The Risk Assessment Information System

Toxicity Summary for ACETONE

NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.

Download

EXECUTIVE SUMMARY

1. INTRODUCTION

2. METABOLISM AND DISPOSITION

2.1 ABSORPTION
2.2 DISTRIBUTION
2.3 METABOLISM
2.4 EXCRETION

3. NONCARCINOGENIC HEALTH EFFECTS

3.1 ORAL EXPOSURES
3.2 INHALATION EXPOSURES
3.3 OTHER ROUTES OF EXPOSURE
3.4 TARGET ORGANS/CRITICAL EFFECTS

4. CARCINOGENICITY

4.1 ORAL EXPOSURES
4.2 INHALATION EXPOSURES
4.3 OTHER ROUTES OF EXPOSURE
4.4 EPA WEIGHT-OF-EVIDENCE
4.5 CARCINOGENICITY SLOPE FACTORS

5. REFERENCES

May 1995

Prepared by Dennis M. Opresko, Ph.D., Chemical Hazard Evaluation Group, Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, *, Oak Ridge, Tennessee.

Prepared for OAK RIDGE RESERVATION ENVIRONMENTAL RESTORATION PROGRAM

*Managed by Lockheed Martin Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400

EXECUTIVE SUMMARY

Acetone (CAS No. 67-64-1) is a clear, colorless, highly flammable liquid with a vapor pressure of 182 mm Hg at 20C (Morgott, 1993). It is completely miscible in water and soluble in organics such as benzene and ethanol (ATSDR, 1994). Its log K_ow has been estimated to be -0.24 (ATSDR, 1994). Acetone is used primarily as a solvent and chemical intermediate, and it is also found in some consumer products such as nail polish remover (Inoue, 1983; Kumai et al., 1983).

Acetone may be released into the environment as stack emissions and/or fugitive emissions and in waste water effluents from facilities involved in its production and use as a chemical intermediate and solvent (HSDB, 1995). Acetone is also a natural metabolic byproduct found in and released from plants and animals. Much of the acetone released into the environment will volatilize into the atmosphere where it will be subject to photo-oxidation (average half-life is 22 days). Volatilization from surface waters is moderately rapid (estimated half-life about 20 hours from a model river). If released onto the ground, acetone will both volatilize and leach into the soil and relatively little will be adsorbed to soil particles (HSDB, 1995). Acetone has been detected in groundwater and drinking water.

Acetone can be absorbed through the lungs, digestive tract, and the skin (Morgott, 1993). It is rapidly transported throughout the body and is not preferentially stored in any body tissue (Morgott, 1993). The liver is the major organ of acetone metabolism, and excretion occurs mainly through the lungs and in the urine.

Acute toxic effects following ingestion of 50 mL or more may include ataxia, sedation, and coma; respiratory depression; gastrointestinal disorders (vomiting and hematemesis); hyperglycemia and ketonemia; acidosis; and hepatic and renal lesions (Krasavage et al., 1982). Ingestion of 10-20 mL (7.9-15.8 g) generally is not toxic (HSDB, 1995), and consumption of 20 g/day for several days resulted in only slight drowsiness (Morgott, 1993). The minimum lethal dose for a 150-lb man is estimated to be 100 mL (79.1 g). No information is available on the subchronic or chronic oral toxicity to humans. In animal studies, subchronic oral exposures were associated with kidney damage and hematological changes.

The reference dose (RfD) for chronic oral exposures, 0.1 mg/kg/day (EPA, 1995), is based on increased liver and kidney weights and nephrotoxicity in rats (EPA, 1986). The subchronic oral RfD of 1 mg/kg/day (EPA, 1994) is based on the same rodent study.

Information on the inhalation toxicity of acetone to humans is derived from occupational and laboratory studies. Typical symptoms of inhalation exposure are central nervous system depression and irritation of the mucous membranes of the eyes, nose, and throat (Morgott, 1993). Central nervous system effects can range from subtle neurobehavioral changes to narcosis depending on the magnitude and length of exposure. Neurobehavioral changes have been reported at concentrations as low as 237 ppm (574 mg/m³) (Dick et al., 1989). Irritant effects have been reported at concentrations of 500 ppm (1210 mg/m³) and higher. Transient effects were reported in workers exposed to 600-2150 ppm (1452-5203 mg/m³) (EPA, 1995). Extremely high concentrations (> 29 g/m³) can cause dizziness, confusion, unsteadiness, and unconsciousness (ATSDR, 1994). Prolonged occupational exposures to acetone vapors have not been associated with chronic systemic disorders (Morgott, 1993).

Studies have shown that acetone vapor concentrations in excess of 8000 ppm (19.36 mg/m³) are generally required to produce signs of central nervous system depression in animals, but concentrations as low as 500 ppm (1210 mg/m³) may cause subtle behavioral changes (Morgott, 1993; ATSDR, 1994). Little information is available on subchronic or chronic inhalation toxicity in animals.

An inhalation reference concentration (RfC) has not been derived for acetone (EPA, 1995).

Animal data indicate that acetone is not teratogenic; however, adverse reproductive effects may occur at high concentrations. Drinking water concentrations equal to doses >3 g/kg/day during pregnancy were associated with spermatogenic effects, reduced reproductive index, and decreased pup survival of rodents (Larsen et al., 1991; EHRT, 1987). Inhalation exposure to 11,000 ppm resulted in reduction in maternal body weight gain, a decrease in uterine and extragestational weight gain, and a significant reduction in fetal weight of rats but no adverse effects on reproduction or development (Mast et al., 1988). In the latter study, the incidence of malformations was not increased by exposure to acetone.

No evidence is available that suggests acetone is carcinogenic in humans or animals (Morgott, 1993). Negative results have been reported in occupational exposure studies and in rodent skin painting studies. Although acetone has not been tested in a 2-year rodent bioassay, in vitro tests for mutagenicity, chromosome damage, and DNA interaction indicate that acetone is not genotoxic except under severe conditions (Morgott, 1993). Acetone is classified by EPA in weight-of-evidence Group D, not classifiable as to human carcinogenicity (EPA, 1995).

