EPA-540/1-86-016
Office of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
vvEPA
HEALTH EFFECTS ASSESSMENT
FOR ACETONE
-------
EPA/540/1-86-016
September 1984
HEALTH EFFECTS ASSESSMENT
FOR ACETONE
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
-------
DISCLAIMER
This report has been funded wholly or In part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and It has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment or recommendation for use.
11
-------
PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with acetone.
All estimates of acceptable Intakes and carcinogenic potency presented 1n
this document should be considered as preliminary and reflect limited
resources allocated to this project. Pertinent toxlcologlc and
environmental data were located through on-line literature searches of the
Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data
bases. The basic literature searched supporting this document 1s current up
to September, 1984. Secondary sources of Information have also been relied
upon 1n the preparation of this report and represent large-scale health
assessment efforts that entail extensive peer and Agency review. The
following Office of Health and Environmental Assessment (OHEA) sources have
been extensively utilized:
U.S. EPA. 1981. Criteria Document for Acetone. Environmental
Criteria and Assessment Office, Cincinnati, OH. Internal Draft.
U.S. EPA. 1983b. Disposition of Comments on Criteria Document for
Acetone. Environmental Criteria and Assessment Office, Cincinnati,
OH. Internal Draft.
The Intent In these assessments 1s to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger.
uncertainty factors were employed when the variable data were limited 1n
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the Interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer 1s not the endpolnt of concern).
The first, the AIS or acceptable Intake subchronlc, 1s an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval (I.e., for an Interval that
does not constitute a significant portion of the Hfespan). This type of
exposure estimate has not been extensively used or rigorously defined, as
previous risk assessment efforts have been primarily directed towards
exposures from toxicants 1n ambient air or water where lifetime exposure 1s
assumed. Animal data used for AIS estimates generally Include exposures
with durations of 30-90 days. Subchronlc human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
The AIC, acceptable Intake chronic, 1s similar In concept to the ADI
(acceptable dally Intake). It Is an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the Hfespan [see U.S. EPA (1980) for a discussion of
this concept]. The AIC 1s route specific and estimates acceptable exposure
for a given route with the Implicit assumption that exposure by other routes
1s Insignificant.
111
-------
Composite scores (CSs) for noncardnogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development 1s explained 1n U.S. EPA (1983b).
For compounds for which there 1s sufficient evidence of carclnogenlclty,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980). Since cancer 1s a
process that 1s not characterized by a threshold, any exposure contributes
an Increment of risk. Consequently, derivation of AIS and AIC values would
be Inappropriate. For carcinogens, q-|*s have been computed based on oral
and Inhalation data 1f available.
1v
-------
ABSTRACT
In order to place the risk assessment evaluation 1n proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation and use of the quantitative estimates presented.
The AIC for acetone, 209.6 mg/day, 1s based on a subchronlc (8-week)
animal exposure study showing reversible changes following exposure to
19,000 ppm acetone. Although data are extremely limited, fragmentary human
data at similar exposure concentrations Indicate no adverse effects. In
addition, this AIC 1s below that which could be calculated from the most
conservative occupational exposure guidelines (NIOSH, 1978). This estimate
may be conservative and reflects the limited data base. Data were Inade-
quate to estimate an AIS or AIC for oral exposure and were also Insufficient
for derivation of a CS.
-------
ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was the Project
Officer. The final documents 1n this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of Air Quality Planning and Standards
Office of Solid Haste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
-------
TABLE OF CONTENTS
1.
2.
3.
4.
5.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1.
2.2.
ORAL
INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1.
3.2.
3.3.
3.4.
SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation
CHRONIC
3.2.1. Oral
3.2.2. Inhalation
TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.3.1. Oral
3.3.2. Inhalation
TOXICANT INTERACTIONS
CARCINOGENICITY
4.1.
4.2.
4.3.
4.4.
HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
OTHER RELEVANT DATA
WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
Page
1
3
... 3
... 3
5
5
... 5
... 5
... 5
... 5
5
. , . 6
... 6
6
6
... 7
7
... 7
7
, , . 7
... 7
... 7
... 7
... 7
... 9
-------
TABLE OF CONTENTS (cont.)
Page
6. RISK ASSESSMENT 10
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 10
6.1.1. Oral 10
6.1.2. Inhalation 10
6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 11
6.2.1. Oral 11
6.2.2. Inhalation 11
6.3. CARCINOGENIC POTENCY (q-|*) 12
6.3.1. Oral 12
6.3.2. Inhalation 12
7. REFERENCES 13
APPENDIX: Summary Table for Acetone 21
-------
LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
BCF B1oconcentrat1on factor
CAS Chemical Abstract Service
CS Composite score
DNA Deoxyrlbonuclelc acid
1050 Dose lethal to 50% of recipients
NOAEL No-observed-adverse-effect level
ppm Parts per million
STEL Short-term exposure limit
TLV Threshold limit value
TWA Time-weighted average
1x
-------
1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties and environmental fate of
acetone (CAS No. 67-64-1} are as follows:
Molecular weight:
Chemical class:
Vapor pressure:
Water solubility:
Log octanol/water
partition coefficient;
BCF:
Half-lives 1n A1r:
Water:
58.08
aliphatic ketone
185.95 mm Hg at 20°C
mlsdble with water
-0.24
0.69 1n haddock
muscle (Melanoqrammus
aeglef1nus)
0.12 (estimated)
14 hours
10 hours to 9 days
U.S. EPA, 1981
U.S. EPA, 1981
U.S. EPA, 1981
U.S. EPA, 1981
Graedel, 1978
U.S. EPA, 1981
The BCF value of 0.12 has been estimated from the equation of Veith et
al. (1979) and the log octanol/water partition coefficient given above.
The value for the half-life of acetone In the atmosphere 1s based on Its
photochemical reaction and the rate constant for the photochemical reaction
given by Graedel (1978). The half-life of acetone 1n water 1s based on Its
evaporation rate from quiescent to different aerated conditions. The bio-
degradation half-life may be comparable to Its evaporation half-life under
certain conditions; however, blodegradatlon has not been considered In
estimating the aquatic half-life of acetone because of the lack of available
rate constant data.
-1-
-------
The half-life of acetone 1n soil could not be located In the literature
searched; however, evaporation 1s expected to be the predominant loss mecha-
nism from the soil surface. By analogy with the blodegradatlon studies of
acetone 1n other media (U.S. EPA, 1981), It Is likely that It will undergo
significant blodegradatlon 1n soils as well. The undecomposed acetone Is
expected to leach from soil because of Its high water solubility and
expected weak sorptlon on soils. The detection of acetone in both soil
leachate and groundwater 1s evidence for Us soil Teachability (U.S. EPA,
1981).
-2-
-------
2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Although absorption factors were not reported, several studies Indicate
that acetone 1s readily absorbed through the gastrointestinal tract 1n
humans and animals.
Schwartz (1898) administered acetone either orally or subcutaneously to
dogs. For both routes of exposure, 59-76% of the administered dose was
eliminated through expired air, while 1.5-4.7% was excreted 1n the urine.
Haggard et al. (1944), Parmegg1an1 and Sassl (1954), and Price and
RHtenberg (1950) also reported that orally administered acetone was elimi-
nated through expired air and in the urine.
2.2. INHALATION
Numerous reports Indicate that acetone is absorbed through the pulmonary
route of exposure. Dalhamn et al. (1968) demonstrated that 60% of the
Inhaled dose of acetone (~1 mg in cigarette smoke) was absorbed by. humans
within 2 seconds of contact. Haggard et al. (1944) reported that the
absorption of acetone through inhalation in rats is rapid and dose-related,
reaching steady-state after 2 days of continuous exposure. Similar results
were obtained with volunteers; however, steady-state was not achieved
because these Individuals were exposed for only 8 hours. Furthermore,
greater absorption of acetone was observed 1n the volunteers who exercised
during Inhalation.
