Methyl ethyl ketone
Toxic Tips
INTRODUCTION
Chemical and Physical Description
Methyl ethyl ketone, C4H8O, also known as
2-butanone, methyl acetone, ethyl methyl
ketone, and MEK, is a ketone that has both a
methyl group and an adjacent ethyl group.1 It is
a colorless liquid with a minty or acetone-like
odor.2 MEK is soluble in water and miscible in
alcohol, ether, and benzene.3 It is highly vola-
tile and flammable.4 MEK vapor is heavier than
air, having a density of 0.805 g/cm3 at 20 8C.1,4
The CAS registry number for methyl ethyl ke-
tone is 78-93-3. Its molecular weight is 72.11.5
Uses and Typical Exposure Situations
Methyl ethyl ketone is used as a solvent in the
manufacture and application of paints and
paint removers, acrylic coatings, varnishes,
and adhesives. It is used in food and pharma-
ceutical production and processing. MEK is
also used as a sterilizing agent for bacterial
spores on surgical instruments, dental instru-
ments, and hypodermic needles. According to
the National Occupational Exposure Survey
(NOES) conducted by the National Institute
for Occupational Safety and Health (NIOSH)
from 1981 to 1983, an estimated 1,400,000
workers are potentially exposed to MEK in
the U.S. MEK can enter the water supply via
cement at the joint connections of PVC pipe.
MEK can also be found in tobacco smoke.6,7
MEK is a natural component of various
foods including milk, cheese, raw chicken
breast, and nectarines. It is released into the
atmosphere by plants and animals as a meta-
bolic byproduct. It is also emitted by volcanoes
and forest fires.6,7
Metabolism and Pharmacokinetics
Methyl ethyl ketone is absorbed rapidly by
respiratory and dermal routes.8 Due to its sol-
ubility in water, MEK is more rapidly absorbed
by moist skin than dry skin.6,7 When applied to
dry skin, a plateau for the concentration of
MEK in exhaled air is reached in 4–5 hours.
But when MEK is applied to moist skin, it can
be detected in expired air within 30 seconds
and reaches maximum concentration around
10-15 minutes after application.6 Because
MEK is water soluble, it is easily distributed
in the blood throughout the body. Because it
is lipid soluble, MEK is evenly distributed
among the tissues.9 MEK is metabolized to
1871-5532 ß Division of Chemical Health and Safety of the American Chemical Society
http://dx.doi.org/10.1016/j.jchas.2015.06.007
3-hydroxy-2-butanone, which is then reduced
to 2,3-butanediol and a small portion is revers-
ibly converted to 2-butanol.6 2,3-butanediol is
eventually metabolized to carbon dioxide and
water.9 The majority of MEK is eliminated as
carbon dioxide and water, primarily through
the lungs.7 MEK is quickly removed from the
blood, having a plasma half-life ranging from
46 to 96 minutes in humans.7 2-3% of MEK
absorbed into the body is eliminated un-
changed via exhalation.9 Another 3% on aver-
age is eliminated in the urine as metabolites
2,3-butanediol and 3-hydroxy-2-butanone.8,9
There is insufficient evidence to support that
MEK accumulates in body tissues.4
PATHOPHYSIOLOGY
Determinants of Toxicity
The airborne concentration of methyl ethyl
ketone, the respiratory rate of the individual,
and the time of exposure to the contaminated
air determine the amount of toxicant absorbed
through the respiratory system. The area of skin
exposed, the concentration of the MEK, the
moisture of the skin, and the length of time of
skin contact determine the amount of MEK
absorbed through the skin.6
Mechanisms of Action
MEK is known to potentiate the neurotoxicity of
unbranched aliphatic hexacarbons, such as n-
hexane. MEK also potentiates hepatic and renal
toxicity of haloalkanes.7 In one study, the effects
of n-hexane, MEK, and a combination of both
solvents were studied in rats. The solvents
caused axon swelling by dramatically multiply-
ing the number of neurofilaments. Other non-
specific alterations also occurred, including
accumulation of clusters of phospholipids in
the cytoplasm of Schwann cells and the accu-
mulation of both phospholipids and glycogen in
the axoplasm of nerve fibers. Schwann cells also
underwent degenerative changes.7 Additionally,
MEK induces microsomal P450 activity. So re-
peated exposures may enhance the metabolism
of future exposures to MEK.6
CLINICAL PRESENTATION
Effects Following Inhalation
MEK is known to cause irritation to the respi-
ratory tract. Breathing MEK vapors can cause
33
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sufficient irritation of the mucous
membranes of the nose and throat
leading to coughing and wheezing.
