EPA-54'1/1-86-003
vvEPA
Environmental Protection
Agency
—~a of Emergency and
Remedial Response
Washington DC 20460
Superfund
Office of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
HEALTH EFFECTS ASSESSMENT
FOR METHYL ETHYL KETONE
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EPA/540/1-86-003
September 1984
HEALTH EFFECTS ASSESSMENT
FOR METHYL ETHYL KETONE
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
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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
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with methyl
ethyl ketone. 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
environmental data were located through on-Hne literature searches of the
Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/OATALOG 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 intent 1n 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 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 chemical(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer is not the endpoint of concern).
The first, the AIS or acceptable Intake subchronlc, Is 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 lifespan). 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 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, is 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 is route specific and estimates acceptable exposure
for a given route with the implicit assumption that exposure by other routes
is Insignificant.
Composite scores (CSs) for noncarcinogens 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 (1983).
For compounds for which there is sufficient evidence of carcinogenlcity,
AIS and AIC 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 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-j*s have been computed based on oral
and inhalation data if available.
111
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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.
A number of subchronlc Inhalation studies 1n experimental animals are
available which suggest threshold exposure levels for liver damage and
neurological Impairment. An AIS for Inhalation of 153.4 mg/day Is estimated
from these studies. No chronic exposure data are available; therefore, an
AIC of 15.3 mg/day has been estimated based on the subchronlc studies. This
estimate should be reviewed when adequate chronic data become available. No
Information concerning consequences of oral exposure to methyl ethyl ketone
could be located. As a result, neither a AIS or AIC for oral exposure are
presented. A CS of 8.8 was calculated for methyl ethyl ketone based on
fetotox1c1ty In rats exposed by Inhalation.
1v
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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 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 Waste
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
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TABLE OF CONTENTS
Page
1. ENVIRONMENTAL CHEMISTRY AND FATE 1
2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS 3
2.1. ORAL 3
2.2. INHALATION 3
3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS 4
3.1. SUBCHRONIC 4
3.1.1. Oral 4
3.1.2. Inhalation 4
3.2. CHRONIC,
3.2.1. Oral 6
3.2.2. Inhalation 6
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS 6
3.3.1. Oral 6
3.3.2. Inhalation 6
3.4. TOXICANT INTERACTIONS 7
4. CARCINOGENICITY 8
4.1. HUMAN DATA 8
4.1.1. Oral 8
4.1.2. Inhalation 8
4.2. BIOASSAYS.
4.2.1. Oral 8
4.2.2. Inhalation 8
4.3. OTHER RELEVANT DATA 8
4.4. WEIGHT OF EVIDENCE 9
5. REGULATORY STANDARDS AND CRITERIA 10
v1
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TABLE OF CONTENTS (cont.)
Page
6. RISK ASSESSMENT 11
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 11
6.1.1. Oral 11
6.1.2. Inhalation 11
6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 13
6.2.1. Oral 13
6.2.2. Inhalation 13
6.3. CARCINOGENIC POTENCY (q-j*) 13
6.3.1. Oral 13
6.3.2. Inhalation 13
7. REFERENCES 14
APPENDIX: Summary Table for Methyl Ethyl Ketone 17
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable intake chronic
AIS Acceptable Intake subchronlc
BCF Bloconcentration factor
CS Composite score
61 Gastrointestinal
LOAEL Lowest-observed-adverse-effect level
MED Minimum effective dose
NOAEL No-observed-adverse-effect level
NOEL No-observed-effect level
ppm Parts per million
RQ Reportable quantity
RV(j Dose-rating value
RVe Effect-rating value
SGPT Serum glutamlc pyruvlc transamlnase
STEL Short-term exposure limit
TLV Threshold limit value
TWA Time-weighted average
V111
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1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties and environmental fate of
methyl ethyl ketone (CAS No. 78-93-3) are summarized below:
Chemical class:
Molecular weight:
Vapor pressure at 20°C:
Water solubility at 20°C:
Log octanol/water
partition coefficient:
B1oconcentrat1on factor:
Half-life 1n air:
Half-life 1n water:
aliphatic ketone
72.1
77.5 mm Hg
268 g/8.