In an experiment similar to that of Haggard et al. (1944), DIVIncenzo et
al. (1973) determined that light exercise (a cycle of jogging for 5 minutes
followed by 10 minutes of rest) approximately doubled the postexposure
levels of acetone in the expired breath of volunteers. Wlgaeus et al.
-3-
-------
(1981) also reported that the absorption of acetone through Inhalation In
volunteers Increased with exercise, but added further that the relative
uptake (39-52%) was not affected by the workload.
-4-
-------
3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Very little Information regarding the subchronlc toxldty
of orally administered acetone was located 1n the available literature.
Sollman (1921) exposed three rats to 2.5% acetone In drinking water for 18
weeks. Upon termination of the experiment, the animals were found to be
"practically normal," experiencing only weight loss, which might have been
due to decreased food consumption. No other endpolnts were examined or
reported.
3.1.2. Inhalation. Information regarding the subchronlc toxldty of
Inhaled acetone Is also limited. Bruckner and Peterson (1981) exposed rats
to vapors of acetone at levels of either 0 or 19,000 ppm for 3 hours/day, 5
days/week for 8 weeks. Groups of four rats were killed and examined at 2, 4
and 8 weeks throughout exposure and at 2 weeks postexposure. Narcosis was
seen 1n animals exposed to acetone. These animals, however, had no changes
1n clinical chemistry variables or hlstologlcal changes 1n the liver, brain,
kidneys, lungs or heart regardless of when they were examined. Slight
decreases 1n organ weights and body weights were observed In rats killed
during exposure but not 1n rats killed 2 weeks postexposure.
3.2. CHRONIC
3.2.1. Oral. Pertinent data regarding the chronic toxldty of orally
administered acetone were not located 1n the available literature.
3.2.2. Inhalation. In two other occupational exposure studies, workers
exposed to vapors of acetone at either 19-920 ppm (Parmegglanl and Sassl,
1954) or >750 ppm (Raleigh and McGee, 1972) complained of Irritation of the
mucosal membranes, Including conjunctivitis, pharyngitis, Inflammatory
bronchitis and gastroduodenltls.
-5-
-------
Oglesby et al. (1949) examined the physical condition, and hematologlcal
and urologlcal variables 1n 800 men exposed occupatlonally to vapors of
acetone (600-2150 ppm). These men were examined once a year from 1931 to
1948. There were no statistically significant differences between these men
and a group of 800 controls with respect to any of the variables measured,
though transient eye and nose irritation was experienced by some of the
exposed workers. This study Indicates that exposure to <2150 ppm acetone
for <8 hours/day produces no significant toxic effects.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenlcity of Ingested
acetone were not located in the available literature; however, acetone 1s
known to cross the placenta (Dowty et al., 1975).
3.3.2. Inhalation. Pertinent data regarding the teratogenlcity of
Inhaled acetone were not located in the available literature.
3.4. TOXICANT INTERACTIONS
A number of studies indicate that acetone potentiates the hepatotoxlc
effects of carbon tetrachloride (Tralger and Plaa, 1973; Plaa et al., 1975,
1982; Folland et al., 1976), 1,1,2-tr1chloroethane and 1,1 ,l-tr1chloroethane
(Tralger and Plaa, 1973; Plaa et al., 1975; MacDonald et al., 1982), and
Br-CHCl and trichloroethane (Hewitt et al., 1983). Acetone was also
reported to antagonize semicarbaz1de-1nduced convulsions 1n rats (Kohli et
al., 1967), but had an additive effect upon LD™ In rats treated with
acetonltrile (Smyth et al., 1962).
Glatt et al. (1981) reported that acetone enhanced the mutagenic
activity of dlmethylnitrosamine 1n Iji vitro assays but not J_n vivo assays.
