_ TECHNICAL REPORT DATA
(ftette rttd Inttnicnoni on the rtvtnt btfore completing}
1.-REPORT NO.
FPA/60Q/8-89/085
a.
4. TITLE AND SUBTITLE
Updated Health Effects Assessment for Acetone
3 RECIPIENT'S ACCESSION NO
PB90-142373/AS
6. REPORT DATE
«. PERFORMING ORGANIZATION CODE
7. AUTMOR(S)
. PERFORMING ORGANIZATION REPORT NO
PERFORMING ORGANIZATION NAME AND ADDRESS
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
Environmental Criteria and Assessment Office
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati. OH 45268
13. TYPE OF REPORT AND PERIOD COVERED
14. SPONSORING AGENCY CODE
EPA/600/22
5 SUPPLEMENTARY NOTES
6. ABSTRACT
This report summarizes and evaluates information relevant to a preliminary interim
assessment of adverse health effects associated with specific chemicals or compounds.
The Office of Emergency and Remedial Response (Superfund) uses these documents in
preparing cost-benefit analyses under Executive Order 32991 for decision-making under
CERCLA. All estimates of acceptable intakes and carcinogenic potency presented in
this document should be considered as preliminary and reflect limited resources
allocated to this project. The intent in these assessments is to suggest acceptable
exposure levels whenever sufficient data are available. The interim values presented
reflect the relative degree of hazard associated with exposure or risk to the
chemical(s) addressed. Whenever possible, two categories of values have been
estimated for systemic toxicants (toxicants for which cancer is not the endpoint of
concern). The first, RfDs or subchronic reference dose, is an estimate of an exposure
level that would not be expected to cause adverse effects when exposure occurs during
a limited time interval. The RfD 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 lifespan. For compounds for which there is sufficient evidence of
carcinogenicity, qi*s have been computed, if appropriate, based on oral and
inhalation data if available.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS C. COS AT I Field /Group
B. DISTRIBUTION STATEMENT
Public
IB. SECURITY CLASS (THuRtport)
Unclassified
21. NO. OF PAGES
20. SECURITY CLASS (This page/
Unclassified
22. PRICE
EPA f»rm 2220>1 (II**. 4-77) PMKVIOU* COITION it OMOLCTB
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EPA/600/8-89/085
April, 1988
HEALTH EFFECTS ASSESSMENT
FOR ACETONE
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OH 45268
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DISCLAIMER
This document has been reviewed 1n accordance with the U.S. Environ-
mental Protection Agency's peer and administrative review policies and
approved for publication. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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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 In
this document should be considered as preliminary and reflect limited
resources allocated to this project. Pertinent toxlcologlc and environ-
mental data were located through on-Hne literature searches of the TOXLINE,
CANCERLINE and the CHEMFATE/DATALOG data bases. The basic literature
searched supporting this document Is current up to May, 1987. 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. 1987. Integrated Risk Information System (IRIS).
Reference dose {RfD) for oral exposure for acetone. On-Hne.
(Verification date 5/30/86). Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH.
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 In
scope, which tended to generate conservative (I.e., protective) estimates.
Nevertheless, the Interim values presented reflect the relative degree of
hazard associated with exposure or risk to the chemical(s) addressed.
Whenever possible, two categories of values have been estimated for
systemic toxicants (toxicants for which cancer 1s not the endpolnt of
concern). The first, RfD$ (formerly AIS) or subchronlc reference dose, 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 llfespan).
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 In ambient air or water where lifetime
exposure Is assumed. Animal data used for RfD§ 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. These
values are developed for both Inhalation (RfD$i) and oral (RfD$o)
exposures.
The RfD (formerly AIC) 1s similar In concept and addresses chronic
exposure. It 1s 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
RfD Is route-specific and estimates acceptable exposure for either oral
(RfDg) or Inhalation (RfDj) exposure with the Implicit assumption that
exposure by other routes 1s Insignificant.
111
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Composite scores (CSs) for noncardnogens have also been calculated
where data permitted. These values are used for Identifying reportable
quantities and the methodology for their development Is explained In U.S.
EPA (1984).
For compounds for which there 1s sufficient evidence of carclnogenlclty,
RfD$ and RfD values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980). Since cancer Is a
process that Is not characterized by a threshold, any exposure contributes
an Increment of risk. For carcinogens, q-|*s have been computed, If
appropriate, based on oral and Inhalation data 1f available.
1v
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ABSTRACT
In order to place the risk assessment evaluation 1n proper context,
refer to the preface of this docuement. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation of and use of the quantitative estimates presented.