1. INTRODUCTION

Acetone (CAS No. 67-64-1) is a clear, colorless, highly flammable liquid with a vapor pressure of 182 mm Hg at 20C (Morgott, 1993). It has a molecular weight of 58.08, a density of 0.799 g/mL at 20C, and a log K_ow of -0.24. It is completely miscible in water and is soluble in benzene and ethanol (ATSDR, 1994; Morgott, 1993). It is used as a solvent in paints, inks, adhesives, thinners, degreasers, varnishes, and lacquers and also as a chemical intermediate in the production of lubricating oils, chloroform, and various pharmaceuticals and pesticides (U.S Air Force, 1989). Although most products containing acetone are used by industry, some acetone products, such as nail polish remover, paint remover, glue, and cleaning agents, are used by consumers (Inoue, 1983; Kumai et al., 1983; ATSDR, 1994).

Acetone may be released into the environment as stack emissions and/or fugitive emissions and in waste water effluents from facilities involved in its production and use as a chemical intermediate and solvent; in volcanic eruptions, forest fires, automobile exhaust, and tobacco smoke; from burning of wood and polyethylene; from landfills; and from plants and animals in which it occurs as a natural metabolic byproduct (HSDB, 1993; ATSDR, 1994). Because of its volatility and solubility, acetone can be found in the atmosphere and in natural water bodies. In the atmosphere, acetone will be subject to photolysis and reaction with photochemically produced hydroxyl radicals (combined half-life about 22 days on average). In surface waters, acetone is subject to biodegradation and volatilization (estimated half-life 20 hours from a model river). If released onto the ground, acetone may volatilize or leach into the soil where it likely will be subject to biodegradation (HSDB, 1995).

2. METABOLISM AND DISPOSITION

2.1 ABSORPTION

Acetone can be absorbed through the lungs, digestive tract, and skin (Morgott, 1993). Information on gastrointestinal absorption rates was not found in the available literature. Pulmonary absorption in humans can be quite high. A man breathing 9300 ppm (22 g/m³) for 5 minutes absorbed 71% of the inhaled chemical; two men breathing 4650 ppm (11 g/m³) for 15 minutes absorbed 76 and 77% (Krasavage et al., 1982). Tada et al. (1972) reported that humans exposed to 600 ppm (1425 mg/m³) absorbed 83% of the dose. Wigaeus et al. (1981) reported pulmonary absorption rates of 39-52% for exposure levels of 300 or 552 ppm. Absorption of acetone vapors through the skin is negligible; however, dermal uptake may occur following prolonged contact with the undiluted liquid (EPA, 1980).

2.2 DISTRIBUTION

Acetone is readily absorbed into the blood and rapidly transported throughout the body (Morgott, 1993). It is evenly distributed between the cellular and noncellular fractions (Mizunuma et al., 1993) and is not preferentially stored in any body tissue (Morgott, 1993).

2.3 METABOLISM

The liver is the major organ of acetone metabolism; however, little metabolism occurs after administration of large doses (EPA, 1980). Acetone is metabolized by three separate gluconeogenic pathways, leading to the production of glucose with subsequent liberation of carbon dioxide (ATSDR, 1994).

2.4 EXCRETION

Acetone is excreted mainly through the lungs and urine. Excretion is rapid following a single oral dose but may not be complete in 24 hours; 40-70% may be excreted through the lungs, 15-30% in the urine, and 10% through the skin (Krasavage et al., 1982). Injection of 5 g/hour into humans resulted in a slow rate of excretion (EPA, 1980).

3. NONCARCINOGENIC HEALTH EFFECTS

3.1 ORAL EXPOSURES

3.1.1 Acute Toxicity

3.1.1.1 Human

Acetone acts primarily as a depressant of the central nervous system. Signs of toxicity following severe intoxication may include ataxia, sedation, and coma (HSDB, 1995). Respiratory depression, gastrointestinal disorders (vomiting and hematemesis), hyperglycemia and ketonemia, acidosis and hepatic and renal damage may also occur (HSDB, 1995). Ingestion of 10-20 mL (8-16 g) is generally not toxic (Widmark, 1919); consumption of 20 g/day for several days resulted in slight drowsiness (Morgott, 1993). A dose of 50 mL (40 g) or more may produce toxic effects (Verschueren, 1983). The minimum lethal dose for a 150-lb man is estimated to be 100 mL (80 g) (Arena and Drew, 1986). A individual who drank about 200 mL of pure acetone (160 g or about 2.2 g/kg) exhibited shallow respiration, a red and swollen throat, erosions in the soft palate and esophagus, and elevated blood glucose levels and became comatose for 12 hours (Gitelson et al., 1966).

3.1.1.2 Animal

Oral LD₅₀ values of 3.0 and 5.25 g/kg for mice, 5.8-9.8 g/kg for rats, and 5.34 g/kg for rabbits have been reported (Sax, 1984; Morgott, 1993; RTECS, 1995). A dose of 10 mL/kg (about 8 g/kg) was reported to be lethal to rabbits and dogs (Verschueren, 1983). Kimura et al. (1971) reported LD₅₀ values of 1.8, 4.5, 7.3, and 6.8 g/kg for newborn, immature, young adult, and old adult rats, respectively. A single gavage dose of 871 mg/kg resulted in degeneration of the apical microvilli in the renal tubules of rats (Brown and Hewitt, 1984). Signs of narcosis and changes in respiration were observed in rabbits and dogs dosed with about 4 g acetone/kg (ATSDR, 1994).

The toxicity of acetone to male and female F344/N rats and B6C3F₁ mice was evaluated in a 14-day drinking water study (NTP, 1991; see also Dietz et al., 1991). Test concentrations ranged from 5000 to 100,000 ppm. The time-weighted average doses for the various test groups ranged from 714 to 6942 mg/kg/day for male rats, 751 to 8560 mg/kg/day for female rats, 965 to 10,314 mg/kg/day for male mice, and 1569 to 12,725 mg/kg/day for female mice. Survival rates were not affected by exposure to acetone. Increased liver weights occurred in male mice at doses >=9659 mg/kg/day and in female mice at >=5481 mg/kg/day. Centrilobular hepatocellular hypertrophy was observed in male mice receiving >=3896 mg/kg/day and in female mice receiving 8804 mg/kg/day. Five of five male rats dosed with 6942 mg/kg/day developed bone marrow hypoplasia. Hypoplasia was not seen in female rats or in males exposed to <=4312 mg/kg/day.

Rats exposed for 6 weeks to acetone in their drinking water (concentration equivalent to a dose of 650 mg/kg/day) exhibited a decrease in motor nerve conduction velocity (Ladefoged et al., 1989).

3.1.2 Subchronic Toxicity

3.1.2.1 Human

Information on the effects of acetone in humans following subchronic oral exposures was not found in the available literature.