-6-
-------
4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent data regarding the cardnogenlcHy of Ingested
acetone were not located In the available literature.
4.1.2. Inhalation. Pertinent data regarding the cardnogenlcHy of
Inhaled acetone were not located 1n the available literature.
4.2. BIOASSAYS
4.2.1. Oral. Pertinent data regarding the cardnogenlcHy of orally
administered acetone were not located 1n the available literature.
4.2.2. Inhalation. Pertinent data regarding the cardnogenlcHy of
Inhaled acetone were not located 1n the available literature.
4.3. OTHER RELEVANT DATA
Acetone did not show mutagenlc activity when tested 1n microblal assay
systems (McCann et a!., 1975; Abbondandolo et a!., 1980; Maron et al., 1981;
Haellstrom et al., 1981) or 1n cell transformation systems (Freeman et al.,
1973; Rh1m et al., 1974; Quarles et al., 1979a,b). Furthermore, acetone
gave negative results In assays that tested for chromosomal aberrations and
sister chromatld exchange (Norppa et al., 1981; Norppa, 1981; Tates and
KMek, 1981), DNA cell binding (Kublnskl et al., 1981), point mutation 1n
mouse lymphoma cells (Amacher et al., 1980) and transfectlon (Vasavada and
Padayatty, 1981). In one study, however, acetone was reported to produce
chomosomal aberrations but not sister chromatld exchange (Kawachl et al.,
1980).
4.4. WEIGHT OF EVIDENCE
Pertinent data regarding the cardnogenlcHy of acetone In humans or 1n
experimental animals were not located 1n the available literature. The
evidence for the cardnogenlcHy of acetone In humans 1s appropriately
-7-
-------
designated as Inadequate. Using the scheme for the classification of the
cardnogenlcHy of chemicals to humans proposed by the Carcinogenic Assess-
ment Group of the U.S. EPA (Federal Register, 1984), acetone is most appro-
priately designated a Class D - Not Classified chemical.
-8-
-------
5. REGULATORY STANDARDS AND CRITERIA
ACGIH (1983) has recommended a TLV-TWA of 750 ppm and a STEL of 1000 ppm
for occupational exposure to acetone. These values were chosen to prevent
nose and eye Irritation (ACGIH, 1980). NIOSH (1978) has recommended a
criterion of 250 ppm for exposure to acetone 1n the workplace, while OSHA
has adopted 1000 ppm as a standard for occupational exposure to acetone
(Code of Federal Regulations, 1981).
-9-
-------
6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral. The only subchronlc oral study located 1n the available
literature was that of Sollman (1921). Data from this study cannot be used
to derive an AIS or a CS because small numbers of animals were used; there
was only one level of exposure; and hlstologlcal endpolnts were not examined
and control animals were not maintained.
6.1.2. Inhalation. Bruckner and Peterson (1981) reported that rats
experienced narcosis during the 3-hour exposure periods to 19,000 ppm
acetone. In addition, body weight was slightly decreased 1n rats during the
8 weeks of treatment; however, body weight returned to control values by 2
weeks after cessation of exposure (Bruckner and Peterson, 1981). A NOAEL of
19,000 ppm can be established on the basis of reversible changes In organ
and body weights 1n rats.
Using the- NOAEL of 19,000 ppm (45,134 mg/m3), the animal dose 1n
mg/kg/day can be calculated by assuming a rat breathes 0.26 mVday and
weighs 0.35 kg, and by expanding the exposure from a 3-hour, 5 days/week
Intermittent exposure to a continuous exposure as follows:
mg/kg/day = 45,134 mg/m3 x 0.26 mVday x
3/24 x 5/7 * 0.35 kg = 2994 mg/kg/day
To calculate the AIS, this animal dose Is multiplied by the assumed
average human body weight of 70 kg and divided by an uncertainty factor of
100 (a factor 10 for converting an animal NOAEL to a human NOAEL and another
factor of 10 to protect the more sensitive Individuals of a population).