0.26
0.33 (estimated)
14 hours
~ days
Verschueren, 1983
Verschueren, 1983
Lande et al., 1976
Verschueren, 1983
Graedel, 1978
Lande et al., 1976
The BCF for methyl ethyl ketone was estimated from the octanol/water
partition coefficient value given 1n the table and the regression equation
developed by Velth et al. (1979).
The half-life of methyl ethyl ketone 1n aquatic media was not located 1n
the available literature. However, 1n most surface waters, this compound
may blodegrade almost completely within 10 days (Lande et al., 1976). The
evaporative half-life from water was calculated to be ~6 days (Lande et al.,
1976). However, use of the Mackay and Wolkoff (1973) equation for estimating
the evaporative half-life of this compound, which cannot be classified as
"slightly soluble," remains questionable.
Pertinent data regarding the fate and transport of methyl ethyl ketone
In soil could not be located 1n the available literature. Based on Us
relatively high water solubility and low octanol/water partition coeffi-
cient, methyl ethyl ketone 1s expected to have a high soil mobility.
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The two other processes that may account for the significant loss of methyl
ethyl ketone from soil are volatilization and blodegradatlon. By analogy
from aquatic media, the half-life of methyl ethyl ketone 1n soils can be
speculated to be about a few days.
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Quantitative data on the oral absorption of methyl ethyl ketone are not
available, but absorption from the 61 tract can be Inferred from systemic
toxic effects observed after acute oral administration (Lande et al., 1976).
2.2. INHALATION
Quantitative data on the pulmonary absorption of methyl ethyl ketone are
not available, but absorption from the lungs can be Inferred from systemic
toxic effects observed after acute and subchronlc Inhalation exposures
(Lande et al., 1976).
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Pertinent data regarding the effects on humans or experi-
mental animals of oral exposure to methyl ethyl ketone could not be located
1n the available literature.
3.1.2. Inhalation. The subchronlc Inhalation studies on methyl ethyl
ketone are summarized 1n Table 3-1. Cavender et al. (1983) exposed both
sexes of rats to methyl ethyl ketone at concentrations of 0, 1250, 2500 or
5000 ppm, 6 hours/day, 5 days/week, for 90 days. There were no treatment-
related effects at the 1250 ppm level; SGPT activity In female rats was
elevated at the 2500 ppm level. At the 5000 ppm level, effects were more
severe and Included depressed mean body weight; slight but significant
Increases In liver weight, I1ver-to-body weight ratio, and I1ver-to-bra1n
weight ratio; significantly decreased SGPT activity; and Increased alkaline
phosphatase, potassium and glucose values 1n treated females. A NOAEL for
Increased SGPT activity of 2500 ppm of methyl ethyl ketone can be suggested
for rats from this study.
Exposure of rats to methyl ethyl ketone at a level of 200 ppm, 12 hours/
day, 7 days/week for 24 weeks resulted 1n slight neurological effects
visible only at 4 months of treatment (Takeuchl et al., 1983), but exposure
of rats to 1125 ppm continuously for 5 months did not result In neuropathy,
defined 1n terms of paralysis (Salda et al., 1976). In both studies, only a
single toxlcologlcal endpolnt, either motor nerve conduction velocity, mixed
nerve conduction velocities, or distal motor latency (Takeuchl et al., 1983)
or paralysis (Salda et al., 1976), was examined.
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TABLE 3-1
Subchronlc Inhalation Toxlclty Testing of Methyl Ethyl Ketone*
Species/Strain Sex Number
at Start
Exposure
Effects
Reference
Rats/F344
H/F
Rats/W1star
i
Rats/NR
Rats/NR
Rats/Sherman
Guinea ptgs/NR
Guinea pigs/
mixed strains
NR
NR
H/F
NR
15/sex/
exposure
level
8/exposure
level
NR
25
15/sex/
exposure
level
15
10/dose
level
0. 1250. 2500 or 5000 ppm.
6 hours/day, 5 days/week.
for 90 days
0 or 200 ppm. 12 hours/day.