3.1.2.2 Animal

The oral toxicity of acetone to albino rats was evaluated in a 90-day gavage study in which the test animals (30/sex/group) were dosed with 0, 100, 500, or 2500 mg/kg/day (EPA, 1986). No adverse effects were seen in rats dosed with 100 mg/kg/day. In the 500 mg/kg group, statistically significant increases in kidney weight occurred in females and significant increases in the severity of renal tubular degeneration and hyaline droplet accumulation occurred in males. In the high-dose groups, significant increases were observed in absolute kidney weight (females), relative kidney weight (males and females), in absolute and relative liver weights (males and females), and in the severity of renal tubular degeneration (males and females). In addition, both males and females dosed with 2500 mg/kg/day exhibited hematological changes (increased hemoglobin, hematocrit, mean cell hemoglobin, mean cell volume and platelets), decreased brain weight, excessive salivation, and increased serum alanine aminotransferase.

The effects of a 13-week exposure of male and female F344/N rats and B6C3F₁ mice to acetone administered in drinking water were evaluated by NTP (1991; see also Dietz et al., 1991). Test concentrations ranged from 2500 to 50,000 ppm in the rat study and 1250-20,000 ppm (males) or 2500-50,000 ppm (females) in the mouse study. Exposure to acetone did not affect the survival rates of either species. In rats, signs of possible toxic effects occurred mainly at 20,000 and 50,000 ppm and included decreases in body and relative organ weights (kidney, liver, lung, and testis), mild macrocytic anemia (decreases in hemoglobin, erythrocytes, reticulocytes, and platelets, and increases in mean corpuscular hemoglobin, mean cell volume, leukocytes, and lymphocytes), hemosiderosis of the spleen, testicular changes (decreases in caudal and right epididymal weight and sperm motility and an increase in abnormal sperm), and an increased incidence and severity of nephropathy. It was noted that although nephropathy is a spontaneously occurring, progressive condition in rats, exposure to acetone caused a more severe response. The only significant effects seen in the mouse study were increases in absolute and relative liver weights and a minimal degree of centrilobular hepatocellular hypertrophy in two of five females receiving drinking water with 50,000 ppm acetone (equivalent to 11,298 mg/kg/day).

Rats exposed to 25,000 ppm acetone in drinking water for 18 weeks exhibited no adverse effects except for weight loss (EPA, 1984). Rats administered 0.5% acetone in their drinking water for 8 weeks followed by 1.0% for an additional 4 weeks did not exhibit any histopathological changes in central, peripheral, or distal axons (Spencer et al., 1978).

3.1.3 Chronic Toxicity

3.1.3.1 Human

Information on the effects of acetone in humans following chronic oral exposures was not found in the available literature.

3.1.3.2 Animal

Information on the effects of acetone in animals following chronic oral exposures was not found in the available literature.

3.1.4 Developmental and Reproductive Toxicity

3.1.4.1 Human

Information on the reproductive and/or developmental effects of acetone in humans following oral exposures was not found in the available literature.

3.1.4.2 Animal

Administration of 3500 mg acetone/kg/day by gavage (in water) to female mice on gestation days 6 to 15 resulted in reduced maternal body weight, increased gestation duration, reduced reproductive index, and decreased survival of pups (EHRT, 1987).

Rats provided with drinking water containing acetone at a concentration equivalent to a dose of 1071 mg/kg/day for 6 weeks exhibited no adverse effects (Larsen et al., 1991); however, drinking water containing 5% acetone (equivalent to 3.1 g acetone/kg/day) was associated with mild adverse spermatogenic effects after 13 weeks exposure (Dietz et al., 1991).

3.1.5 Reference Dose

3.1.5.1 Subchronic

• ORAL RfD: 1 mg/kg/day (EPA, 1994)
• UNCERTAINTY FACTOR: 100
• NOAEL: 100 mg/kg/day
• PRINCIPAL STUDY: EPA, 1986
• COMMENT: The same study applies to the chronic RfD (see Sect. 3.1.5.2).

3.1.5.2 Chronic

• ORAL RfD: 0.1 mg/kg/day (EPA, 1995)
• UNCERTAINTY FACTOR: 1000
• MODIFYING FACTOR: 1
• NOAEL: 100 mg/kg/day
• CONFIDENCE:
  Study: Medium
  Data Base: Low
  RfD: Low
• VERIFICATION DATE: 05/30/86
• PRINCIPAL STUDY: EPA, 1986
• COMMENT: Based on a 90-day gavage study in rats (EPA, 1986), critical effects and increased liver and kidney weights are possible effects. Note: the oral RfD for acetone may change in the near future pending the outcome of a further review now being conducted by the RfD/RfC Work Group (EPA, 1995).

3.2 INHALATION EXPOSURES

3.2.1 Acute Toxicity

3.2.1.1 Human

Typical symptoms of exposure to acetone are central nervous system depression and irritation of the mucous membranes of the eyes, nose, and throat (Morgott, 1993). Central nervous system effects can range from subtle neurobehavioral changes to narcosis depending on the magnitude and length of exposure. Individuals exposed for 4 hours to 237 ppm (574 mg/m³) exhibited significant changes from controls in performance, as measured by auditory tone discrimination (increased response time and increased false alarms), and in anger and hostility (Dick et al., 1989). Neurological effects, as indicated by lack of energy, general weakness, delayed visual reaction time, and headache, were observed in individuals exposed to 250 ppm (605 mg/m³) for 5.25 hours once or repeatedly, 6 times/day for 6 days (Matsushita et al., 1969a, 1969b). Exposure to 1250 ppm (3025 mg/m³), 1-7.5 hours/day, 2-5 days/week for 6 weeks reportedly caused an increased visual-evoked response in test subjects (Stewart et al., 1975). A concentration of 2000 ppm (4840 mg/m³) for 5 minutes may be sufficient to produce a slight narcotic effect (Inoue, 1983), and >12,000 ppm for several minutes to 4 hours reportedly caused dizziness, confusion, unsteadiness, and unconsciousness in workers occupationally exposed (Ross, 1973).