The AIS thus derived for acetone Is 2096 mg/day.
-10-
-------
Although exposure duration was only 3 hours/day, the extrapolation to a
24-hour day, 7 days/week exposure actually reduced the exposure concentra-
tion by more than a factor of 10 before uncertainty factors were applied.
The extrapolation 1s acceptable because this compound does not accumulate In
tissues, Including fat, and H 1s rapidly excreted In expired air and 1n
urine. Furthermore, there appear to be no major systemic effects other than
narcosis even at unusually high exposure levels. The estimate of an AIS for
Inhalation 1n mg/kg Implicitly assumes that the exposure will be spread
uniformly over a day.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral. Data are Insufficient to calculate an AIC for chronic oral
1ngest1on of acetone. Data from which a CS for oral exposure to acetone can
be calculated have not been located 1n the available literature.
6.2.2. Inhalation. The study by Oglesby et al. (1949) suggested a NOAEL
at <21,500 ppm for workers exposed to acetone, but the lack of properly
matched controls and uncertainties about levels of exposure preclude the use
of this study 1n quantitative risk assessment.
An Interim chronic Inhalation AOI can be derived from the Interim sub-
chronic Inhalation ADI of 2096 mg/day by applying an additional uncertainty
factor of 10 to convert subchronlc to chronic exposure. This results 1n an
AIC of 209.6 mg/day for a 70 kg human. This estimate 1s 1n the same range,
but more conservative than an estimate that could be derived using the most
conservative criterion for occupational exposure [NIOSH, 1978 (250 ppm)].
The estimate of an AIC for Inhalation In units of mg/day Implicitly assumes
that the exposure will be uniformly spread over the day. Data from which a
CS for Inhalation exposure to acetone can be calculated have not been
located 1n the available literature.
-11-
-------
6.3. CARCINOGENIC POTENCY (q.,*)
6.3.1. Oral. Data are Insufficient to calculate a q * for oral
exposure to acetone.
6.3.2. Inhalation. Data are Insufficient to calculate a q * for expo-
sure to acetone by Inhalation.
-12-
-------
7. REFERENCES
Abbondandolo, A., S. Bonattl, C. Corsl, et al. 1980. The use of solvents
1n mutagenicity testing. Mutat. Res. 79: 141-150. (Cited 1n U.S. EPA,
1983a)
ACGIH (American Conference of Governmental Industrial Hyglenists). 1980.
Documentation of the Threshold Limit Value, 4th edition. (Includes Supple-
mental Documentation, 1981, 1982, 1983.) Cincinnati, OH. p. 5-6.
ACGIH (American Conference of Governmental Industrial Hyglenists). 1983.
Threshold Limit Values for Chemical Substances and Physical Agents 1n the
Workroom Environment with Intended Changes for 1983-84. Cincinnati, OH.
p. 10.
Amacher, D.E., S.C. Palllet, G.N. Turner, V. Verne and D.S. Salsburg. 1980.
Point mutations at the thymldlne klnase locus in L5178Y mouse lymphoma
cells. 2. Test validation and Interpretation. Mutat. Res. 72: 447-474.
(Cited in U.S. EPA, 1983a)
Bruckner, J.V. and R.G. Peterson. 1981. Evaluation of toluene and acetone
inhalant abuse. II. Model development and toxicology. Toxicol. Appl.
Pharmacol. (In press) (Cited in U.S. EPA, 1983a)
Code of Federal Regulations. 1981. OSHA Safety and Health Standards. (29
CFR 1910.1000) p. 632.
-13-
-------
Dalhamn, T., M-L. Edfors and R. Rylander. 1968. Mouth absorption of
various compounds In cigarette smoke. Arch. Environ. Health. 16: 831-835.
