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Acetone
CASRN 67-64-1
Contents
0128
Acetone; CASRN 67-64-1
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Acetone
File On-Line 03/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 08/01/1993
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) on-line 12/01/1990
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Acetone
CASRN -- 67-64-1
Last Revised -- 08/01/1993
The oral Reference Dose (RfD) is based on the assumption that thresholds exist
for certain toxic effects such as cellular necrosis. It is expressed in units
of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning
perhaps an order of magnitude) of a daily exposure to the human population
(including sensitive subgroups) that is likely to be without an appreciable
risk of deleterious effects during a lifetime. Please refer to the Background
Document for an elaboration of these concepts. RfDs can also be derived for
the noncarcinogenic health effects of substances that are also carcinogens.
Therefore, it is essential to refer to other sources of information concerning
the carcinogenicity of this substance. If the U.S. EPA has evaluated this
substance for potential human carcinogenicity, a summary of that evaluation
will be contained in Section II of this file.
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.
___I.A.1. ORAL RfD SUMMARY
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ---------
Increased liver and NOEL: 100 mg/kg/day 1000 1 1E-1
kidney weights and mg/kg/day
nephrotoxicity LOAEL: 500 mg/kg/day
Rat Oral Subchronic
Study
U.S. EPA, 1986
*Conversion Factors: Actual dose tested
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
U.S. EPA. 1986. Ninety-day gavage study in albino rats using acetone.
Office of Solid Waste, Washington, DC.
Acetone was administered by gavage for 90 days to groups of albino rats
(30/sex/group) at 0, 100, 500, or 2500 mg/kg/day. Body weights, food
consumption, clinical chemistry, hematology, and histopathologic parameters,
as well as organ weights and organ-to-body weight ratios, were measured and
analyzed. Animals were sacrificed after 30 or 90 days of exposure. No
effects were seen at the 100 mg/kg/day dose level throughout the study. RBC
parameters were significantly increased in the 2500-mg/kg/day group at 30 days
(males only) and at 90 days in males and females. Statistical analysis of the
absolute and relative organ weight data revealed significantly increased
kidney weights for females in the 500- and 2500-mg/kg/day groups and increased
kidney-to-body and brain weight ratios for males and females in the 2500-
mg/kg/day groups. Liver weight and liver/body weight ratios were also
increased in the 2500-mg/kg/day males and females. Histopathologic studies
revealed a marked increase in severity in tubular degeneration of the kidneys
and hyaline droplet accumulation with increasing doses. This accumulation was
significant in the 500- and 2500-mg/kg/day males and the 2500 mg/kg/day
females.
Based on the above findings, the NOEL for this study is 100 mg/kg/day and the
LOAEL is 500 mg/kg/day based on increased liver and kidney weights and
nephrotoxicity.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- An uncertainty factor of 1000 is used; 100 for inter- and intraspecies
extrapolation and 10 to extrapolate from subchronic to chronic exposure.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
Limited human studies have shown that workers exposed to acetone vapors (600
to 2150 ppm) experienced transient eye and nose irritation. Animals exposed
to acetone vapors at 45,134 mg/cu.m experienced slight, but not significant,
decreases in organ and body weights.
