IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
Health and Safety Guide No. 58
METHYL ISOBUTYL KETONE
HEALTH AND SAFETY GUIDE
UNITED NATIONS ENVIRONMENT PROGRAMME
INTERNATIONAL LABOUR ORGANISATION
WORLD HEALTH ORGANIZATION
WORLD HEALTH ORGANIZATION, GENEVA 1991
This is a companion volume to Environmental Health Criteria 117:
Methyl isobutyl ketone
Published by the World Health Organization for the International
Programme on Chemical Safety (a collaborative programme of the United
Nations Environment Programme, the International Labour Organisation,
and the World Health Organization)
This report contains the collective views of an international group of
experts and does not necessarily represent the decisions or the stated
policy of the United Nations Environment Programme, the International
Labour Organisation, or the World Health Organization
WHO Library Cataloguing in Publication Data
Methyl isobutyl ketone : health and safety guide.
(Health and safety guide ; no. 58)
1. Ketones - standards I. Series
ISBN 92 4 151058 7 (NLM Classification: QV 633)
ISSN 0259-7268
(c) World Health Organization 1991
Publications of the World Health Organization enjoy copyright
protection in accordance with the provisions of Protocol 2 of the
Universal Copyright Convention. For rights of reproduction or
translation of WHO publications, in part or in toto, application
should be made to the Office of Publications, World Health
Organization, Geneva, Switzerland. The World Health Organization
welcomes such applications.
The designations employed and the presentation of the material in this
publication do not imply the expression of any opinion whatsoever on
the part of the Secretariat of the World Health Organization
concerning the legal status of any country, territory, city or area or
of its authorities, or concerning the delimitation of its frontiers or
boundaries.
The mention of specific companies or of certain manufacturers'
products does not imply that they are endorsed or recommended by the
World Health Organization in preference to others of a similar nature
that are not mentioned. Errors and omissions excepted, the names of
proprietary products are distinguished by initial capital letters.
CONTENTS
INTRODUCTION
1. PRODUCT IDENTITY AND USES
1.1. Identity
1.2. Physical and chemical properties
1.3. Analytical methods
1.4. Uses
2. SUMMARY AND EVALUATION
2.1. Human exposure to MIBK
2.2. Uptake, metabolism, and excretion
2.3. Effects on animals
2.4. Effects on human beings
3. CONCLUSIONS AND RECOMMENDATIONS
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1. Main human health hazards, prevention and protection, first
aid
4.1.1. Advice to physicians
4.1.1.1 Symptoms of poisoning
4.1.1.2 Medical advice
4.1.2. Health surveillance advice
4.2. Safety in use
4.3. Explosion and fire hazards
4.3.1. Flammability and explosion
4.3.2. Fire
4.4. Storage
4.5. Transport
4.6. Spillage and disposal
4.6.1. Spillage
4.6.2. Disposal
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
6. SUMMARY OF CHEMICAL SAFETY INFORMATION
7. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
7.1. Regulation of emissions
7.2. Regulation of food and food wrappings
7.3. Regulation of beverages
7.4. Exposure limit values
7.5. Labelling and packaging
BIBLIOGRAPHY
INTRODUCTION
The Environmental Health Criteria (EHC) documents produced by the
International Programme on Chemical Safety include an assessment of
the effects on the environment and on human health of exposure to a
chemical or combination of chemicals, or physical or biological
agents. They also provide guidelines for setting exposure limits.
The purpose of a Health and Safety Guide is to facilitate the
application of these guidelines in national chemical safety
programmes. The first three sections of a Health and Safety Guide
highlight the relevant technical information in the corresponding EHC.
Section 4 includes advice on preventive and protective measures and
emergency action; health workers should be thoroughly familiar with
the medical information to ensure that they can act efficiently in an
emergency. Within the Guide is a Summary of Chemical Safety
Information which should be readily available, and should be clearly
explained, to all who could come into contact with the chemical. The
section on regulatory information has been extracted from the legal
file of the International Register of Potentially Toxic Chemicals
(IRPTC) and from other United Nations sources.
The target readership includes occupational health services, those in
ministries, governmental agencies, industry, and trade unions who are
involved in the safe use of chemicals and the avoidance of
environmental health hazards, and those wanting more information on
this topic. An attempt has been made to use only terms that will be
familiar to the intended user. However, sections 1 and 2 inevitably
contain some technical terms. A bibliography has been included for
readers who require further background information.
Revision of the information in this Guide will take place in due
course, and the eventual aim is to use standardized terminology.
Comments on any difficulties encountered in using the Guide would be
very helpful and should be addressed to:
The Manager
International Programme on Chemical Safety
Division of Environmental Health
World Health Organization
1211 Geneva 27
Switzerland
THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING POINT
TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME
1. PRODUCT IDENTITY AND USES
1.1 Identity
Common name: methyl isobutyl ketone (MIBK)
Chemical structure
CH3
'
CH3 - C - CH2 - CH
" '
O CH3
Chemical formula: C6H12O
Relative molecular mass: 100.16
CAS chemical name: 4-methyl-2-pentanone
CAS registry number: 108-10-1
RTECS registry number: SA9275000
Purity: MIBK is typically 99% (w/w) pure.
Impurities that may be present include:
dimethyl heptane (0.3%), water (0.1%),
methyl isobutyl carbinol (0.06%),
mesityl oxide (0.03%), acetic acid
(0.002%), and non-volatile components
(0.002%).