Although respiration tract irritation was reported to have occurred at an acetone concentration as low as 100 ppm (242 mg/m³) (Matsushita et al., 1969a), most data indicate that irritant effects occur at higher exposure levels only; i.e., 250 ppm, 6 hours/day for 6 days; 500 ppm (1210 mg/m³) for 6 hours; 800 ppm (1936 mg/m³) for 60 minutes; about 1000 ppm (2420 mg/m ³) for 8 hours; or 600-2150 ppm acetone (1452-5203 mg/m³) during occupational exposures (Matsushita et al., 1969b; Verschueren, 1983; Morgott, 1993; EPA, 1995). Exposure to 9300 ppm (22,506 mg/m³) for 5 minutes reportedly was intolerable because of throat irritation (Inoue, 1983).

Exposure to 500 ppm (1210 mg/m³), 6 hours per day for 6 days, was associated with an increase in leukocyte and eosinophil counts and a decrease in phagocytic activity of neutrophils (Matsushita, 1969b). A concentration of 250 ppm (605 mg/m³) caused only slight blood changes.

3.2.1.2 Animal

Studies have shown that acetone vapor concentrations in excess of 8000 ppm are generally required to cause signs of central nervous system depression in animals, but lower concentrations may cause subtle behavioral changes (Morgott, 1993; ATSDR, 1994). Baboons exposed to 500 ppm (1210 mg/m³), 6 hours/day for 7 days, exhibited marked behavioral changes as measured by their response to a match-to-sample discrimination task (Geller et al., 1979). Rats exposed to 2600-3000 ppm for 4 hours exhibited a significant delay in response time in a "behavioral despair" swimming test (Garcia et al., 1978). Mice exposed to 3000 ppm for one day showed a decreased response to food presentation in a fixed-interval operant behavioral test (Glowa and Dews, 1987). Rats exposed to 6000 ppm (14,520 mg/m³) for 4 hours/day, 5 days/wk for 2 weeks exhibited a significant modification of avoidance and escape behavior patterns (Goldberg et al., 1964).

Neurological effects seen at concentrations above 8000 ppm include: (1) severe narcosis in pregnant mice exposed to 11,000 ppm for 6 hours (NTP, 1988); (2) transient ataxia in female CFE rats exposed to 12,000 ppm (29,040 mg/m³), 5 days/week for 2 weeks (Grasso et al., 1984); (3) a decline in performance scores in rats after a 3-hour exposure to >=12,600 ppm (De Ceaurriz et al., 1984); (4) drowsiness, staggering, prostration, clonic movements of the hind legs, and deep narcosis in mice exposed to 16,839 ppm for 4 hours (Mashbitz et al., 1936); (5) loss of reflexes in guinea pigs after 8 or 9-hour exposure to 20,000 ppm (48,400 mg/m³); (6) central nervous system depression in mice exposed to 20,256 ppm (49,020 mg/m³) for 1.5 hours (Krasavage et al., 1982; Morgott, 1993); (7) central nervous system depression, decreased respiratory and heart rates, paralysis, and coma in guinea pigs exposed to 21,800 ppm (52,756 mg/m³) for periods ranging from 25 minutes to 24 hours (Specht et al., 1939); (8) loss of corneal reflex in rats following exposure to 42,200 ppm (102,124 mg/m³) for 1.75-2.0 hours; and (9) unconsciousness in mice exposed to 42,200-84,400 ppm for 35 minutes (Mashbitz et al., 1936).

Lethal exposure levels have been recorded for several species. Exposure to 46,000 ppm (111,320 mg/m³) for 1 hour (Krasavage et al., 1982), 16,000 ppm (38,720 mg/m³) for 4 hours, or 50,600 ppm (122,452 mg/m³) for 2 hours was lethal to rats, and 50,000 ppm (121,000 mg/m³) for 3-4 hours was lethal to guinea pigs (ATSDR, 1994). An 8-hour LC₅₀ of 50,100 mg/m³ has been reported for rats (Pozzani et al., 1959). In guinea pigs, lethal exposure levels (50,000 ppm) cause pulmonary congestion and hemorrhage and damage to the kidneys and spleen (Specht et al., 1939).

Decreases in respiratory and heart rates were recorded in guinea pigs exposed to 4800 ppm (11,616 mg/m³) (Specht et al., 1939). Histological examination revealed congestion of the lungs and kidney as well as hemorrhaging in the pulp of the spleen.

3.2.2 Subchronic Toxicity

3.2.2.1 Human

Humans repeatedly exposed to >750 ppm acetone (>1782 mg/m³) in an occupational setting reported irritation of the mucous membranes including conjunctivitis, pharyngitis, inflammatory bronchitis, and gastroduodenitis (Raleigh and McGee, 1972).

3.2.2.2 Animal

Rats exposed to 19,000 ppm acetone (45,980 mg/m³) for 3 hours/day, 5 days/week for 8 weeks exhibited narcosis and decreased body weights, but there were no changes in clinical chemistry parameters or histological appearance of the liver, brain, lungs, or heart (Bruckner and Peterson, 1981).

3.2.3 Chronic Toxicity

3.2.3.1 Human

The available data indicate that individuals occupationally exposed to acetone may exhibit transient symptoms of toxicity; however, there is little evidence of permanent systemic damage even after many years of exposure. Ott et al. (1983a, 1983b) examined the mortality rates and clinical chemistry data for 948 employees in a cellulose fiber production plant who were exposed to 380, 770, or 1070 ppm acetone (median TWAs; 920, 1863, and 2589 mg/m³, respectively) over a span of 23 years and found that there were no statistical differences from control values in observed deaths from all causes, cardiovascular disease, or selected hematologic or clinical chemistry measurements. Hematologic and clinical chemistry parameters were also measured by Grampella et al. (1987) in two groups of workers in an acetate fiber manufacturing facility who were exposed to 549-653 ppm (1329-1580 mg/m³) and 948-1048 ppm (2294-2536 mg/m³) acetone, respectively, for at least 5 years. No significant differences were seen in either group when compared to an unexposed control group.

Oglesby et al. (1949) evaluated the incidence of illness among employees of a cellulose acetate production facility exposed to acetone over a span of 18 years. Mild transient symptoms of irritation occurred when average exposure concentrations exceeded 2500 ppm (6050 mg/m³), but concentrations up to 1500 ppm (3630 mg/m³) appeared to be without deleterious effects.

3.2.3.2 Animal

Information was not found in the available literature on the chronic toxicity of acetone in animals following inhalation exposures.

3.2.4 Developmental and Reproductive Toxicity

3.2.4.1 Human

Limited information was found in the available literature on the developmental/reproductive effects of acetone in humans following inhalation exposures. Premature menstrual periods were reported by three of four women exposed to 1000 ppm (2420 mg/m³) acetone for 7.5 hours (Stewart et al., 1975). In an epidemiological study of female laboratory workers exposed to various solvents including acetone, there was no statistically significant difference in the incidence of miscarriage when compared to controls (Axelsson et al., 1984).