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Medium
Data Base -- Low
RfD -- Low
Confidence in the principal study is rated medium, since a moderate number of
animals/dose/sex and an extensive number of parameters were measured. The
data base is rated low because a very limited number of studies are available
and no pertinent supporting studies were located. The overall confidence
rating for the RfD is low.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
Other EPA Documentation -- None
Agency Work Group Review -- 12/18/1985, 05/30/1986, 07/21/1993
Verification Date -- 05/30/1986
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Acetone
CASRN -- 67-64-1
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Acetone
CASRN -- 67-64-1
Last Revised -- 12/01/1990
Section II provides information on three aspects of the carcinogenic
assessment for the substance in question; the weight-of-evidence judgment of
the likelihood that the substance is a human carcinogen, and quantitative
estimates of risk from oral exposure and from inhalation exposure. The
quantitative risk estimates are presented in three ways. The slope factor is
the result of application of a low-dose extrapolation procedure and is
presented as the risk per (mg/kg)/day. The unit risk is the quantitative
estimate in terms of either risk per ug/L drinking water or risk per ug/cu.m
air breathed. The third form in which risk is presented is a drinking water
or air concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1
in 1,000,000. The rationale and methods used to develop the carcinogenicity
information in IRIS are described in The Risk Assessment Guidelines of 1986
(EPA/600/8-87/045) and in the IRIS Background Document. IRIS summaries
developed since the publication of EPA's more recent Proposed Guidelines for
Carcinogen Risk Assessment also utilize those Guidelines where indicated
(Federal Register 61(79):17960-18011, April 23, 1996). Users are referred to
Section I of this IRIS file for information on long-term toxic effects other
than carcinogenicity.
__II.A. EVIDENCE FOR CLASSIFICATION AS TO HUMAN CARCINOGENICITY
___II.A.1. WEIGHT-OF-EVIDENCE CLASSIFICATION
Classification -- D; not classifiable as to human carcinogenicity
Basis -- Based on lack of data concerning carcinogenicity in humans or
animals.
___II.A.2. HUMAN CARCINOGENICITY DATA
None.
___II.A.3. ANIMAL CARCINOGENICITY DATA
None.
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
Acetone did not show mutagenic activity when tested in Salmonella
typhimurium strains TA98 and TA100 or in Schizosaccharomyces pombe strain P1
either in the presence or absence of liver homogenates (McCann et al., 1975;
Abbondandolo et al., 1980; Maron et al., 1981; Hallstrom et al., 1981) or in
cell transformation systems (Freeman et al., 1973; Rhim et al., 1974; Quarles
et al., 1979a,b). Furthermore, acetone gave negative results in assays for
chromosomal aberrations and sister chromatid exchange (Norppa et al., 1981;
Norppa, 1981; Tates and Kriek, 1981), DNA binding (Kubinski et al., 1981),
point mutation in mouse lymphoma cells (Amacher et al., 1980), and
transfection of E. coli CR63 cells (Vasavada and Padayatty, 1981). In one
study, however, acetone was reported to produce chromosomal aberrations but
not sister chromatid exchanges (Kawachi et al., 1980).
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
None.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION EXPOSURE
None.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1988
The 1988 updated Health Effects Document for Acetone has received Agency
review and is approved for publication.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 12/06/1989
Verification Date -- 12/06/1989
___II.D.3. U.S. EPA CONTACTS (CARCINOGENICITY ASSESSMENT)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_VI. BIBLIOGRAPHY
Substance Name -- Acetone
CASRN -- 67-64-1
Last Revised -- 07/01/1990
__VI.A. ORAL RfD REFERENCES
U.S. EPA. 1986. Ninety-day gavage study in albino rats using acetone.
Office of Solid Waste, Washington, DC.
__VI.B. INHALATION RfD REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Abbondandolo, A., S. Bonatti, C. Corsi, et al. 1980. The use of organic
solvents in mutagenicity testing. Mutat. Res. 79: 141-150.
Amacher, D.E., S.C. Paillet, G.N. Turner, V.A. Ray and D.S. Salsburg. 1980.
Point mutations at the thymidine kinase locus in L5178Y mouse lymphoma
cells. 2. Test validation and interpretation. Mutat. Res. 72: 447-474.
Freeman, A.E., E.K. Weisburger, J.H. Weisburger, 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.
Hallstrom, I., A. Sundvall, U. Rannug, R. Grafstrom and C. Ramel. 1981. The
metabolism of drugs and carcinogens in isolated subcellular fractions of
Drosophila melangaster. I. Activation of vinyl chloride, 2-amnioanthrecene
and benzo(a)pyrene as measured by mutagenic effects in Salmonella typhimurium.
Chem. Biol. Inter. 34: 129-143.