When sufficient concentrations are
inhaled, dizziness, lightheadedness,
headache, nausea, vomiting, and un-
consciousness can occur.1,10 Expo-
sures to high levels of MEK can
potentially cause damage to both the
peripheral nervous system (PNS) and
central nervous system (CNS).11
Effects Following Skin Exposure
MEK is a known skin irritant. Expo-
sure can cause a rash or burning feel-
ing.10 Repeated exposure can cause
inflammation and defatting of the
skin.4
Effects Following Eye Exposure
Direct contact of the eyes with MEK
can cause irritation, burning, and cor-
nea damage.4
Carcinogenicity
Since there are no human carcinoge-
nicity data and inadequate animal da-
ta, the carcinogenicity of MEK cannot
be determined at this time.7 However,
mechanism-based structure-activity re-
lationship (SAR) analysis determined
that MEK is not likely to be carcinogen-
ic. This type of analysis involves com-
paring a compound with unknown
carcinogenic activity to compounds
with a similar structure and known
carcinogenic activity. Specifically, the
structural features, functional proper-
ties, and probable mechanism(s) of
action are evaluated.12
Reproductive Effects
Although it has been reported that
MEK can cross the placenta and enter
the human fetus, there is insufficient
data to determine if MEK is a teratogen
in humans.7 One study in mice showed
a statistically significant increase in the
incidence of misaligned sternebrae in
fetuses whose mothers were exposed
to MEK for ten days at a concentration
of 3,000 ppm during gestation (ster-
nebrae are segments of bone in fetuses
that fuse later in development to form
the sternum).13 The authors of this
study concluded that MEK vapors at
such levels cause mild developmental
toxicity. MEK should be treated as a
34
possible teratogen until more data is
available.10
FIRST AID AND CLINICAL
MANAGEMENT
In the case of high exposure by inhala-
tion, move the individual to fresh air.
Monitor the individual for breathing
difficulties and administer oxygen if
necessary. Mouth to mouth resuscita-
tion should only be used if absolutely
necessary. If MEK is ingested, the
mouth of the individual should be
rinsed with water and the contents spit
out. Vomiting should not be induced. If
eye exposure occurs, the eyes of the
individual should be rinsed thoroughly
with water for ten minutes. If skin ex-
posure occurs, any contaminated cloth-
ing should be removed and the exposed
skin should be thoroughly cleaned with
soap and water. In severe exposure
cases, further medical treatment should
be provided as quickly as possible.4
HANDLING AND EXPOSURE
Accidental Release Measures
If a spill occurs, all sources of ignition
should be immediately shut off and the
area evacuated.4 The spilled liquid
should be absorbed with an inert absor-
bent such as diatomite, vermiculite, or
sand. Dispose of the absorbent using
methods approved by your Environ-
mental Protection office.1,4 Respiratory,
eye and hand protection should be worn
during clean up. The area where the spill
occurred should be well ventilated and
decontaminated .4 MEK fires should be
extinguished with alcohol foam, carbon
dioxide, or dry chemicals.11
Storage Guidelines
MEK should be stored in tightly closed
containers in cool, well-ventilated areas.
It should be stored away from sources of
ignition and heat.4,10 MEK should be
kept away from strong oxidizers.1 Con-
tainers of MEK should be clearly and
permanently labeled. Use original con-
tainers as much as possible.4
Reactivities and Incompatibilities
MEK is incompatible with strong
oxidizers, such as trichloromethane/
Journal of Chemical Health & Safety, July/August 2015
alkali chromium trioxide. It will ignite
on contact with potassium tert-butox-
ide. MEK can form an explosive mix-
ture with air.4,11
MEK produces explosive peroxides
when reacted with hydrogen peroxide
and hydrogen ion. Hydrogen ions (H+)
can originate from acid solutions, such
as nitric acid or sulfuric acid.4 Seven of
these peroxides have been identified:
1,4,7-Trimethyl-1,4,7-triethyl-1,4,7-
cyclononatriperoxane (I); 1,4,7,10,13,
16-Hexamethy1-1,4,7,10,13,16-hex-
aethyl-1,4,7,10,13-pentaperoxy-l,16-
dihydroperoxide (II); 1,4,7,10,13-Pen-
tamethyl-l,4,7,10,13-pentaethyl-l,4,7,
10-tetraperoxy-1,13-dihydroperoxide
(III); 1,4,7,10-Tetramethy1-1,4,7,l0-tet-
raethyl-l,4,7-triperoxy-1,l0-dihydroper-
oxide; 2,20 -dihydroperoxy-2,20 -dibutyl
peroxide (VI); 2,2-dihydroperoxybu-
tane;1,4,7-Trimethyl-l,4,7-triethyl-l,4-
diperoxy-l,7-dihydroperoxide (V); and
2,2-Dihydroperoxybutane (VII). The
most abundant product is 2,20 -dihydro-
peroxy-2,20 -dibutyl peroxide (VI). The
reaction mechanism of this product is
shown in Figure 1, which is entitled
Synthesis of a Peroxide From Methyl
Ethyl Ketone and Hydrogen Peroxide.