3.2.4.2 Animal

The potential developmental/reproductive effects of acetone have been evaluated in tests on rats and mice (Mast et al., 1988). Mated rats were exposed 6 hours/day to 0, 440, 220, or 11,000 ppm acetone on days 6-19 of gestation. Mice were exposed to 0, 440, 2200, or 6600 ppm on days 6-17 of gestation. In rats, exposure to 11,000 ppm (26,620 mg/m³) resulted in reduction in maternal body weight gain, a decrease in uterine and extragestational weight gain of the dams, and a significant reduction in fetal weight, but no adverse effects on reproduction or development were noticed, although the percentage of litters with at least one pup exhibiting a malformation was greater than that of the control group. In mice, exposure to 6600 ppm acetone (1597 mg/m³) resulted in a statistically significant reduction in fetal weight and a slight but statistically significant increase in the percent incidence of late resorptions. The latter, however, did not affect the number of mean live fetuses per litter. The incidence of malformations was not increased at any exposure level.

3.2.5 Reference Dose/Concentration

Subchronic and chronic inhalation RfCs have not been derived for acetone (EPA, 1995).

3.3 OTHER ROUTES OF EXPOSURE

3.3.1 Acute Toxicity

3.3.1.1 Human

Intravenous administration of 200 mL of a 0.5% solution of acetone in saline over 2 hours to healthy and diabetic subjects resulted in a small decrease in blood pressure and slight transient drowsiness (Koehler et al., 1941).

In reviewing the available data, Morgott (1993) concluded that acetone is neither a skin irritant nor a contact allergen; however, prolonged or repeated dermal exposure may defat the skin and produce dermatitis (Krasavage et al., 1982). Direct contact with the eyes may produce irritation and corneal injury (Morgott, 1993). Vapor concentrations of 300 ppm may produce slight eye irritation in some individuals (Nelson et al., 1943).

3.3.1.2 Animal

Intravenous injections of 1576 and 4000 mg/kg were lethal to rabbits and mice, respectively, and a dose of 5500 mg/kg was the estimated intravenous LD₅₀ in rats (RTECS, 1995). Intravenous doses of 4 mL/kg (3164 mg/kg) and 6-8 mL/kg (4746-6328 mg/kg) were lethal to rats and rabbits, respectively, and an intramuscular dose of 5 mL/kg (3955 mg/kg) produced central nervous system depression in rabbits (Walton et al., 1928).

Intraperitoneal doses of 500 mg/kg and 8000 mg/kg were lethal to rats and dogs, respectively (Sanderson, 1959; RTECS, 1995), and an intraperitoneal LD₅₀ of 1297 mg/kg was reported for mice (Krasavage et al., 1983). A subcutaneous dose of 5 g/kg was lethal to dogs and guinea pigs (Krasavage et al., 1983).

Application of 395 or 500 mg acetone to the skin of rabbits for up to 24 hours caused only mild irritation; however, 20 mL/kg (15.8 g/kg) was lethal (RTECS, 1995). A dermal LD₅₀ of 20,000 mg/kg has been reported for rabbits (Krasavage et al., 1983), and the dermal LD₅₀ for guinea pigs was reported to be >9400 mg/kg (RTECS, 1995).

Percutaneous or subcutaneous exposure to acetone induced the formation of cataracts in guinea pigs; however, similar effects were not observed in rabbits (Rengstorff et al., 1972; 1975; Rengstorff and Khafagy, 1985).

Studies in animals have shown that when applied undiluted to the eyes and left in contact with the cornea for an extended period of time, acetone can cause ocular damage (Morgott, 1993). Application of 20 mg to the eye of rabbits caused moderate to severe corneal injury (RTECS, 1995).

3.3.2 Subchronic Toxicity

3.3.2.1 Human

Repeated exposure to 25-920 ppm acetone (6-2226 mg/m³) may result in chronic conjunctivitis (Verschueren, 1983).

3.3.2.2 Animal

Mice treated subcutaneously with 400 mg/kg/day acetone, 5 days/week for 15 weeks, showed no evidence of neurological dysfunction relative to control animals (Misumi and Nagano, 1984).

3.3.3 Chronic Toxicity

3.3.3.1 Human

Information was not found in the available literature on the chronic toxicity of acetone in humans by other routes of exposure.

3.3.3.2 Animal

A study was conducted by Zakova et al. (1985) in which acetone (0.2 mL) was applied to the shaved back of 6-week-old male and female CF1 mice once per week until the animals were 2 years old. Acetone had no effect on survival rates, and local irritation was seen at the application site in only 6% of the test animals.

3.3.4 Developmental and Reproductive Toxicity

3.3.4.1 Human

Information was not found in the available literature on the developmental/reproductive effects of acetone in humans by other routes of exposure.

3.3.4.2 Animal

Using an in vitro rat whole embryo culture system, Kitchin and Ebron (1984) found that acetone concentrations of >=0.5% when added to the culture medium caused structurally abnormal embryos and a high rate of embryo mortality. Using a similar test system, Schmid (1985) reported that acetone concentrations of >=0.6% were embryotoxic and 3% inhibited growth and differentiation. No evidence of teratogenicity was seen in chick embryos when 39 or 78 mg of acetone was injected into the yolk sacs prior to incubation (McLauglin et al., 1964). Similarly, Korhonen et al. (1983) reported that 5 mL acetone injected into chicken eggs did not increase the percentage of malformations in the embryos that failed to survive.

3.4 TARGET ORGANS/CRITICAL EFFECTS

3.4.1 Oral Exposures

Information on target organs affected by long-term oral exposures is available only from animal studies.

3.4.1.1 Primary target organs

1. Kidney. Renal tubular degeneration and hyaline droplet accumulation in rats following subchronic exposure conditions.
2. Liver. Increase in absolute and relative liver weight in rats following subchronic exposure conditions.

3.4.1.2 Other target organs

1. Blood. Changes in red blood cells in rats following subchronic exposures.

3.4.2 Inhalation Exposures

3.4.2.1 Primary target organs

1. Nervous system. In humans, acute exposures to acetone produce central nervous system effects ranging from subtle neurobehavioral changes to narcosis depending on the concentration and length of exposure. Chronic exposures to low concentrations have been associated with transient irritant effects but no systemic disorders.