A reevaluatlon of the single Inhalation assessment In the con.text of the
more recent oral evaluation, suggests that the 3 hours/day exposure duration
Is Inadequate for extrapolation to continuous exposure. Therefore neither
an RfDgj nor an RfDj are derived.
The U.S. EPA (1987) has verified an RfDg of 7 mg/day, based on a
90-day oral gavage study In rats. A subchronlc oral RfD$o of 70 mg/day
was also derived from this study. A CS of 6.6 was derived from the 90-day
oral gavage study (U.S. EPA, 1986a).
Data are Inadequate to assess the potential carclnogenlclty of acetone.
The available mutagenlclty data are predominately negative. Acetone Is
placed 1n weight of the evidence Group D, not classifiable as to carclno-
genlclty.
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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 In 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 A1r 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 the following:
Erma Durden and Judith Olsen
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by the
following:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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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
Paqe
1
3
. . . 3
3
4
. . . 4
. . . 4
. , , 5
. . . 5
. . . 5
6
6
. . . 6
6
6
7
. . . 7
. . . 7
7
, , , 7
. . . 7
7
. . . 7
8
. . . 9
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TABLE OF CONTENTS (cont.)
RISK
6.1.
6.2.
6.3.
ASSESSMENT
SUBCHRONIC REFERENCE DOSE (RfDs)
6.1.1. Oral (RfDso)
6.1.2. Inhalation (RfDSI)
REFERENCE DOSE
6.2.1. Oral (RfD0)
6.2.2. Inhalation (RfDj)
CARCINOGENIC POTENCY (qf)
6.3.1. Oral
6.3.2. Inhalation
REFERENCES
Page
10
10
10
10
11
11
12
12
12
12
13
APPENDIX: Summary Table for Acetone .................. 21
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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
Koc Soil sorptlon coefficient standardized
with respect to soil organic matter
Kow Log octanol/water partition coefficient
LD5Q Dose lethal to 50% of recipients
LOAEL Lowest-observed-adverse-effect level
NOAEL No-observed-adverse-effect level
NOEL No-observed-effect level
ppm Parts per million
RBC Red blood cell
RfD Reference dose
RfDj Inhalation reference dose
RfDn, Oral reference dose
RfD$ Subchronlc reference dose
RfDsi Subchronlc Inhalation reference dose
RfD$o Subchronlc oral reference dose
STEL Short-term exposure limit
TLV Threshold limit value
TWA Time-weighted average
1x
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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: 58.08
Chemical class: aliphatic Icetone
Vapor pressure: 185 mm Hg at 20°C Nelson and Webb, 1978
Specific gravity: 0.791 at 20°C Krasavage et al., 1982
Water solubility: mlsdble with water Nelson and Webb, 1978
Log Kow: -0.24 Hansch and Leo, 1985
BCF: 0.12 (estimated)
Koc: 0.015 (estimated) Roy and Griffin, 1985
Half-lives 1n air: 14 hours Graedel, 1978
water: 0.3-1.1 days at 25°C Rathbun et al., 1982
The BCF value of 0.12 was estimated from the equation of Velth et al.
(1979) and the K value given above.
The value for the half-life of acetone 1n the atmosphere 1s based on Its
photolytlc reaction and the rate constant for photolysis given by Graedel
(1978). The half-life of acetone In water 1s based on Its evaporation rate
from water under quiescent to different aerated conditions. The blodegrada-
tlon half-life may be comparable with Us evaporation half-life under
certain conditions (Rathbun et al., 1982); however, blodegradatlon has not
been considered In estimating the aquatic half-life of acetone because of
the lack of available rate constant data.
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
0016H -1- 04/11/88
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acetone 1n wastewater and seawater (Price et al., 1974; Bridle et al., 1979;
Young et al., 1968), It 1s likely that It will undergo significant bio-
degradation 1n soils as well. The undecomposed and unevaporated acetone 1s
expected to leach from soil because of Us high water solubility and weak
sorptlon on soils (Roy and Griffin, 1985). The detection of acetone 1n both
soil leachate and groundwater 1s evidence for Us soil Teachability
(Shackelford and Keith, 1976; NLM, 1987).
0016H -2- 04/11/88
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Without providing documentation, Krasavage et al. (1982) stated that
acetone 1s readily absorbed by all routes of administration. Price and
RHtenberg (1950) noted that gastrointestinal absorption was rapid when a
gavage dose of acetone 1n water was given to rats; acetone 1n expired air
was detected within 20 minutes of dosing and peak levels 1n expired air
occurred between 1 and 2 hours.
