had hypoplasia. An interspecies UF of 10 is applied to extrapolate from rats or mice to humans. The AC is not adjusted higher for the shorter-exposure durations (1 or 10 d versus 14 d). Thus, for bone marrow hypoplasia, the AC is calculated as follows:



Because microgravity induces a reduction in red cells that would be exacerbated by bone marrow hypoplasia, the AC will be reduced by a spaceflight factor of 3. To achieve a dose rate of 430 mg/kg/d for a 70-kg

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

TABLE 1-5 Acceptable Concentrations (ACs)

 

 

 

UFs

ACs (mg/L)

End Point

Exposure Data

Species and Reference

Inter- individual

To NOAEL

Inter- species

Exposure Time

Spaceflight

1 d

10 d

100 d

1,000 d

NOAEL for bone marrow hypoplasia

4,312 mg/kg/d (50,000 ppm); 2 wk; drinking water

Rat, male (NTP 1991)

1

1

10

1

3

3,500

3,500

NOAEL for macrocytic anemia

200 mg/kg/d (2,500 ppm); 13 wk; drinking water

Rat, male (NTP 1991)

1

1

10

0.9

3

150

15

NOAEL for mild nephropathy and splenic hemosiderin

1,700 mg/kg/d (10,000 ppm); 13 wk; drinking water

Rat, male (NTP 1991)

1

1

10

0.9

1

2,000

200

SWEG

 

 

 

 

 

 

 

3,500

3,500

150

15

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

astronaut consuming 2.8 L of water per d, the concentration of acetone in the drinking water would need to be as follows:



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) (Dietz et al. 1991; NTP 1991). Above 900 mg/kg/d (10,000 ppm), mild nephropathy and splenic hemosiderosis were reported in male rats. Hepatocellular hypertrophy is considered adaptive. Therefore, ACs were calculated based on NOAELs for anemia, nephropathy, and hemosiderosis. For macrocytic anemia, the AC is calculated as follows:



Because microgravity induces a reduction in the number of red cells that would be exacerbated by bone macrocytic anemia, the AC will be reduced by a spaceflight factor of 3. For a 70-kg astronaut consuming 2.8 L of water per d, the concentration of acetone in the drinking water needed to achieve a dose rate of 20 mg/kg/d would be



A factor of 90 d/100 d = 0.9 was used to adjust the NOAEL-based AC for the difference in exposure durations between the 90-d rodent data and the 100-d astronaut exposure durations. Thus, for macrocytic anemia, the AC is calculated as follows:



For mild nephropathy and splenic hemosiderin, the AC is calculated as follows:


Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

For a 70-kg astronaut consuming 2.8 L of water per d, the concentration of acetone in the drinking water needed to achieve a dose rate of 90 mg/kg/d would be as follows:



A factor of 90 d/100 d = 0.9 was used to adjust the NOAEL-based AC for the difference in exposure durations between the 90-d rodent data and the 100-d astronaut exposure durations. Thus, for mild nephropathy and splenic hemosiderin, the AC is calculated as follows:



The odor and taste of acetone at 4,000 mg/L in drinking water is distinctly noticeable (mild) but not objectionable to all of six male test subjects (H. Garcia, National Aeronautics and Space Administration, Houston, TX, unpublished material, 2004).

1,000-d ACs

ACs for 1,000-d exposures were derived by dividing the ACs for 100-d exposures by a factor of 10 for longer-exposure duration. For macrocytic anemia, the AC is calculated as follows:



For mild nephropathy and splenic hemosiderin,



The odor and taste of acetone at 400 mg/L in drinking water were undetectable to all of six male test subjects (H. Garcia, National Aeronautics and Space Administration, Houston, TX, unpublished material, 2004).

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Reproductive Effects

After 4 d of exposure to acetone vapors at 1,000 ppm for 7 h/d, female volunteers experienced premature menstrual periods (Stewart et al. 1975). Other than transient irritation, no other adverse effects were reported (Stewart et al. 1975). The National Aeronautics and Space Administration (NASA) tests female astronauts for pregnancy before flight, and those found to be pregnant are not permitted to fly; therefore, premature menses is not considered an adverse effect and will not be used to set an AC.