In reaction 1 of the mechanism, MEK,
hydrogen peroxide, and H+ react re-
versibly and form 2-hydroperoxy-2-bu-
tanol. This intermediate reacts with
hydrogen peroxide and H+ in reaction
2, forming 2,2-dihydroperoxybutane
and water. The 2,2-dihydroperoxybu-
tane then reacts with 2-hydroperoxy-
2-butanol and H+ in reaction 3, produc-
ing 2,2 0 -dihydroperoxy-2,2 0 -dibutyl
peroxide and water. The other, less
abundant products are formed by 2,20 -
dihydroperoxy-2,20 -dibutyl peroxide
continuing to react with the intermedi-
ate 2-hydroperoxy-2-butanol.14,15
Mixing MEK with 2-propanol will
also produce explosive peroxides.
MEK reacts vigorously with chloroform
and alkali. Other incompatibilities of
MEK include oleum, chlorosulfonic ac-
id, isocyanates, pyridines, amines, am-
monia, and inorganic acids.4,11
EXPOSURE CONTROLS
Sampling and Analysis
The Occupational Safety and Health
Administration (OSHA) calls for the
[(Figure_1)TD$IG]
Figure 1. Synthesis of a peroxide from methyl ethyl ketone and hydrogen peroxide.
use of SKC Anasorb CMS (carbon
molecular sieves) sampling tubes with
calibrated personal air sampling
pumps. Diffusive samples can be col-
lected by exposing SKC 575-002 pas-
sive samplers or 3 M 3520 organic
vapor monitors (OVMs) to workplace
air. The MEK is desorbed with carbon
disulfide containing 1% N,N-dimethyl-
formamide. Analysis is performed by
gas chromatography (GC) with a flame
ionization detector.16
Exposure Guidelines
The American Conference of Govern-
mental Industrial Hygienists (ACGIH)
threshold limit value-time weighted
average (TLV-TWA) for methyl ethyl
ketone is 200 ppm averaged over an 8-
hour workshift. The short term expo-
sure limit (STEL) is 300 ppm. The bio-
logical exposure index (BEI) for MEK
is 2 mg MEK/L urine collected at the
Journal of Chemical Health & Safety, July/August 2015
end of a work shift.17 The NIOSH
recommended exposure limit (REL)
is 200 ppm averaged over a 10-hour
workshift and 300 ppm, not to be
exceeded during any 15 minute peri-
od.10 The OSHA permissible exposure
limit (PEL) is 200 ppm averaged over
an 8-hour workshift.11 The odor
threshold range for MEK is 0.07-
339 ppm. Most sources reported the
odor threshold to be well below the
TLV-TWA and PEL values. Only one
source reported an odor threshold
range (34-339 ppm) that reached
above the TLV-TWA and PEL
values.18
PERSONAL PROTECTION
When working in an area where there
is potential for exposure to MEK,
solvent-resistant gloves and clothing
should be worn. Butyl rubber is recom-
mended for use as a protective materi-
al. Indirect-vent, impact and splash
resistant goggles should also be worn.
When there is potential for exposure
over the TLV-TWA value, a MSHA/
NIOSH approved full facepiece respi-
rator with an organic vapor cartridge
should be worn. When there is poten-
tial for higher exposure, a NIOSH ap-
proved supplied-air respirator with a
full facepiece should be worn and op-
erated in a pressure-demand or other
positive-pressure mode.10
REFERENCES
1. National Institute for Occupational
Safety and Health (NIOSH).
[8_TD$IF]International Chemical Safety Cards
(ICSC): Methyl Ethyl Ketone[8_TD$IF]. Accessed
from http://www.cdc.gov/niosh/ipcsneng/
neng0179.html[9_TD$IF] on January 21, 2015.
35
2. National Institute for Occupational cgibin/sis/search2/f?./temp/2aMfLZ:2[19_TD$IF] on
Safety and Health (NIOSH). NIOSH January 22, 2015.
Pocket Guide to Chemical Hazards: 8. Still, K.; Jederberg, W.; Luttrell, W.