2.2. INHALATION
Several studies Indicate that respiratory uptake of acetone Is rapid and
extensive In animals and humans. Kagan (1924) estimated that 71-77% of
Inhaled acetone 1s absorbed by the respiratory tract. Tada et al. (1972)
reported that humans exposed to 600 ppm (1425 mg/m3) absorbed 83% of the
Inhaled dose. No further details of these studies were available. This
summary 1s based upon the review by Krasavage et al. (1972). Wlgaeus et al.
(1981) measured the respiratory rate of humans and the concentration of
acetone 1n Inspired and expired air to determine respiratory retention.
Using exposure concentrations of 300 or 552 ppm (713 or 1311 mg/m3) with
and without exercise, respiratory retention was estimated at 39-52% with a
mean of 45%. Exercise Increased the absolute but not the relative amount of
acetone absorbed when the volume Inspired was compared with the amount
retained. This Is because with exercise ventllatory volume Increases so
when the same relative fraction 1s absorbed there Is an Increase 1n the
total absorbed dose.
0016H -3- 04/11/88
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. LHtle Information regarding the subchronlc toxlclty of
orally administered acetone was located 1n the available literature.
Sollman (1921) exposed three rats to 2.5% acetone 1n drinking water for 18
weeks. Upon termination of the experiment, the animals were found to be
"practically normal," experiencing only weight loss. Although decreased
food consumption was also noted, the authors stated that the growth deficit
could have either been due to decreased food consumption or "the diminished
growth and diminished appetite are both results of a common cause." No
other endpolnts were examined or reported.
Acetone was administered by gavage to groups of 30 male and 30 female
albino rats for 30 or 90 days at levels of 0, 100, 500 or 2500 mg/kg/day
(U.S. EPA, 1986a). No effects were seen at 100 mg/kg/day throughout the
study. Significant Increases 1n the RBC parameters were reported In males
at 30 days and 90 days 1n males (hemoglobin, hematocrlt, corpuscular volume)
and females at 90 days (hemoglobin, hematocrlt) 1n the 2500 mg/kg groups.
Statistically significant Increases 1n kidney weights were reported for
females 1n the 500 and 2500 mg/kg groups and Increased kidney-to-body and
-brain weight ratios were reported for males and females In the 2500 mg/kg
groups. Liver weight and llver-to-body weight ratios were also Increased at
2500 mg/kg 1n males and females. No significant body weight changes were
seen In males. Transient, significantly elevated body weights were seen In
females 1n the two highest dose groups. H1stopatholog1c evaluation revealed
a marked Increase 1n severity of renal tubular degeneration and hyaline
droplet accumulation with Increasing doses, significant at 500 and 2500
mg/kg In males and at 2500 mg/kg 1n females. A NOEL of 100 mg/kg/day and a
LOAEL of 500 mg/kg/day were established from this study (U.S. EPA, 1987).
0016H -4- 04/11/88
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3.1.2. Inhalation. Information regarding the subchronlc toxldty of
Inhaled acetone Is also limited. Bruckner and Peterson (1981a) exposed male
Sprague-Dawley rats to vapors of acetone at levels of either 0 or 19,000 ppm
(45 g/m3), 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 rats exposed to acetone. There were no
treatment-related changes 1n clinical chemistry parameters or hlstologlcal
appearance of the liver, brain, kidneys, lungs or heart 1n this study.
Significant decreases In brain weight were noted after 2 and 4 weeks of
exposure, but not after 8 weeks of exposure or 2 weeks postexposure. Kidney
weights were significantly decreased after 4 weeks of exposure only. The
authors stated that body weights were depressed; the data were not shown.
Bruckner and Peterson (1981b) also reported exposure concentration-related
narcosis 1n male Sprague-Dawley rats exposed to acetone concentrations
>12,600 ppm. Narcosis was measured using wire maneuver, visual placing,
grip strength, tall pinch and righting reflex. Responses were scored on a
scale of 0-8 and the results of the five measures averaged. Responses were
measured at 1, 2 and 3 hours from start of exposure to concentrations of
acetone from 12,600-50,600 ppm. While decrements 1n performance were both
dose-related and exposure time-related, the presentation of data does not
allow for a clear determination of the time point where a decrement first
occurs.
3.2. CHRONIC
3.2.1. Oral. Pertinent data regarding the chronic toxldty of orally
administered acetone were not located 1n the available literature.