3.4.2.2 Other target organs

1. Respiratory tract. Acute exposures produce eye and respiratory tract irritation in humans and animals.

4. CARCINOGENICITY

4.1 ORAL EXPOSURES

4.1.1 Human

No information was found in the available literature on the potential carcinogenicity of acetone in humans following oral exposures.

4.1.2 Animal

Acetone has not been tested in a 2-year rodent bioassay for carcinogenicity; however, in vitro tests for mutagenicity, chromosome damage, and DNA interaction indicate that acetone is not genotoxic except under severe conditions (Morgott, 1993).

4.2 INHALATION EXPOSURES

4.2.1 Human

Ott et al. (1983a, 1983b) examined the mortality rates and clinical chemistry results for 948 cellulose fiber production plant employees who were exposed to 380, 770, or 1070 ppm acetone (median TWA) over a span of 23 years. There were no statistical differences from control values in total malignant neoplasms.

4.2.2 Animal

Acetone has not been tested in a 2-year rodent bioassay for carcinogenicity; however, in vitro tests for mutagenicity, chromosome damage, and DNA interaction indicate that acetone is not genotoxic except under severe conditions (Morgott, 1993)

4.3 OTHER ROUTES OF EXPOSURE

The carcinogenicity of acetone was evaluated in a mouse skin-painting study in which 0.1 mL was applied to the skin of female ICR/Ha Swiss mice three times a week for one year (Van Duuren et al., 1971). Tumor incidence was reported to be similar to the background incidence in untreated mice.

In a study conducted by Zakova et al. (1985), 0.2 mL acetone was applied to the shaved back of 6-week-old male and female CF1 mice once per week until the animals were 2 years old. No skin tumors were seen except for a subcutaneous fibrosarcoma which was not considered treatment related. The occurrence and frequency of systemic tumors (primarily those of the lymphoreticular and hematopoietic systems) was reported to be similar to background rates for this strain of mice. Negative results for tumorigenicity of acetone in mice have also been reported by Ward et al. (1986), Peristianis et al. (1988), and Iverson et al. (1991).

4.4 EPA WEIGHT-OF-EVIDENCE

Classification--D; not classifiable as to human carcinogenicity (EPA, 1995).

Basis--Lack of data concerning carcinogenicity in humans or animals (EPA, 1995). Studies reviewed by EPA (1995) indicate that acetone gave negative responses in mutagenicity assays using microorganisms and mouse lymphoma cells, in cell transformation assays, in sister chromatid exchange assays, and in DNA binding assays; the only reported positive response was for chromosomal aberrations. Acetone also gave a negative response in both in vitro and in vivo micronucleus tests (Fritzenschaf et al., 1993).

VERIFICATION DATE: 12/06/89.

4.5 CARCINOGENICITY SLOPE FACTORS

Slope factors have not been calculated for acetone (EPA, 1995).

5. REFERENCES

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

ATSDR (Agency for Toxic Substances and Disease Registry). 1994. Toxicological Profile for Acetone, U.S. Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA, 157 pp.

Axelsson, G., C. Luetz and R. Rylander. 1984. Exposure to solvents and outcome of pregnancy in university laboratory employees. Br. J. Ind. Med. 41:305-312. (Cited in ATSDR, 1994)

Brown, E. M. and W. R. Hewitt. 1984. Dose-response relationships in ketone-induced potentiation of chloroform hepato- and nephrotoxicity. Toxicol. Appl. Pharmacol. 76:437-453. (Cited in ATSDR, 1994)

Bruckner, J. V. and R. G. Peterson. 1981. Evaluation of toluene and acetone inhalant abuse. II. Model development and toxicology. Toxicol. Appl. Pharmacol. 61:302-312. (Cited in EPA, 1988)

De Ceaurriz, J., J. C. Micillino, B. Marignac, et al. 1984. Quantitative evaluation of sensory irritating and neurobehavioral properties of aliphatic ketones in mice. Food Chem. Toxicol. 22:545-549. (Cited in Morgott, 1993)

Dick, R. B, J. V. Setzer, B. J. Taylor, et al. 1989. Neurobehavioral effects of short duration exposure to acetone and methyl ethyl ketone. Br. J. Ind. Med. 46:111-121. (Cited in ATSDR, 1994)

Dietz, D. D., J. R. Leininger, E. J. Rauckman, et al. 1991. Toxicity studies of acetone administered in the drinking water of rodents. Fundam. Appl. Toxicol. 17:347-360. (Cited in ATSDR, 1994; Morgott, 1993)

EHRT. 1987. Screening of priority chemicals for reproductive hazards: Benzethonium chloride (CAS No. 121-54-0); 3-ethoxy-1-propanol (CAS No. 111-35-3): acetone (CAS No. 67-64-1), Environmental Health Research and Testing, Inc., Cincinnati, OH. NTIS PB89-139083. (Cited in ATSDR, 1994)

EPA (U.S. Environmental Protection Agency). 1980. Acetone: Hazard profile, Environmental Criteria and Assessment Office, Office of Research and Development, Cincinnati, OH.

EPA (U.S. Environmental Protection Agency). 1984. Health Effects Assessment for Acetone, Environmental Criteria and Assessment Office, Office of Research and Development, Cincinnati, OH.

EPA (U.S. Environmental Protection Agency). 1986. Ninety-day Gavage Study in Albino Rats Using Acetone, Office of Solid Waste and Emergency Response, Washington, D.C. (Cited in EPA, 1995)

EPA (U.S. Environmental Protection Agency). 1994. Health Effects Summary Tables, FY 1994, Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH, for the Office of Emergency and Remedial Response. Washington, DC.

EPA (U.S. Environmental Protection Agency). 1995. Integrated Risk Information System (IRIS), Acetone, Online file, updated 08/02/93, retrieved March 22, 1995, Office of Health and Environmental Assessment, Cincinnati, OH.

Fritzenschaf, H., M. Kohlpoth, B. Rusche and D. Schiffmann. 1993. Testing of known carcinogens and noncarcinogens in the Syrian hamster embryo (SHE) micronucleus test in vitro: Correlations with in vivo micronucleus formation and cell transformation. Mutat. Res. 319:47-53.

Garcia, C. R., I. Geller and H. L. Kaplan. 1978. Effects of ketones on lever-pressing behavior of rats. Proc. West Pharmacol. Soc. 21:433-438. (Cited in ATSDR, 1994)

Geller, I., H. Gause, H. Kaplan and R. J. Hartmann. 1979. 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.