(Cited In U.S. EPA, 1983a)
D1V1ncenzo, G.D., F.3. Yanno and B.O. Astm. 1973. Exposure of man and
dog to low concentrations of acetone vapor. Am. Ind. Hyg. J. 34: 329-336.
(Cited In U.S. EPA, 1983a)
Dowty, B.J., O.R. Carlisle and J.L. Laseter. 1975. New Orleans drinking
water sources tested by gas chromatography-mass spectrometry. Environ. Scl.
Techno!. 9(8): 762-765. (Cited In U.S. EPA, 1983a)
Federal Register. 1984. Environmental Protection Agency. Proposed guide-
lines for carcinogenic risk assessment. 49 FR 46294-46299.
Folland, D.S., W. Schaffner, H.E. 61nn, O.B. Crofford and D.R. McMurray.
1976. Carbon tetrachlorlde toxldty potentiated by Isopropyl alcohol.
Investigation of an Industrial outbreak. J. Am. Med. Assoc. 236(16):
1853-1856. (Cited 1n U.S. EPA, 1983a)
Freeman, A.E., E.K. Welsburger, J.H. Welsburger, R.G. Wolford, J.M. Maryak
and R.J. Huebner. 1973. Transformation of cell cultures as an Indication
of the carcinogenic potential of chemicals. J. Natl. Cancer Inst. 51(3):
799-808. (Cited In U.S. EPA, 1983a)
-14-
-------
Glatt, H., L. DeBalle and F. Oesch. 1981. Ethanol- or acetone-pretreatment
of mice strongly enhances the bacterial mutagenlclty of d1methyln1trosam1ne
1n assays mediated by liver subcellular fraction, but not 1n host-mediated
assays. Cardnogenesls. 2(10): 1057-1061.
Graedel, I.E. 1978. Chemical Compounds 1n the Atmosphere. Academic Press,
NY. p. 187.
Haellstroem, I., A. Sundvall, V. Rannug, R. Grafstrolm and C. Ramel. 1981.
The metabolism of drugs and carcinogens 1n Isolated subcellular fractions of
DrosophUa melanoqaster. I. Activation of vinyl chloride, 2-amlnoanthracene
and benzo(a)pyrene as measured by mutagenlc effects 1n Salmonella typhlmu-
rlum. Chem. B1ol. Interact. 34: 129-143. (Cited 1n U.S. EPA, 1983a)
Haggard, H.W.,. L.A. Greenburg and J.M. Turner. 1944. The physiological
principles governing the action of acetone together with determination of
toxldty. J. Ind. Hyg. Toxlcol. 26(5): 133-151. (Cited In U.S. EPA, 1983a)
Hewitt, W.R., E.M. Brown and G.L. Plaa. 1983. Acetone-Induced potentlatlon
of tMhalomethane toxldty In male rats. Toxlcol. Lett. 16(3-4): 285-296.
Kawachi, T., T. Yahagl, T. Kada, et al. 1980. Cooperative programme on
short-term assays for cardnogenldty 1n Japan. JJK Molecular and Cellular
Aspects of Carcinogen Screening Tests, R. Montesano, Ed. WHO, IARC, Lyon,
France, p. 323-330. (Cited In U.S. EPA, 1983a)
-15-
-------
Kohll, R.P., K. Klshor, P.R. Dua and R.C. Saxena. 1967. Antlconvulsant
activity of some carbonyl containing compounds. Indian J. Med. Res.
55(11): 1221-1225. {Cited 1n U.S. EPA, 1983a)
Kublnskl, H., G.E. Gutzke and Z.O. Kub1nsk1. 1981. DNA-cell-b1nd1ng (DC8)
assay for suspected carcinogens and mutagens. Mutat. Res. 89: 95-136.
(Cited In U.S. EPA, 1983a)
MacDonald, O.R., A.J. Gandolfl and I.G. S1pes. 1982. Acetone potentlatlon
of 1,1,2-trlchloroethane hepatotoxldty. Toxlcol. Lett. 13(1-2): 57-69.