Spaceflight Considerations

Microgravity is known to cause “space anemia,” a decrease in total blood volume and total number of red blood cells but no decrease in the concentration of red blood cells. The mechanism has been shown to involve increased excretion of fluid from plasma into urine and a decrease in the production of erythropoietin and, therefore, decreased production of red blood cells. However, microgravity does not appear to cause any increase in the rate of destruction of red blood cells.

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.

REFERENCES

ACGIH (American Conference of Governmental Industrial Hygienists). 1986. Acetone. Pp. 6-4 in Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th Ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.

American Biogenics Corp. 1986. Ninety-day gavage study in albino rats using acetone. Unpublished study 410-2313. American Biogenics Corp., Decatur, IL.

Anderson, P.K., M.R. Woolhiser, and J.M. Waechter. 2004. Acetone: 4-week drinking water immunotoxicity in CD-1 mice. Paper presented at the Soci-

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

ety of Toxicology 43rd Annual Conference, March 21-25, 2004, Baltimore, MD.

Arena, J.M., and R.H. Drew, eds. 1986. Poisoning: Toxicology, Symptoms, Treatments, 5th Ed. Springfield, IL: Charles C. Thomas, Publisher.

ATSDR (Agency for Toxic Substances and Disease Registry). 1994. Toxicological profile for acetone. U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA.

Baselt, R.C. 1982. Acetone. Pp. 9-10 in Disposition of Toxic Drugs and Chemicals in Man. Davis, CA: Biomedical Publications.

Bruckner, J.V., and R.G. Peterson. 1981. Evaluation of toluene and acetone inhalant abuse. I. Pharmacology and pharmacodynamics. Toxicol. Appl. Pharmacol. 61:27-38.

Chieli, E., M. Saviozzi, P. Puccini, V. Longo, and P.G. Gervasi. 1990. Possible role of the acetone-inducible cytochrome P-450IIE1 in the metabolism and hepatotoxicity of thiobenzamide. Arch. Toxicol. 64(2):122-127.

Cunningham, J., M. Sharkawi, and G.L. Plaa. 1989. Pharmacological and metabolic interactions between ethanol and methyl n-butyl ketone, methyl isobutyl ketone, methyl ethyl ketone, or acetone in mice. Fundam. Appl. Toxicol. 13:102-109.

de Oliveira, D.P., and M.E. Pereira Bastos de Siqueira. 2004. Reference values of urinary acetone in a Brazilian population and influence of gender, age, smoking and drinking. Med. Lav. 95:32-38.

Dick, R.B., W.D. Brown, J.V. Setzer, B.J. Taylor, and R. Shukla. 1988. Effects of short duration exposures to acetone and methyl ethyl ketone. Toxicol. Lett. 43:31-49.

Dick, R.B., J.V. Setzer, B.J. Taylor, and R. Shukla. 1989. Neurobehavioural effects of short duration exposures to acetone and methyl ethyl ketone. Br. J. Ind. Med. 46:111-121.

Dietz, D.D., J.R. Leininger, E.J. Raukman, M.B. Thompson, R.E. Chapin, R.L. Morrissey, and B.S. Levine. 1991. Toxicity studies of acetone administered in the drinking water of rodents. Fundam. Appl. Toxicol. 17:347-360.

DiVincenzo, G.D., F.J.Yanno, and B.D. Astill. 1973. Exposure of man and dog to low concentrations of acetone vapor. Am. Ind. Hyg. Assoc. J. 34:329-336.

EPA (U.S. Environmental Protection Agency). 2003. Acetone. In Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency, National Center for Environmental Assessment, Washington, DC [Online]. Available: http://www.epa.gov/IRIS/subst/0128.htm [accessed Feb. 24, 2005].