7 days/week, for 24 weeks
0 or 1125 ppm continuously
for 5 months
0 or 235 ppm, 7 hours/day,
5 days/week, for 7 weeks
0. 125. 250. 500 or 1000
ppm, for 30 days (hours/day
and days/week, NR)
0 or 235 ppm, 7 hours/day,
5 days/week, for 7 weeks
0. 125, 250, 500 or 1000
ppm, for 30 days (hours/day
and days/week. NR)
No neuropathologlc or hlstopathologlc changes
and no effect on clinical parameters or growth
at the 1250 ppm level. At the 2500 ppm level.
female rats had elevated SGPT activity. At the
5000 ppm level, treatment-related effects In-
cluded depressed mean body weight; slight but
significant Increases In liver weight, liver to
body weight ratio, and liver to brain weight
ratio; significantly decreased SGPT activity;
and Increased alkaline phosphatase, K. and
glucose values In treated females.
No effect on body weight; significantly
Increased motor nerve conduction velocity and
mixed nerve conduction velocities after 4 weeks
of exposure, but not after 24 weeks; signif-
icantly decreased distal motor latency after
4 weeks of exposure, but not after 24 weeks.
No neuropathy, defined tn terms of paralysis,
was observed. No other toxlcologlcal endpolnts
were evaluated.
No significant difference from controls In
growth, hematologtcal or pathological examina-
tion.
No significant hlstopathologlcal changes In
lung, liver or kidney.
No significant difference from controls In
growth, hematologlcal or pathological examina-
tion.
No statistically significant deviation from
controls In body, liver or kidney weights.
Cavender et al.. 1983
TakeucM et al.. 1983
Salda et al.. 1976
LaBelle and Brleger,
1955
Mellon Institute, 1950
LaBelle and Brleger,
1955
Mellon Institute, 1950
*PurHy of compound was not reported
NR = Not reported
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LaBelle and BMeger (1955) observed no effects of exposure to 235 ppm of
methyl ethyl ketone, 7 hours/day, 5 days/week, for 7 weeks, on growth,
hematological or pathological parameters of rats and guinea pigs. Likewise,
exposure to 0, 125, 250, 500 or 1000 ppm for 30 days had no effect on rats
and guinea pigs (Mellon Institute, 1950).
3.2. CHRONIC
3.2.1. Oral. Pertinent data regarding the chronic oral toxicity of
methyl ethyl ketone to humans or experimental animals could not be located
in the available literature.
3.2.2. Inhalation. Pertinent data regarding the chronic inhalation
toxidty of methyl ethyl ketone to humans or experimental animals could not
be located in the available literature.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenicity of methyl ethyl
ketone following oral administration could not be located in the available
literature.
3.3.2. Inhalation. Schwetz et al. (1974) exposed pregnant Sprague-Dawley
rats to methyl ethyl ketone by inhalation at levels of 1000 or 3000 ppm for
7 hours/day on days 6-15 of gestation. There was no maternal toxidty at
either exposure level. Somewhat decreased fetal body measurements (body
weight and cr,own-to-rump length) were seen at the lower but not at the
higher exposure level. At the 1000 ppm level, a significant increase in
litters having fetuses with skeletal abnormalities was seen; however, there
was no significant increase in specific gross, soft-tissue or skeletal
anomalies. At the 3000 ppm level, a significant Increase in litters having
fetuses with gross external anomalies or internal soft-tissue anomalies was
seen.
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3.4. TOXICANT INTERACTIONS
Combined exposure to 100 ppm of n-hexane and 200 ppm of methyl ethyl
ketone for 24 weeks resulted In neurotoxic effects (defined as changes 1n
motor nerve conduction velocity, distal motor latency and mixed nerve con-
duction velocities) 1n rats that were not observed when either chemical was
tested by Itself (Takeuchl et a!., 1983). Hewitt et al. (1983) found that
methyl ethyl ketone potentiated the hepatotoxlc response of chloroform 1n
rats. There was a positive significant correlation between the carbon chain
length of ketones and the severity of the potentiated chloroform-Induced
liver damage.
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4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent data regarding the carcinogenic effects on humans
as a result of oral exposure to methyl ethyl ketone could not be located 1n
the available literature.