McCann, 0., E. Choi, E. Yamasakl and B.N. Ames. 1975. Detection of carcin-
ogens as mutagens In the Salmonella/mlcrosome test: Assay of 300 chemicals.
Proc. Nat. Acad. Sd. 72(12): 5135-5139.
Maron, D., J. Katzenellenbogen and B.N. Ames. 1981. CompatabllHy of
organic solvents with the Salmonella/mlcrosome test. Mutat. Res. 88:
343-350. (Cited 1n U.S. EPA, 1983a)
NIOSH (National Institute of Occupational Safety and Health). 1978.
Criteria for a Recommended Standard...Occupational Exposure to Ketones.
OHEW(NIOSH) Publ. No. 78-173. p. 5-6. (Cited 1n ACGIH, 1980)
Norppa, H. 1981. The In vitro Induction of sister chromatld exchanges and
chromosome aberrations 1n human lymphocytes by styrene derivatives. Cardn-
ogene. 2: 237-242. (Cited 1n U.S. EPA, 1983a)
-16-
-------
Norppa, H., K. Hemlnkl, M. Sorsa and H. Valnes. 1981. Effect of monosub-
stHuted epoxldes on chromosome aberrations and SCE 1n cultured human
lymphocytes. Mutat. Res. 91: 243-250. (Cited In U.S. EPA, 1983a)
Oglesby, F.L., J.E. Williams, D.W. Fassett and J.H. Sterner. 1949. Eastman
Kodak Co., Rochester, NY, unpublished paper presented at the Annual Meeting
of the American Industrial Hygiene Association, Detroit. (Cited 1n U.S.
EPA, 1983a)
Parmegg1an1, L. and C. Sassl. 1954. Patologla professional da acetone:
Man1festaz1on1 cl1n1que, 1ndag1n1 negll amblentl d1 lavoro e Mcerche
flslopa tologlche. Med. Lavoro. 45(89): 431-468. (In Ital.; Eng. ab-
stract.) (CHed 1n U.S. EPA, 1983a)
Plaa, G.L., G.J. Tralger, G.K. Hanasono and H. W1tsch1. 1975. Effect of
alcohols on various forms of chemically Induced Hver Injury. In: Alcoholic
Liver Pathology, Proceedings of the International Symposium on Alcohol and
Drug Research, 3.M. Khanna, Y. Isreal and H. Kalant, Ed. Toronto, Canada:
Drug Addition Research Foundation, p. 225-244. (Cited 1n U.S. EPA, 1983a)
Plaa, G.L., W.R. Hewitt, P. Du Soulch, G. Callle and S. Lock. 1982.
Isopropanol and acetone potentlatlon of carbon tetrachlor1de-1nduced hepato-
toxldty: Single versus repetitive pretreatments in rats. J. Toxlcol.
Environ. Health. 9(2): 235-250.
-17-
-------
Price, T.D. and D. RHtenberg. 1950. The metabolism of acetone. I. Gross
aspects of catabollsm and excretion. J. B1ol. Chem. 185: 449-459. (Cited
1n U.S. EPA, 1983a)
Quarles, J.M., M.W. Sega, C.K. Schenley and W. L1j1nsky. 1979a. Transform-
ation of hamster fetal cells by nltrosated pesticides In a transplacental
assay. Cancer Res. 39: 4525-4533. (Cited In U.S. EPA, 1983a)
Quarles, J.M., M.W. Sega, C.K. Schenley and R.W. Tennant. 1979b. Rapid
screening for chemical carcinogens: transforming activity of selected
nltroso compounds 1n a transplacental host-mediated culture system. Nat.
Cancer Inst. Monogr. 51: 257-263. (Cited In U.S. EPA, 1983a)
Raleigh, R.L. and W.A. McGee. 1972. Effects of short, high-concentration
exposures to acetone as determined by observation 1n the work area. J-.