0016H -5- 04/12/88
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3.2.2. Inhalation. In occupational exposure studies, workers exposed to
vapors of acetone at >750 ppm (>1782 mg/m3) (Raleigh and McGee, 1972)
complained of Irritation of the mucosal membranes, Including conjunctivitis,
pharyngitis, Inflammatory bronchitis and gastroduodenltls.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenldty 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 teratogenldty of
Inhaled acetone were not located 1n the available literature.
3.4. TOXICANT INTERACTIONS
A number of studies Indicate that acetone potentiates the hepatotoxlc
effects of carbon tetrachloMde (Tralger and Plaa, 1973; Plaa et al., 1982;
Folland et al., 1976), 1,1,2-trlchloroethane, 1,1 ,l-tr1chloroethane (Tralger
and Plaa, 1973; Plaa et al., 1975; MacDonald et al., 1982), dlbromochloro-
methane and trlchloroethane (Hewitt et al., 1983). Acetone was also
reported to antagonize semlcarbazlde-lnduced convulsions In rats (KohH et
al., 1967) and had an additive effect upon the LD5Q 1n rats treated with
acetonltrlle (Smyth et al., 1962).
Glatt et al. (1981) reported that acetone enhanced the mutagenlc
activity of dlmethylnltrosamlne 1n Iji vitro assays but not 1n in vivo assays.
0016H -6- 04/12/88
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4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent data regarding the cardnogenldty of Ingested
acetone were not located 1n the available literature.
4.1.2. Inhalation. Pertinent data regarding the cardnogenldty of
Inhaled acetone were not located 1n the available literature.
4.2. BIOASSAYS
4.2.1. Oral. NTP has scheduled both rat and mouse bloassays Involving
drinking water exposures. Prechronlc testing Is underway. Pertinent data
regarding the cardnogenldty of orally administered acetone were not
located 1n the available literature.
4.2.2. Inhalation. Pertinent data regarding the cardnogenldty of
Inhaled acetone were not located 1n the available literature.
4.3. OTHER RELEVANT DATA
Acetone did not show mutagenlc activity when tested 1n mlcroblal assay
systems (HcCann et al., 1975; Abbondandolo et al.f 1980; Maron et a!., 1981;
Hallstrom et al., 1981) or In cell transformation systems (Freeman et al.,
1973; Rhlm et al., 1974; Quarles et al., 1979a,b). Furthermore, acetone
gave negative results 1n assays that tested for chromosomal aberrations and
sister chromatld exchange (Norppa et al., 1981; Norppa, 1981; Tates and
Krlek, 1981), DNA cell binding (Kublnskl et al., 1981), point mutation In
mouse lymphoma cells (Amacher et al., 1980) and transfectlon (Vasavada and
Padayatty, 1981). In one study, however, acetone was reported to produce
chromosomal aberrations but not sister chromatld exchange (Kawachl et al.,
1980).
0016H -7- 04/11/88
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4.4. WEIGHT OF EVIDENCE
Because data regarding the cardnogenlcHy of acetone 1n humans or In
experimental animals were not located 1n the available literature, the
weight of evidence for the carclnogenldty of acetone In humans Is desig-
nated as Inadequate. Using the scheme for the classification of the
cardnogenlcHy of chemicals to humans adopted by U.S. EPA (1986b), acetone
1s assigned to Weight of the Evidence Group D - not classifiable as to
cardnogenlcHy In humans.
0016H -8- 04/11/88
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5. REGULATORY STANDARDS AND CRITERIA
ACGIH (1986a,b) has recommended a TtV-TWA of 750 ppm (-1780 mg/m3) and
a STEL of 1000 ppm (2375 mg/m3) for occupational exposure to acetone.
These values were chosen to reduce nose and eye Irritation. NJOSH (1978)
has recommended a criterion of 250 ppm (-590 mg/m3) for exposure to
acetone 1n the workplace, while OSHA (1985) has adopted 1000 ppm (2400
mg/m3) as a standard for occupational exposure to acetone.
0016H -9- 07/14/87
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6. RISK ASSESSMENT
6.1. SUBCHRONIC REFERENCE DOSE (RfD$)
6.1.1. Oral (RfDSQ). Data from the Sollman (1921) study cannot be used
to derive an RfDSQ because small numbers of animals were used; there was
only one level of exposure; hlstologlcal endpolnts were not examined; and
control animals were not maintained. As discussed 1n Section 3.1.1. and
according to U.S. EPA (1987), an animal NOEL of 100 mg/kg/day was Identified
from the 90-day gavage study 1n rats (U.S. EPA, 1986a). A LOAEL of 500
mg/kg/day based on Increased liver and kidney weights and nephrotoxIcHy was
also established from the same study. Applying an uncertainty factor of 100
(for Inter- and Intraspecles extrapolation) to the NOEL of 100 mg/kg/day,
results In a RfDso of 1 mg/kg/day, or 70 mg/day for a 70 kg man.
