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Acetophenone
CASRN 98-86-2
Contents
0321
Acetophenone; CASRN 98-86-2
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 Acetophenone
File On-Line 08/22/1988
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 01/01/1989
Inhalation RfC Assessment (I.B.) no data 08/01/1992
Carcinogenicity Assessment (II.) on-line 02/01/1991
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Acetophenone
CASRN -- 98-86-2
Last Revised -- 01/01/1989
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.
___I.A.1. ORAL RfD SUMMARY
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ---------
General toxicity NOAEL: 10,000 ppm 3000 1 1E-1
(423 mg/kg/day) mg/kg
Rat Oral bw/day
Subchronic Study LOAEL: None
Hagen et al., 1967
*Conversion Factors: Investigators determined that 15.5% volatilized, thus
10,000 ppm x 0.845 = 8450 ppm. Assuming a rat consumes a daily amount of
food equal to 5% of its body weight, 8450 ppm (mg/kg food) x 0.05 kg
food/kg bw = 423 mg/kg/day.
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
Hagan, E.C., W.H. Hansen, O.G. Fitzhugh, et al. 1967. Food flavorings and
compounds of related structure. II. Subacute and chronic toxicity. Food
Cosmet. Toxicol. 5: 141-157.
No effects on growth, hematological values or macroscopic tissue changes were
observed in groups of 10 male and 10 female Osborne-Mendel rats exposed to 0,
1000, 2500 and 10,000 ppm acetophenone in the diet for 17 weeks. Microscopic
examination of the 10,000 ppm group revealed no effects. Thus, the 10,000 ppm
level was the highest concentration at which no effects were observed. Some
loss of the compound from the feed due to volatization was reported;
therefore, the dietary concentration of 10,000 ppm was multiplied by a factor
of 0.845 (based on data provided by the investigators) yielding a NOAEL of
8450 ppm or 423 mg/kg/day assuming that a rat consumes a daily amount of food
equivalent to 5% of its body weight/day as food. Dividing the dose by an
uncertainty factor of 3000 yields the RfD of 0.4 mg/kg/day or 7 mg/day for a
70 kg person.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- 10 for species to species extrapolation, 10 to protect sensitive humans,
10 to extrapolate from subchronic to chronic exposure, and 3 for the lack of
important reproductive toxicity data.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
Single dose oral LD50 values for rats range from 0.9-3.2 g/kg bw indicating
that the subchronic NOAEL defined by Hagan et al. (1967) may be close to the
threshold for toxicity.
Acetophenone has not been tested for carcinogenicity teratogenicity or for
reproductive effects.
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Low
Data Base -- Low
RfD -- Low
The study was given a low confidence level because although the animals were
tested by a relevant route of administration at three levels in a subchronic
study and several endpoints were monitored, the sample size was inadequate and
the range of doses tested did not define a LOAEL. The data base was given a
low confidence level because although NOAELs were defined by Hagan et al.
(1967), supporting studies could not be located in the available literature.
In addition, only one species was tested, and no carcinogenicity,
teratogenicity or reproductive studies could be located in the available
literature. Further, the only supporting data available was acute toxicity
data, which indicated that the NOAEL defined by Hagan et al. (1967) was close
to the threshold of toxicity. Thus, the RfD was given a low confidence level
rating.
___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 -- 10/15/1987
Verification Date -- 10/15/1987
___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 -- Acetophenone
CASRN -- 98-86-2
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Acetophenone
CASRN -- 98-86-2
Last Revised -- 02/01/1991
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 no human data and no animal data.
___II.A.2. HUMAN CARCINOGENICITY DATA
None.
___II.A.3. ANIMAL CARCINOGENICITY DATA
None.
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
In a plate incorporation assay at levels of up to 3000 nmol/plate
acetophenone was not mutagenic when tested for reverse mutations in several
strains of Salmonella typhimurium both in the presence and absence of rat S-9
hepatic homogenates (Elliger et al., 1984). Rahn et al. (1974) found that
acetophenone caused breaks in DNA isolated from E. coli (B(3)T-) after strand
photosensitization.
__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, 1987
The 1987 Health and Environmental Effects Document for Acetophenone has
received peer review and Agency review and is approved for publication.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 11/07/1990
Verification Date -- 11/07/1990
___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 -- Acetophenone
CASRN -- 98-86-2
Last Revised -- 02/01/1991
__VI.A. ORAL RfD REFERENCES
Hagan, E.C., W.H. Hansen, O.G. Fitzhugh, et al. 1967. Food flavorings and
compounds of related structure. II. Subacute and chronic toxicity. Food
Cosmet. Toxicol. 5: 141-157.
__VI.B. INHALATION RfD REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Elliger, C.A., P.R. Henika and J.T. MacGregor. 1984. Mutagenicity of
flavones, chromones and acetophenones in Salmonella typhimurium: New
structure-activity relationships. Mutat. Res. 135: 77-86.
Rahn, R.O., L.C. Landry and W.L. Carrier. 1974. Formation of chain breaks
and thymine dimers in DNA upon photosensitization at 313 nm with acetophenone,
acetone or benzophenone. Photochem. Photobiol. 19(1): 75-78.
U.S. EPA. 1987. Health and Environmental Effects Document for Acetophenone.
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 -- Acetophenone
CASRN -- 98-86-2
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Date Section Description
-------- -------- --------------------------------------------------------
08/22/1988 I.A. Oral RfD summary on-line
01/01/1989 I.A.7. Contacts phone numbers corrected
08/01/1989 VI. Bibliography on-line
12/01/1990 II. Carcinogen assessment now under review
02/01/1991 II. Carcinogenicity assessment on-line
02/01/1991 VI.C. Carcinogen references added
09/01/1991 I.B. Inhalation RfC now under review
01/01/1992 I.A.7. Seondary contact changed
01/01/1992 IV. Regulatory Action section on-line
08/01/1992 I.B. Work group review meeting date added
VIII. SYNONYMS
Substance Name -- Acetophenone
CASRN -- 98-86-2
Last Revised -- 08/22/1988
98-86-2
Acetophenone
acetyl benzene
hypnone
phenyl methyl acetone
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0321.HTM
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