Occup. Med. 14(8): 607-610. (Cited 1n U.S. EPA, 1983a)
Rh1m, J.S., O.K. Park, E.K. Welsburger and 3.H. Welsburger. 1974. Evalua-
tion of an In vitro assay system for carcinogens based on prior Infection of
rodent cells with nontransformlng RNA tumor virus. J. Nat. Cancer Inst.
52(4): 1167-1173. (Cited In U.S. EPA, 1983a)
Schwartz, L. 1898. Concerning the oxidation of acetone and homologous
ketones of the fatty add family. Arch. Exp. Pathol. Pharmakol. 40:
168-194. (Cited 1n U.S. EPA, 1983a)
-18-
-------
Smyth, H.F., Jr., C.P. Carpenter, C.S. Well, U.C. Pozzanl, and J.A.
StMegel. 1962. Range-finding toxldty data: List VI. Am. Ind. Hyg.
Assoc. J. 23: 95-107. (Cited in U.S. EPA, 1983a)
Sollmann, T. 1921. Studies of chronic intoxications on albino rats. II.
Alcohols (ethyl, methyl and "wood") and acetone. J. Pharmacol. Exp. Ther.
16: 291-309. (Cited in U.S. EPA, 1983a)
Tates, A.D. and E. Kriek. 1981. Induction of chromosomal aberrations and
sister-chromatld exchanges in Chinese hamster cells In vitro by some proxi-
mate and ultimate carcinogenic arylamide derivatives. Mutat. Res. 88:
397-410. (Cited in U.S. EPA, 1983a)
Traiger, G.J. and G.L. Plaa. 1973. Effect of amlnotrlazole on isopropanol-
and acetone-induced potentlatlon of CC1 hepatotoxlcity. Can. J. Physlol.
Pharmacol. 51(4): 291-296. (Cited in U.S. EPA, 1983a)
U.S. EPA. 1980. Guidelines and Methodology Used in the Preparation of
Health Effects Assessment Chapters of the Consent Decree Water Quality
Criteria. Federal Register. 45: 79347-79357.
U.S. EPA. 1981. Criteria Document for Acetone. Environmental Criteria and
Assessment Office, Cincinnati, OH. Internal Draft.
U.S. EPA. 1983a. Disposition of Comments on Criteria Document for Acetone.
Environmental Criteria and Assessment Office, Cincinnati, OH. Internal
Draft.
-19-
-------
U.S. EPA. 1983b. Methodology and Guidelines for Reportable Quantity Deter-
minations Based on Chronic Toxldty Data. Prepared by the Environmental
Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid
Waste and Emergency Response, Washington, DC.
Vasavada, H.A. and J.D. Padayatty. 1981. Rapid transfectlon assay for
screening mutagens and carcinogens. Mutat. Res. 91: 9-14. (Cited In U.S.
EPA, 1983a)
Velth, 6.D., D.L. DeFoe and B.V. Bergstedt. 1979. Measuring and estimating
the bloconcentratlon factor of chemicals 1n fish. J. F1sh Res. Board Can.
36: 1040-1048.
Wlgaeus, E., S. Holm and I. Astrand. 1981. Exposure to acetone. Uptake
and elimination 1n man. Scand. J. Work Environ. Health. 7: 84-94. (Cited
1n U.S. EPA, 1983a)
-20-
-------
APPENDIX
Summary Table for Acetone
i
ro
Species Experimental Effect
Dose/Exposure
Inhalation
AIS rat 19,000 ppm transient decrease
In body weight
AIC rat 19,000 ppm transient decrease
In body weight
Maximum
composite
score
Oral
AIS NA NA NA
AIC NA NA NA
Maximum
composite
score
Acceptable Intake
(AIS or AIC)
2096 mg/day
209.6 mg/day
ND
ND
ND
ND
Reference
Bruckner and
Peterson, 1981
Bruckner and
Peterson, 1981
NA
NA
ND = Not derived; NA = not applicable
------- |