Finkel, A.J. 1983. Acetone. Pp. 210-211 in Hamilton and Hardy's Industrial Toxicology, 4th Ed. Boston: John Wright PSG, Inc.

Freeman, J.J., and E.P. Hayes. 1985. Acetone potentiation of acute acetonitrile toxicity in rats. J. Toxicol. Environ. Health 15:609-621.

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

Freeman, J.J., and E.P. Hayes. 1988. Microsomal metabolism of acetonitrile to cyanide. Biochem. Pharmacol. 37:1153-1159.

Gamis, A.S., and G.S. Wasserman. 1988. Acute acetone intoxication in a pediatric patient. Pediatr. Emerg. Care 4(1):24-26.

Geller, I., E.M. Gause, H. Kaplan, and R.J. Hartmann. 1979a. Effects of acetone, methyl ethyl ketone and methyl isobutyl ketone on a match-to-sample task in the baboon. Pharmacol. Biochem. Behav. 11:401-406.

Geller, I., R.J. Hartmann, S.R. Randle, and E.M.Gause. 1979b. Effects of acetone and toluene vapors on multiple schedule performance of rats. Pharmacol. Biochem. Behav. 11:395-399.

Gitelson, S., A. Werczberger, and J.R. Herman. 1966. Coma and hyperglycemia following drinking of acetone. Diabetes 15:810-811.

Glatt, J., L. DeBalle, and F. Oesch. 1981. Ethanol- or acetone-pretreatment of mice strongly enhances the bacterial mutagenicity of dimethylnitrosamine in assays mediated by liver subcellular fraction, but not in host-mediated assays. Carcinogenesis 2:1057-1067.

Goldberg, M.E., H.E. Johnson, U.C. Pozzani, and F.H. Smyth, Jr. 1964. Effect of repeated inhalation of vapors of industrial solvents on animal behavior. Evaluation of nine solvent vapors on pole-climb performance in rats. Am. Ind. Hyg. Assoc. J. 25:369-375.

Gosselin, R.E., R.P. Smith, and H.C. Hodge. 1984. Clinical toxicology of commercial products, 5th ed. Baltimore, MD: Williams & Wilkins.

Grant, M. 1986. Acetone. Pp. 41-42. In Toxicology of the Eye, 3rd Ed. Springfield, IL: Charles C. Thomas, Publisher.

Haggard, H.W., L.A. Greenberg, and J.M. Turner. 1944. The physiological principles governing the action of acetone together with determination of toxicity. J. Ind. Hyg. Toxicol. 26:133-151.

Hallier, E., J.G. Filser, and H.M. Bolt. 1981. Inhalation pharmacokinetics based on gas uptake studies. II. Pharmacokinetics of acetone in rats. Arch. Toxicol. 47:293-304.

Hewitt, W.R., H. Miyajima, M.G. Coté, and G.L. Plaa. 1980. Modification of haloalkane-induced hepatotoxicity by exogenous ketones and metabolic ketosis. Fed. Proc. 39:3118-3123.

HSDB (Hazardous Substances Data Bank). 2006. Acetone. U.S. National Library of Medicine. [Online]. Available at: http://toxnet.nlm.nih.gov/cgibin/sis/search/f?/temp/~RqiGV0:1 [access September 5, 2006].

Inoue, R. 1983. Acetone and derivatives. Pp. 38-39 in Encyclopedia of Occupational Health and Safety, 3rd Rev. Ed. L. Parmeggiani, ed. Geneva, Switzerland: International Labour Organization.

Johansson, I., and M. Ingelman-Sundberg. 1988. Benzene metabolism by ethanol-, acetone-, and benzene-inducible cytochrome P-450 (IIE1) in rat and rabbit liver microsomes. Cancer Res. 48:5837-5890.

Jones, A.W. 2000. Elimination half-life of acetone in humans: Case reports and review of the literature. J. Anal. Toxicol. 24(1):8-10.