Confidence In the RfDSQ 1s medium by analogy to the confidence statement
appended to the RfD (Section 6.2.1.).
6.1.2. Inhalation (RfDSI). Bruckner and Peterson (1981b) reported that
rats experienced narcosis during 3-hour exposure periods to 12,600 ppm
acetone. In addition, body and organ weights were decreased 1n male rats
during 8 weeks of exposure; however, body and organ weights returned to
control values by 2 weeks after cessation of exposure (Bruckner and
Peterson, 1981b). A NOAEL of 19,000 ppm could be established on the basis
of reversible changes 1n organ and body weights 1n rats.
A previous assessment (U.S. EPA, 1984) utilized this data to develop an
Inhalation AIS. The exposure duration 1n the Bruckner and Peterson (1981a)
study was only 3 hours/day. VUgaeus et al. (1981), 1n a study Involving
acetone exposure to human volunteers, showed that after 2 hours of exposure
blood concentrations of acetone were still rising, showing no signs of a
plateau. In addition, they showed that acetone was cleared very rapidly
0016H -10- 04/11/88
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from the blood following cessation of exposure. These data suggest that a
3-hour exposure time may be Inadequate as a basis for extrapolation to a
continuous exposure scenario. In addition, the previously unavailable oral
data that suggest kidney pathology at lower doses than the projected Inhala-
tion mg/kg/day doses (using an absorption factor of 0.48 based on Wlgaeus et
al., 1981) add an additional note of caution. Therefore, based upon the new
oral data In combination with a revaluation of the applicability of the
experimental exposure regimen, It 1s recommended that the existing animal
data are Inadequate to support calculation of an RfD-j. These data could
be used to suggest benchmark exposure levels for 3 hours/day exposures.
6.2. REFERENCE DOSE (RfD)
6.2.1. Oral (RfDQ). The U.S. EPA (1987) has derived and verified a
chronic RfDQ from the subchronlc gavage study 1n rats discussed 1n Section
3.1.1. (U.S. EPA, 1986a). Following the calculations presented by the U.S.
EPA (1987), an uncertainty factor of 1000 (100 for Inter- and Intraspecles
extrapolation, and 10 to expand from subchronlc to chronic exposure) was
applied to the animal NOEL of 100 mg/kg/day and resulted 1n the verified RfD
of 0.1 mg/kg/day, or 7 mg/day for a 70 kg man. This value, therefore, 1s
adopted as the RfDQ for acetone. U.S. EPA (1987) ranks confidence In the
key study and RfD as medium and confidence 1n the meager data base as low.
A CS for acetone 1s calculated from the oral gavage study In rats
reported by U.S. EPA (1986a). The effects of Increased liver and kidney
weights were observed 1n both male and female rats at a dose of 500 mg/kg/
day. Kidney degeneration was also observed 1n male rats at this dosage.
Therefore, a LOAEL of 500 mg/kg/day was established from this study (U.S.
EPA, 1987). The LOAEL was divided by a factor of 10 to expand from sub-
chronic to chronic exposure and then converted to a human equivalent dosage
0016H -11- 04/11/88
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by multiplication of the animal dose by the cube root of the ratio of the
reference animal body weight of 0.35 kg (U.S. EPA, 1980) to the human
reference body weight of 70 kg (U.S. EPA, 1980) and further by 70 kg,
resulting In a chronic human MED of 598 mg/day. This MED corresponds to an
RV, of 1.3. The effects of Increased liver and kidney weights and kidney
degeneration warrant an RV of 5 and result 1n a CS of 6.5 for acetone.
6.2.2. Inhalation (RfD.). As discussed 1n Section 6.1.2., the only
available animal study (Bruckner and Peterson, 1981) employed a dally
exposure regimen of only 3 hours. Based upon the pharmacoklnetlcs of
acetone 1n terms of pulmonary uptake and considering the newer oral data
(U.S. EPA, 1986a) which suggest kidney pathology at exposure levels that are
lower than those estimated from the Inhalation study, 1t 1s recommended that
an RfD, not be derived.
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
Inhalation exposure to acetone.
0016H -12- 04/11/88
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7. REFERENCES
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0016H -20- 03/02/88
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