2-Butanone. Accessed from [10_TD$IF]http://www. Derivation of [20_TD$IF]occupational exposure
cdc.gov/niosh/npg/npgd0069.html[9_TD$IF] on Janu- limits, In Luttrell, W. E.; Jederberg, W.
ary 21, 2015. W.; Still, K. R. (Eds.), Toxicology
3. O’Neil, M. J.; Heckelman, P. E.; Koch, Principles for the Industrial Hygie-
C. B.; Roman, K. J. The Merck Index, nist, American Industrial Hygiene
14th ed[1_TD$IF]. Merck & Co: Whitehouse Association (AIHA): Fairfax, VA,
Station, NJ, 2006, pp. 1047–1048. 2008, p. 347.
4. Institut fur Arbeitsschutz der 9. Zenz, C.; Dickerson, O. B.; Horvath, E.
Deutschen Gesetzlichen Unfaliversi- P., Jr. Occupational Medicine, 3rd ed[1_TD$IF].
cherung (IFA). [12_TD$IF]GESTIS Substance Da- Mosby-Year Book, Inc.: St. Louis, MO,
tabase: Butanone[13_TD$IF]. Accessed from http:// 1994, p. 149.
gestis-en.itrust.de/nxt/gateway.dll/ 10. New Jersey Department of Health and
gestis_en/000000.xml?f=templates$fn= Senior Services. [2_TD$IF]Hazardous Substance
default.htm$vid=gestiseng:sdbeng$3.0[14_TD$IF] on Fact Sheet: Acetone[23_TD$IF]. Accessed from
January 21, 2015. http://nj.gov/health/eoh/rtkweb/documents/
5. American Conference of Governmen- fs/0006.pdf[24_TD$IF] on January 25, 2014.
tal Industrial Hygienists (ACGIH). 11. Lewis, Sr., ; Richard, J. Sax’s Danger-
[16_TD$IF]Documenta- tion of the ous Properties of Industrial Materials,
Threshold Limit Values for Chemical 8th ed[1_TD$IF]. Van Nostrand Reinhold: New
Substances: Methyl Ethyl Ketone, [17_TD$IF]7th York, NY, 1992, p. 2319.
ed. ACGIH: Cincinnati, OH, 2001, 12. Woo, Y.-T., ; Lai, D.; McLain, J. L.;
Accessed from http://www.acgih.org Manibusan, M. K.; Dellarco, V. Use of
on January 21, 2015. [25_TD$IF]mechanism-based structure–activity
6. U.S. Environmental Protection Agency relationships analysis in carcinogenic
(EPA). Toxicological Review of Methyl potential ranking for drinking water
Ethyl Ketone, dated September 2003. disinfection by-products. Environ.
Accessed from [10_TD$IF]http://www.epa.gov/iris[18_TD$IF] on Health Perspect. 2002, 110, 75–87.
January 21, 2015. 13. Bingham, E.; Cohrssen, B.; Powell, C.
7. National Library of Medicine (NLM). H. Patty’s Toxicology Volumes [26_TD$IF]1–9, 5th
Hazardous Substances Data Bank ed. John Wiley & Sons: New York,
(HSDB): Methyl Ethyl Ketone. Ac- N.Y, 2001.
cessed from [10_TD$ IF ]http://toxnet.nlm.nih.gov/
36 Journal of Chemical Health & Safety, July/August 2015
14. Milas, N. A.; Golubović, A. Studies in
[27_TD$IF]organic peroxides. XXV. Preparation,
[28_TD$IF]separation and identification of perox-
ides derived from methyl ethyl ketone
and hydrogen peroxide. J. Am. Chem.
Soc. 1959, 81(21), 5824–5826.
15. Zhang, J.; Wu, W.; Qian, G.; Zhou, X.
Continuous synthesis of methyl ethyl
ketone peroxide in a microreaction
system with concentrated hydrogen
peroxide. J. [29_TD$IF]Hazard. Mater. 2010, 181,
1024–1030.
16. Occupational Safety and Health Ad-
ministration (OSHA). [30_TD$IF]Sampling and
Analytical Methods: 2-butanone
(MEK) and Hexone (MIBK)[31_TD$IF]. Accessed
from https://www.osha.gov/dts/sltc/
methods/mdt/mdt1004/1004.html[9_TD$IF] on March
28, 2015.
17. American Conference of Governmen-
tal Industrial Hygienists (ACGIH).
[3_TD$IF]TLVs and BEIs Based on the Docu-
mentation of the Threshold Limit Va-
lues for Chemical Substances and
Physical Agents & Biological Exposure
Indices; ACGIH: Cincinnati, OH,
2014, p. 41.
18. Murnane, S. S.; Lehocky, A. H.;
Owens, P. D. Odor Thresholds for
Chemicals with Established Occupa-
tional Health Standards, 2nd ed[35_TD$IF][6.
American Industrial Hygiene Associa-
tion (AIHA): Falls Church, VA, 2013,
pp. 107–108.