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

Koop, D.R., A. Chernosky, and E.P. Brass. 1991. Identification and induction of cytochrome P450 2E1 in rat Kupffer cells. J. Pharmacol. Exp. Ther. 258(3):1072-1076.

Krasavage, W.J. , J.L. O'Donoghue, and G.D. DiVincenzo. 1982. Ketones. Pp. 4709-4727 in Patty's Industrial Hygiene and Toxicology, 3rd Rev. Ed. G.D.Clayton, and F.E.Clayton, eds. New York: John Wiley & Sons.

Lee, C., K.C. Watt, A.-M. Chan, C.G. Plopper, A.R. Buckpitt, and K.E. Pinkerton. 1998. Site-selective differences in cytochrome P450 isoform activities. Drug. Metab. Dispos. 26(5):396-400.

Liebich, H.M., W. Bertsch, A. Zlatkis, and H.J. Schneider. 1975. Volatile organic components in the Skylab 4 spacecraft atmosphere. Aviat. Space Envir. Med. 46(8):1002-1007.

Liu, J., C. Sato, and F. Marumo. 1991. Characterization of the acetominophenglutathione conjugation reaction by liver microsomes: Species difference in the effects of acetone. Toxicol. Lett. 56:269-274.

Lo, H.H., V.J. Teets, D.J. Yang, P.I. Brown, and G.O. Rankin. 1987. Acetone effects on N-(3,5-dichlorophenyl)succinamide-induced nephrotoxicity. Toxicol. Lett. 38:161-168.

Löf, A., M. Nordqvist, and E. Wigaeus. 1980. Inhalation exposure of mice to acetone. Toxicol. Lett. Special Issue 1:213.

Lorr, N.A., K.W. Miller, H.R. Chung, and C.S. Yang. 1984. Potentiation of the hepatotoxicity of N-nitrosodimethylamine by fasting, diabetes, acetone, and isopropanol. Toxicol. Appl. Pharmacol. 73(3):423-431.

Mast, T.J., R.L. Rommereim, R.J. Weigel, R.B. Westerberg, B.A. Schwetz, and R.E. Morrissey. 1989. Developmental toxicity study of acetone in mice and rats. Teratology 39(5):468.

Matsushita, T., E. Goshima, H. Miyagaki, K. Maeda, Y. Takeuchi, and T. Inoue. 1969. Experimental studies for determining the maximum permissible concentration of acetone-2. Biological reaction in the six-day exposure to acetone. Sangyo Igaka (Jpn. J. Ind. Health) 11:507-511.

Mikalsen, A., J. Alexander, R.A. Anderson, and M. Ingelman-Sundberg. 1991. Effect of in vivo chromate, acetone and combined treatment on rat liver in vitro microsomal chromium (VI) reductive activity and on cytochrome P450 expression. Pharmacol. Toxicol. 68:456-463.

Mirchev, N. 1977. Hepatorenal lesions after acute acetone intoxication. Vutr. Boles. 17:89-92.

Moldeus, P., and V. Gergely. 1980. Effect of acetone on the activation of acetaminophen. Toxicol. Appl. Pharmacol. 53:8-13.

Nelson, D.L., and B.P. Webb. 1978. Acetone. Pp. 179-191 in Kirk-Othmer Encyclopedia of Chemical Toxicology, 3rd Ed. New York: John Wiley & Sons.

NTP (National Toxicology Program). 1991. Toxicity studies of acetone (CAS No. 67-64-1) in F344/N rats and B6C3F1 mice (drinking water studies). NTP TOX3, NIH Publication No. 91-3122. NTP, Research Triangle Park, NC.

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

OSHA (Occupational Safety and Health Administration). 1989. Acetone [online]. Available: www.cdc.gov/niosh/pel88/67-64.html [accessed Jan. 25, 2005].

Ramu, A., J. Rosenbaum, and T. Blaschke. 1978. Disposition of acetone following acute acetone intoxication. West. J. Med. 129(5):429-432.