Gitelson, S., A. Werczberger and J. R. Herman. 1966. Coma and hyperglycemia following drinking of acetone. Diabetes 15:810-811. (Cited in ATSDR, 1994)

Glowa J. R. and P. B. Dews. 1987. Behavioral toxicology of volatile organic solvents. IV. Comparisons of the rate-decreasing effects of acetone, ethyl acetate, methyl ethyl ketone, toluene, and carbon disulfide on schedule-controlled behavior of mice. J. Am. College Toxicol. 6:461-469. (Cited in ATSDR, 1994).

Goldberg, M. E., H. E. Johnson, U. C. Pozzani and H. F. Smyth, Jr. 1964. Effects of repeated inhalation of vapors of industrial solvent on animal behavior. Am. Ind. Hyg. Assoc. J. 25:369-375. (As cited in NIOSH, 1978)

Grampella, C., G. Catenacci, L. Garavaglia and S. Tringali. 1987. Health surveillance in workers exposed to acetone. In: Proc. VII Int. Symp. Occup. Health Prod. Artif. Organic Fibres. Wolfheze, Holland. (Cited in Morgott, 1993)

Grasso, P., M. Sharratt, D. M. Davies, and D. Irvine. 1984. Neurophysiological and psychological disorders and occupational exposure to organic solvents. Fd. Chem. Toxicol. 22:819-852. (Cited in Martin 1986)

Hazardous Substances Database (HSDB). 1995. Online file, available through the National Library of Medicine's MEDLARS system, National Library of Medicine.

Inoue, T. 1983. Acetone. In: Encyclopaedia of Occupational Health and Safety, 3rd rev. ed., L. Parmeggiani, ed. International Labor Office, Geneva. pp. 38-39.

Iverson, O. H. 1991. The skin tumorigenic and carcinogenic effects of different doses, number of dose fractions and concentrations of 7,12-dimethylbenz[a]anthracene in acetone applied on hairless mice epidermis. Possible implications for human carcinogenesis. Carcinogenesis 12:493-502. (Cited in Morgott, 1993)

Kimura, E. T., D. M. Ebert and P. W. Dodge. 1971. Acute toxicity and limits of solvent residue for sixteen organic solvents. Toxicol. Appl. Pharmacol. 19:699-704. (Cited in Morgott, 1993)

Kitchin, K. T. and M. T. Ebron. 1984. Further development of rodent whole embryo culture: solvent toxicity and water insoluble compound delivery system. Toxicology 30:45-57. (Cited in Morgott, 1993)

Koehler, A. E., E. Windsor and E. Hill. 1941. Acetone and acetoacetic acid studies in man. J. Biol. Chem. 140:811-825. (Cited in Morgott, 1993)

Korhonen, A. K. Hemminki and H. Vainio. 1983. Embryotoxic effects of acrolein, methacrylates, guanidines and resorcinol on three day chicken embryos. Acta Pharmacol. Toxicol. 52:95-99. (Cited in Morgott, 1993)

Krasavage, W. J., J. L. O'Donoghue and G. D. Divincenzo. 1982. Acetone. In: Patty's Industrial Hygiene and Toxicology, 3rd rev. ed., vol. 2c., G. D. Clayton and F. E. Clayton, eds. Wiley Interscience, New York. pp. 4720-4727.

Kumai, M., A. Koizumi, K. Saito, et al. 1983. A nationwide survey on organic solvent components in various solvent products: Part 2. Heterogeneous products such as paints, inks, and adhesives. Ind. Health 21:185-197.

Ladefoged, O., U. Hass and L. Simonsen. 1989. Neurophysiological and behavioral effects of combined exposure to 2,5-hexanedione and acetone or ethanol in rats. Pharmacol. Toxicol. 65:372-375. (Cited in ATSDR, 1994)

Larsen, J. J., M. Lykkegaard and O. Ladefoged. 1991. Infertility in rats induced by 2,4-hexanedione in combination with acetone. Pharmacol. Toxicol. 69:43-46. (Cited in ATSDR, 1994).

Mast, T. J., J. J. Evanoff, R. L. Rommereim, et al. 1988. Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats, National Toxicology Program, Contract DE-AC06-76RLO 1830. Pacific Northwest Laboratory, Battelle Memorial Institute. (Cited in Morgott, 1993)

Mashbitz, L. M., R. M. Sklianskaya and F. I. Urieva. 1936. The relative toxicity of acetone, methylalcohol and their mixtures: II. Their action on white mice. J. Ind. Hyg. Toxicol. 18:117-122. (Cited in ATSDR, 1994)

Matsushita, T., A. Yoshimune, A. Inoue, et al. 1969a. Experimental studies for determining the MAC value of acetone. 2. Biological reaction time in the "one-day exposure" to acetone. Sangyo Igaku 11:477-484. [Japanese] (Cited in ATSDR, 1994)

Matsushita, T., E. Goshima, H. Miyagaki, et al. 1969b. Experimental studies for determining the MAC value of acetone. 2. Biological reaction time in the "six-day exposure" to acetone. Sangyo Igaku 11:505-511. [Japanese] (Cited in ATSDR, 1994)

McLaughlin, J., J-P. Marliac, M. J. Verrett, et al. 1964. Toxicity of fourteen volatile chemicals as measured by the chick embryo method. Am. Ind. Hyg. J. 25:282-284. (Cited in Morgott, 1993)

Misumi, J. and M. Nagano. 1984. Neurophysiological studies on the relation between the structural properties and neurotoxicity of aliphatic hydrocarbon compounds in rats. Brit. J. Ind. Med. 41:526-532. (Cited in Morgott, 1993)

Mizunuma, K., T. Yasugi, T. Kawai, et al. 1993. Exposure-excretion relationship of styrene and acetone in factory workers: a comparison of a lipophilic solvent and a hydrophilic solvent. Arch. Environ. Contam. Toxicol. 25:129-133.

Morgott, D. A. 1993. Acetone. In: Patty's Industrial Hygiene and Toxicology, 4th ed., vol. 2, Part A, G.D. Clayton and F.E. Clayton, eds. John Wiley & Sons, Inc., NY

Nelson, K. W., J. F. Ege, Jr., M. Ross, et al. 1943. Sensory response to certain industrial solvent vapors. J. Ind. Hygiene Toxicol. 25:282-285. (Cited in Morgott, 1993)

NTP (National Toxicology Program). 1991. Toxicity Studies of Acetone in F344/N Rats and B6C3F₁ Mice (Drinking Water Studies), NTP TOX 3 (NIH Publ. No. 91-3122), National Toxicology Program, Research Triangle Park, NC.