4.1.2. Inhalation. Pertinent data regarding the carcinogenic effects on
humans as a result of Inhalation exposure to methyl ethyl ketone could not
be located 1n the available literature.
4.2. BIOASSAYS
4.2.1. Oral. Pertinent data regarding the carcinogenic effects on
experimental animals as a result of oral exposure to methyl ethyl ketone
could not be located 1n the available literature. Methyl ethyl ketone Is
not scheduled for carclnogenlcHy testing by the National Toxicology Program
(NTP, 1983).
4.2.2. Inhalation. Pertinent data regarding the carcinogenic effects on
experimental animals as a result of Inhalation exposure to methyl ethyl
ketone could not be located 1n the available literature. Methyl ethyl
ketone 1s not scheduled for carclnogenlcHy testing by the National Toxicol-
ogy Program (NTP, 1983).
4.3. OTHER RELEVANT DATA
Schwetz et al. (1974) concluded that In rats methyl ethyl ketone Is
embryotoxlc, fetotoxlc and potentially teratogenlc at exposure levels of
1000 or 3000 ppm by Inhalation for 7 hours/day on days 6-15 of gestation.
There were no apparent effects on dams at either exposure level.
Pertinent data regarding the mutagenldty of methyl ethyl ketone could
not be located In the available literature.
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4.4. WEIGHT OF EVIDENCE
Methyl ethyl ketone has not been tested for cardnogenldty by the oral
or Inhalation routes. No tumors were observed during pathological examina-
tions 1n subchronlc tox1c1ty tests (see Section 3.1.2.). IARC has not eval-
uated the risk to humans associated with oral or Inhalation exposure to
methyl ethyl ketone. Applying the criteria proposed by the Carcinogen
Assessment Group of the U.S. EPA for evaluating weight of evidence (Federal
Register, 1984), no data were available regarding the cardnogenldty of
methyl ethyl ketone 1n humans or animals, and the chemical 1s most appro-
priately designated a Group D - Not Classified chemical.
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5. REGULATORY STANDARDS AND CRITERIA
ACGIH (1983) set a TLV-TWA of 200 ppm (590 mg/m3) and a STEL of 300
ppm (885 mg/m3) for methyl ethyl ketone. The basis for these standards is
the minimization of eye and nose irritation rather than the prevention of
systemic toxic effects (ACGIH, 1980).
The OSHA standard for methyl ethyl ketone is 200 ppm (590 mg/m3) as an
8-hour TWA for a 40-hour work week (Code of Federal Regulations, 1981).
ACGIH (1980) summarized the standards in other countries as follows: 200
ppm in West Germany (1974); 150 ppm in Sweden (1974); 100 ppm in East
Germany (1973); and 100 ppm in USSR (1966), Yugoslavia (1971) and Hungary
(1974).
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral. The lack of subchronlc oral toxldty data precludes the
derivation of an AIS for subchronlc exposure to methyl ethyl ketone.
6.1.2. Inhalation. Several subchronlc Inhalation studies have been done
on methyl ethyl ketone. Two of these studies are not useful for risk
assessment, the study by Salda et al. (1976) 1n which only one toxlcologlcal
endpolnt was evaluated and the study by Mellon Institute (1950) In which
complete exposure data were not evaluated and a short duration of exposure
(30 days) was used.
A NOEL of 235 ppm for methyl ethyl ketone In rats and guinea pigs can be
suggested from the study of LaBelle and Brleger (1955). For Identifying the
toxic threshold for methyl ethyl ketone, the studies by Cavender et al.
(1983) and Takeuchl et al. (1983) are most useful, as both studies define a
NOAEL. NOAELs of 2500 ppm of methyl ethyl ketone for Increased S6PT activ-
ity 1n female rats {Cavender et al., 1983) and 200 ppm for temporary slight
neurological effects 1n rats (Takeuchl et al., 1983) can be suggested from
these studies. A LOAEL of 1000 ppm for skeletal abnormalities 1n rat
fetuses (Schwetz et al., 1974) must also be considered.