Kawachi, T., T. Yahagi, T. Kada et al. 1980. Cooperative programme on
short-term assays for carcinogenicity in Japan. In: Molecular and Cellular
Aspects of Carcinogen Screening Tests. R. Montesano, ed. WHO, IARC, Lyon,
France. p. 323-330.
Kubinski, H., G.E. Gutzke and Z.O. Kubinski. 1981. DNA-cell-binding (DCB)
assay for suspected carcinogens and mutagens. Mutat. Res. 89: 95-136.
Maron, D., J. Katzenellenbogen and B.N. Ames. 1981. Compatability of organic
solvents with the Salmonella/microsome test. Mutat. Res. 88: 343-350.
McCann, J., E. Choi, E. Yamasaki and B.N. Ames. 1975. Detection of
carcinogens as mutagens in the Salmonella/microsome test: Assay of 300
chemicals. Proc. Natl. Acad. Sci. 72(12): 5135-5139.
Norppa, H. 1981. The in vitro induction of sister chromatid exchanges and
chromosome aberrations in human lymphocytes by styrene derivatives.
Carcinogenesis. 2(3): 237-242.
Norppa, H., K. Hemminki, M. Sorsa and H. Vainio. 1981. Effect of
monoSUBSTituted epoxides on chromosome aberrations and SCE in cultured human
lymphocytes. Mutat. Res. 91: 243-250.
Quarles, J.M., M.W. Sega, C.K. Schenley and W. Lijinsky. 1979a.
Transformation of hamster fetal cells by nitrosated pesticides in a
transplacental assay. Cancer Res. 39: 4525-4533.
Quarles, J.M., M.W. Sega, C.K Schenley and R.W. Tennant. 1979b. Rapid
screening for chemical carcinogens: Transforming activity of selected nitroso
compounds detected in a transplacental host-mediated culture system. Natl.
Cancer Inst. Monogr. 51: 257-263.
Rhim, J.S., D.K. Park, E.K. Weisburger and J.H. Weisburger. 1974. Evaluation
of an in vitro assay system for carcinogens based on prior infection of rodent
cells with nontransforming RNA tumor virus. J. Natl. Cancer Inst. 52(4):
1167-1173.
Tates, A.D. and E. Kriek. 1981. Induction of chromosomal aberrations and
sister-chromatid exchanges in Chinese hamster cells in vitro by some proximate
and ultimate carcinogenic arylamide derivatives. Mutat. Res. 88: 397-410.
Vasavada, H.A. and J.D. Padayatty. 1981. Rapid transfection assay for
screening mutagens and carcinogens. Mutat. Res. 91: 9-14.
U.S. EPA. 1988. Updated Health Effects Assessment for Acetone. Prepared by
the Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency
Response, Washington, DC.
_VII. REVISION HISTORY
Substance Name -- Acetone
CASRN -- 67-64-1
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
03/01/1988 I.A.5. Confidence levels revised
07/01/1989 VI. Bibliography on-line
01/01/1990 II. Carcinogen assessment now under review
07/01/1990 II. Carcinogen assessment on-line
07/01/1990 IV.F.1. EPA contact changed
07/01/1990 VI.C. Carcinogen references added
12/01/1990 I.A.2. Text edited
12/01/1990 I.A.7. EPA contacts changed
12/01/1990 II.A.4. Text edited
01/01/1992 IV. Regulatory actions updated
08/01/1993 I.A. Oral RfD noted as pending change
08/01/1993 I.A.6. Work group review date added
VIII. SYNONYMS
Substance Name -- Acetone
CASRN -- 67-64-1
Last Revised -- 03/31/1987
67-64-1
ACETON
Acetone
DIMETHYLFORMALDEHYDE
DIMETHYLKETAL
DIMETHYL KETONE
KETONE, DIMETHYL
KETONE PROPANE
beta-KETOPROPANE
METHYL KETONE
PROPANONE
2-PROPANONE
PYROACETIC ACID
PYROACETIC ETHER
RCRA WASTE NUMBER U002
UN 1090
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0128.HTM
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