Oglesby, F. L., J. L. Williams and D. W. Fassett. 1949. Eighteen-year experience with aceton. Paper presented at the Annual Meeting of the American Industrial Hygiene Association, Detroit, MI. (Cited in Morgott, 1993)

Ott, M. G., L. K. Story, B. B. Holder, et al. 1983a. Health evaluation of employees occupationally exposed to methylene chloride: Mortality. Scand. J. Work Environ. Health 9(Suppl. 1): 8-16. (Cited in Morgott, 1993)

Ott, M. G., L. K. Story, B. B. Holder, et al. 1983b. Health evaluation of employees occupationally exposed to methylene chloride: Clinical laboratory evaluation. Scand. J. Work Environ. Health 9(Suppl. 1): 17-25. (Cited in Morgott, 1993)

Peristianis, G. C., S. M. A. Doak, P. N. Cole, et al. 1988. Two-year carcinogenicity study of three aromatic epoxy resins applied cutaneously to CF1 mice. Food Chem. Toxicol. 26:611-624. (Cited in Morgott, 1993)

Pozzani, U. C., C. S. Weil and C. P. Carpenter. 1959. The toxicological basis for threshold limit values: 5. The experimental inhalation of vapor mixtures by rats, with notes upon the relationship between single dose inhalation and single dose oral data. Am. Ind. Hyg. Assoc. J. 20:364-369. (Cited in Morgott, 1993)

Raleigh, R. L. and W. A. McGee. 1972. Effects of short, high-concentration exposures to acetone as determined by observation in the work area. J. Occup. Med. 14:607-610. (Cited in EPA, 1988)

Rengstorff, R. H., J. P. Petrali and V. M. Sim. 1972. Cataracts induced in guinea pigs by acetone, cyclohexanone, and dimethyl sulfoxide. Am. J. Optom Physiol. Optics 49:308-319. (Cited in ATSDR, 1994)

Rengstorff, R. H., J. P. Petrali and V. M. Sim. 1975. Attempt to induce cataracts induced in rabbits by cutaneous application of acetone. Am. J. Optom. Physiol. Optics 53:41-42. (Cited in ATSDR, 1994)

Rengstorff, R. H. and H. I. Khafagy. 1985. Cutaneous acetone depresses aqueous humor ascorbate in guinea pigs. Arch. Toxicol. 58:64-66. (Cited in NTP, 1991)

Ross, D. J. 1973. Acute acetone intoxication involving 8 male workers. Ann. Occup. Hyg. 16:73-75. (Cited in ATSDR, 1994)

RTECS (Registry of Toxic Effects of Chemical Substances). 1995. National Institute of Occupational Safety and Health (NIOSH) online database available through the National Library of Medicine's MEDLARS system, Washington, D.C.

Sanderson, D. M. 1959. A note on glycerol formal as a solvent in toxicity testing. J. Pharm. Pharmacol. 11:150-156. (cited in Krasavage et al., 1983

Sax, N. I. 1984. Dangerous Properties of Industrial Materials, 6th ed. New York: Van Nostrand Reinhold Co.

Schmid, B. P. 1985. Xenobiotic influences on embryonic differentiation, growth and morphology in vitro. Xenobiotica 15:719-726. (Cited in Morgott, 1993)

Specht, H., J. W. Miller, P. J. Valaer, et al. 1939. Acute response of guinea pigs to the inhalation of ketone vapors, NIH bulletin No. 176, Federal Security Agency, Public Health Service, National Institute of Health. (As cited in NIOSH, 1978; ATSDR, 1994)

Spencer, P. S., M. C. Bischoff and H. H. Schaumburg. 1978. On the specific molecular configuration of neurotoxic aliphatic hexacarbon compounds causing central-peripheral distal axonopathy. Toxicol. Appl. Pharmacol. 44:17-28. (Cited in Morgott, 1993)

Stewart, R. D., C. L. Hake, A. Wu, et al. 1975. Acetone: Development of a Biologic Standard for the Industrial Worker by Breath Analysis, NTIS PB82-172917, National Institute for Occupational Safety and Health. (Cited in ATSDR, 1994)

Tada, O., K. Nakaaki and S. Fukabori. 1972. Experimental study on acetone and methyl ethyl ketone concentrations in urine and expired air after exposure to those vapors. Rodo Kagaku 48: 305-331. (Cited in Krasavage et al., 1982).

U.S. Air Force. 1989. Acetone. In: The Installation Restoration Program Toxicology Guide, vol. 3, Wright-Patterson Air Force Base, OH. pp. 40-1 to 40-29.

Van Duuren, B. L., A. Sivak, C. Katz and S. Melchionne. 1971. Cigarette smoke carcinogenesis: Importance of tumor promoters. J. Nat. Cancer Inst. 47:235-240 (Cited in USAF, 1989)

Verschueren, K. 1983. Handbook of Environmental Data on Organic Chemicals, 2nd ed., Van Nostrand Reinhold Company, New York. pp. 147-150.

Walton, D. C., E. F. Kehr and A. S. Loevenhart. 1928. A comparison of the pharmacological action of diacetone alcohol and acetone. J. Pharmacol. Exp. Ther. 33:175-183. (cited in Krasavage et al., 1983)

Ward, J. M., R. Quander, D. Devor, et al. 1986. Pathology of aging female SENCAR mice used as controls in skin two-stage carcinogenesis studies. Environ. Health Perspect. 68:81-89. (Cited in Morgott, 1993)

Widmark, E. M. P. 1919. Studies on the concentration of indifferent narcotics in blood and tissue. Acta Med. Scand. 52:87-164. (Cited in Morgott, 1993)

Wigaeus, E., S. Holm and I. Astrand. 1981. Exposure to acetone. Uptake and elimination in man. Scand. J. Work Environ. Health 7:84-94. (Cited in EPA, 1988)

Zakova, N., F. Zak, E. Froehlich and R. Hess. 1985. Evaluation of skin carcinogenicity of technical 2,2-bis(p-glycidyloxyphenyl)-propane in CF1 mice. Food and Chem. Toxic. 23:1081-1089. Retrieve Toxicity Profiles Condensed Version

Last Updated 8/29/97