Ronis, M.J.J., J. Huang, V. Longo, N. Tindberg, M. Ingelman-Sundberg, and T.M. Badger. 1998. Expression and distribution of cytochrome P450 enzymes in male rat kidney: Effects of ethanol, acetone and dietary condition—assay and product identification by thin layer chromatography. Biochem. Pharmacol. 55(2):123-129.

Ross, D.S. 1973. Acute acetone intoxication involving eight male workers. Ann. Occup. Hyg. 16:73-75.

Rowe, V.K., and M.A. Wolf. 1963. Ketones. Pp. 1719-1731 in Patty's Industrial Hygiene and Toxicology, 2nd Rev. Ed. G.D. Clayton, and F.E. Clayton, eds. New York: John Wiley & Sons.

Sakata, M., J. Kikuchi, and M. Haga. 1989. Disposition of acetone, methyl ethyl ketone and cyclohexanone in acute poisoning. Clin. Toxicol. 12(1-2):67-77.

Sipes, I.G., M.L. Slocumb, and G. Holtzman. 1978. Stimulation of microsomal dimethylnitrosamine-N-demethylase by pretreatment of mice with acetone. Chem. Biol. Interact. 21:155-166.

Stewart, R.D., C.L. Hake, A. Wu, S.A. Graff, H.V. Forster, W.H. Keeler, A.J. Lebrun, P.E. Newton, and R.J. Soto. 1975. Acetone: Development of a biologic standard for the industrial worker by breath analysis. Cincinnati, OH: National Institute for Occupational Safety and Health.

Tindberg, N., and M. Ingelman-Sundberg. 1989. Cytochrome P-450 and oxygen toxicity.Oxygen-dependent induction of ethanol-inducible cytochrome P-450 (IIE1) in rat liver and lung. Biochemistry 28:4499-4504.

Wang, G., G. Maranelli, L. Perbellini, E. Raineri, and F. Brugnone. 1994. Blood acetone concentration in "normal people" and in exposed workers 16 h after the end of the workshift. Int. Arch. Occup. Environ. Health 65:285-289.

Widmark, E. 1919. Studies in the concentration of indifferent narcotics in blood and tissues. Acta Med Scand. 52:87-164.

Wigaeus, E., S. Holm, and I. Estrand. 1981. Exposure to acetone. Uptake and elimination in man. Scand J. Work Environ. Health 7:84-94.

Wigaeus, E., A. Löf, and M. Nordqvist. 1982. Distribution and elimination of 2-[14C]-acetone in mice after inhalation exposure. Scand. J. Work Environ. Health 8(2):121-128.

Windholz, M. 1983. Acetone. P. 2 in Merck Index, 9th Ed. M. Windholz, and N.J. Rahway, eds. Rahway, New Jersey: Merck & Co.

Yoo, J.S.H., H. Ishizaki, and C.S. Yang. 1990. Roles of cytochrome-P450IIE1 in the dealkylation and denitrosation of N-nitrosodiethylamine in rat liver microsomes. Carcinogenesis 7:2239-2243.

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×

Zettinig, G., N. Watzinger, B. Eber, G. Henning, and W. Klein. 1997. Survival after poisoning due to intake of ten-times lethal dose of acetone [in German]. Dtsch. Med. Wochenschr. 122(48):1489-1492.

Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 9
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 10
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 11
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 12
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 13
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 14
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 15
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 16
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 17
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 18
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 19
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 20
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 21
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 22
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 23
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 24
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 25
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 26
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 27
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 28
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 29
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 30
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 31
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 32
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 33
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 34
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 35
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 36
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 37
Suggested Citation:"Appendix 1 Acetone." National Research Council. 2007. Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2. Washington, DC: The National Academies Press. doi: 10.17226/11778.
×
Page 38
Next: Appendix 2 Ammonia »
Spacecraft Water Exposure Guidelines for Selected Contaminants: Volume 2 Get This Book
×
Buy Paperback | $138.00 Buy Ebook | $109.99
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF
  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!