The corresponding doses for rats 1n units of mg/kg/day for the NOEL of
235 ppm (LaBelle and Brleger, 1955), the NOAELs of 200 ppm (Takeuchl et al.,
1983) and 2500 ppm (Cavender et al., 1983), and the LOAEL of 1000 ppm
(Schwetz et al., 1974) are 107.3, 219.1, 978.1 and 639.0 mg/kg/day, respec-
tively. The equation and calculations are as follows:
dA (mg/kg/day) = C (mg/m3) x E (hours/24 hours) x
D (days/7 days) x IR (mVday) * WA (kg)
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where
d/y = exposure dose for the experimental animal 1n units of
mg/kg/day;
C = concentration of toxicant 1n units of mg/m3;
E = number of hours/day that the animals were exposed divided by
24 hours;
0 = number of days/week that the animals were exposed;
WA = body weight of the experimental animal 1n kg; and
IR = Inhalation rate of the experimental animal in units of mVday.
For the NOEL of 235 ppm:
693.1 mg/m3 x 7 hours/24 hours x 5 days/7 days x 0.26 mVday -r 0.35 kg =
107.3 mg/kg/day
For the NOAEL of 200 ppm:
589.9 mg/m3 x 12 hours/24 hours x 7 days/7 days x 0.26 mVday -=• 0.35 kg =
219.1 mg/kg/day
For the NOAEL of 2500 ppm:
7373.8 mg/m3 x 6 hours/24 hours x 5 days/7 days x 0.26 mVday * 0.35 kg =
978.2 mg/kg/day
For the LOAEL of 1000 ppm:
2949.5 mg/m3 x 7 hours/24 hours x 7 days/7 days x 0.26 mVday * 0.35 kg =
639.1 mg/kg/day
The NOAEL of 200 ppm (219.1 mg/kg/day) is chosen to derive an inhalation
AIS, as it is the largest NOEL or NOAEL dose that 1s less than the LOAEL of
1000 ppm (639.0 mg/kg/day) for skeletal abnormalities 1n rat fetuses. An
uncertainty factor of 100 is applied to the animal dose of 219.1 mg/kg/day
to convert animal to human data and to protect the more sensitive Individ-
uals of a population. This results in an AIS of 2.191 mg/kg/day or 153.4
mg/day for a 70 kg human.
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6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral. The lack of chronic oral toxlclty data precludes the
derivation of an AIC for chronic exposure to methyl ethyl ketone.
6.2.2. Inhalation. There are no chronic studies available from which to
derive a chronic Inhalation Interim ADI for methyl ethyl ketone. The
TLV-TWA of 200 ppm (ACGIH, 1983) cannot be used to derive an AIC, as this
criterion 1s based on eye and nose Irritation rather than on systemic toxic
effects. The subchronlc Inhalation study by Takeuchi et al. (1983), how-
ever, can be used to derive this value. An additional safety factor of 10
must be applied to the AIS of 2.191 mg/kg/day or 153.4 mg/day for a 70 kg
human to convert from subchronlc to chronic data. This results 1n an
Inhalation AIC of 0.2191 mg/kg/day or 15.34 mg/day for a 70 kg human.
An RQ was calculated based on fetotoxlclty (Schwetz et al., 1974)
observed In rats exposed to methyl ethyl ketone at 1000 ppm (2949 mg/m3)
for 7 hours/day- on days 6-15 of gestation. A human MED was calculated by
expanding to continuous exposure, assuming a human breathing rate of 20
mVday and an absorption efficiency of 0.5, and applying an uncertainty
factor of 10 to extrapolate from subchronlc to chronic exposure. A human
MED of 860.1 mg/day was calculated, corresponding to an RV, of 1.1. The
fetotoxlclty observed at this exposure corresponds to an RV of 8. A CS
of 8.8 1s calculated as the product of RV. and RV .
d e
6.3. CARCINOGENIC POTENCY (q *)
6.3.1. Oral. The lack of oral cardnogenlcity data precludes the deriva-
tion of a carcinogenic potency for oral exposure to methyl ethyl ketone.
6.3.2. Inhalation. The lack of Inhalation cardnogenlcity data precludes
the derivation of a carcinogenic potency for Inhalation exposure to methyl
ethyl ketone.
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7. REFERENCES
AC6IH (American Conference of Governmental Industrial Hygienists). 1980.
Methyl Ethyl Ketone. Documentation of the Threshold Limit Values, 4th ed.
with supplements through 1983. p. 279.
ACGIH (American Conference of Governmental Industrial Hygienists). 1983.
Threshold Limit Values for Chemical Substances and Physical Agents in the
Workroom Environment with Intended Changes for 1984. Cincinnati, OH.
Cavender, F.L., H.W. Casey, H. Salem, J.A. Swenberg and E.J. Garalla. 1983.
A 90-day vapor inhalation toxicity study of methyl ethyl ketone. Fund.
Appl. Toxicol. 3(4): 264-270.
Code of Federal Regulations. 1981. OSHA Safety and Health Standards.
Subpart Z - Toxic and Hazardous Substances. 29 CFR 1910.1000.
Federal Register. 1984. Environmental Protection Agency. Proposed Guide-
lines for Carcinogenic Risk Assessment. 49 FR 46294-46299.
Graedel, T.E. 1978. Chemical Compounds in the Atmosphere. Academic Press,
NY. p. 187.
Hewitt, W.R., E.M. Brown and G.L. Plaa. 1983. Relationship between the
carbon skeleton length of ketonic solvents and potentiation of chloro-
form-induced hepatotoxicity in rats. Toxicol. Lett. 16(3-4): 297-304. (CA
98:22111146)
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LaBelle, C.W. and H. Brleger. 1955. Vapour toxldty of a composite solvent
and Us principal components. Arch. Ind. Health. 12: 623-627. (Cited 1n
Lande et al., 1976)
Lande, S.S., P.R. Durkln, O.H. Christopher, P.M. Howard and J. Saxena.
1976. Investigation of Selected Potential Environmental Contaminants:
Ketonlc Solvents. Prepared under Contract No. 68-01-3100. U.S. EPA, Office
of Toxic Substances, Washington, DC. EPA 560/2-76-003.
Mackay, D. and A.W. Wolkoff. 1973. Rate of evaporation of low solubility
contaminants from water bodies to atmosphere. Environ. Sc1. Techno!. 7:
611-614.
Mellon Institute. 1950. Methyl Ethyl Ketone, Report 14-33, unpublished,
Union Carbide Corporation. (Cited 1n Lande et al., 1976)
NTP (National Toxicology Program). 1983. Chemicals on Standard Protocol.
Management Status Report dated 12/5/83.
Salda, K., J.R. Mendell and H.S. Weiss. 1976. Peripheral nerve changes
Induced by methyl n-butyl ketone and potentlatlon by methyl ethyl ketone.
J. Neuropathol. Exp. Neurol. 35: 207-225.
Schwetz, B.A., B.K.J. Leong and P.J. GehMng. 1974. Embryo- and fetotox-
Iclty of Inhaled carbon tetrachloMde, 1 ,l-d1chloroethane and methyl ethyl
ketone In rats. Toxlcol. Appl. Pharmacol. 28(3): 452-464.
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Takeuchl, Y., Y. Ono, N. Hlsanaga, et al. 1983. An experimental study of
the combined effects of n-hexane and methyl ethyl ketone. Br. J. Ind. Med.
40(2): 199-203.
U.S. EPA. 1980. Guidelines and Methodology Used 1n the Preparation of
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-16-
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APPENDIX
Summary Table for Methyl Ethyl Ketone
Species
Inhalation
AIS rats
AIC rats
_;_, Maximum rats
-j composite
score
Oral
AIS NA
AIC NA
Experimental
Dose/Exposure
200 ppm
200 ppm
1000 ppm
(2949 mg/m3),
7 hours/day on days
6-15 of gestation
(RVd=l.l)
NA
NA
Effect Acceptable Intake
(AIS or AIC)
temporary slight 153.4 nig/day
neurological effects
temporary slight 15.34 mg/day
neurological effects
fetotoxlclty 8.8
(Rve=8)
NA ND
NA ND
Reference
Takeuchl
et al.,
Takeuchl
et al.,
Schwetz
et al..
NA
NA
1983
1983
1974
NA = Not applicable; ND = not derived
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