1.2 Physical and Chemical Properties
MIBK is a clear liquid with a sweet odour; the odour threshold is
1.64 mg/m3 (0.4 ppm). It is moderately soluble in water.
Some physical and chemical properties of MIBK are given in the Summary
of Chemical Safety Information (section 6).
MIBK can react violently with oxidizing and reducing agents. When
heated, peroxides may form by auto-oxidation and may explode
spontaneously.
1.3 Analytical Methods
Gas chromatography combined with flame ionization or mass spectroscopy
is a suitable technique for the determination of MIBK, which can be
detected in air (by trapping with, e.g., charcoal), in water (e.g.,
headspace or extraction), and in biological tissues (e.g., headspace
or extraction).
1.4 Uses
MIBK, which occurs naturally in food, is a permitted flavouring agent
and is used in food-contact materials. It is a component of cellulose
and polyurethane lacquers and paint solvents. It is also used: as an
extraction solvent; in the manufacture of methyl amyl alcohol; and as
a denaturant for ethyl alcohol.
2. SUMMARY AND EVALUATION
2.1 Human Exposure to MIBK
The general population is exposed to low levels of MIBK, which has
been detected in certain foods at levels in the mg/kg range. Two
countries have established maximum ambient air concentrations in the
range of 0.1-0.2 mg/m3 for general population exposure.
Occupational exposure occurs particularly in the production and use of
lacquers, paints, and extraction solvents. The major route of
exposure is inhalation.
2.2 Uptake, Metabolism, and Excretion
MIBK is absorbed in animals via inhalation, ingestion, and through the
skin. It is widely distributed throughout the body. MIBK is readily
metabolized to water-soluble excretory products and can induce
metabolic activation in the liver. The urine is the major route of
excretion for metabolites.
2.3 Effects on Animals
In animal studies, the acute systemic toxicity of MIBK, via the oral
and inhalation routes of exposure, is low. In a 90-day gavage study
on rats, a no-observed-effect level (NOEL) of 50 mg/kg per day was
found. In 90-day inhalation studies on rats and mice, concentrations
of up to 4100 mg/m3 (1000 ppm) did not result in significant
toxicity, though compound-related reversible morphological changes
were reported in the liver and kidney. Evidence of central nervous
system depression was seen in animals exposed to a level of
4100 mg/m3 (1000 ppm). In a number of studies, exposure to MIBK
concentrations as low as 1025 mg/m3 (250 ppm) resulted in an
increase in liver size and induced hepatic microsomal metabolism.
This may be responsible for the exacerbation of haloalkane toxicity
and for the potentiation of the neurotoxicity of n-hexane. MIBK was
also found to potentiate the cholestatic effects of manganese given
with, or without, bilirubin. In 90-day studies on mice, rats, dogs,
and monkeys, only male rats developed hyaline droplets in the proximal
tubules of the kidney. Effects on behaviour were reported in baboons
exposed for 7 days to 205 mg/m3 (50 ppm).
At a concentration of 4100 mg/m3 (1000 ppm), MIBK was not
embryotoxic, fetotoxic, or teratogenic in rats or mice. Fetotoxicity
was only observed at concentrations of MIBK that caused maternal
toxicity.
MIBK did not induce gene mutations in in vitro bacterial test
systems with, or without, metabolic activation. Negative results were
also obtained in vitro with, or without, metabolic activation, in
tests for mitotic gene conversion in yeast, and for gene mutation in
cultured mammalian cells. The results of in vitro assays for
unscheduled DNA synthesis in primary rat hepatocytes and for
structural chromosome damage in cultured rat liver cells were
negative. An in vivo micronucleus test on mice was negative. These
data indicate that MIBK is not genotoxic. No long-term or
carcinogenicity studies are available.
The toxicity of MIBK for aquatic organisms and microorganisms is low.
2.4 Effects on Human Beings
The low odour threshold (1.64 mg/m3) and the irritant effects can
provide warning of high concentrations. Exposure to levels of
10-410 mg/m3 (2.4-100 ppm) produced perceptible irritation of the
eyes, nose, or throat, and 820 mg/m3 (200 ppm) produced discomfort.
Symptoms, such as headache, nausea, or vertigo, also occurred at
10-410 mg/m3 (2.4-100 ppm). A 2-h exposure of up to 200 mg/m3
(50 ppm) did not produce any significant effects on a simple
reaction-time task or a test of mental arithmetic.
3. CONCLUSIONS AND RECOMMENDATIONS
Because of the irritant effects of MIBK, contact with the skin and
eyes should be avoided. Ingestion of MIBK should not occur with good
practices; workers who come into contact with MIBK should not be at
risk, provided that exposure levels in the workplace are kept as low
as possible and within the prescribed control limits.
The half-life of MIBK in the environment is short and its toxicity for
aquatic organisms is low. Consequently, there is no risk for the
environment, provided that there are adequate controls on disposal.
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1 Main Human Health Hazards, Prevention and Protection, First Aid
MIBK causes eye and respiratory tract irritation and has reversible
depressant effects on the central nervous system.
The hazards can be avoided by taking the appropriate precautions and
by controlling exposure.
4.1.1 Advice to physicians
4.1.1.1 Symptoms of poisoning
Symptoms and signs include: irritation of the eyes, skin, and
respiratory tract, and depression of the central nervous system,
manifested by headaches, nausea, and narcosis. Gastrointestinal pain
and hepatic toxicity may occur with exposure to high concentrations.
4.1.1.2 Medical advice
In case of poisoning by MIBK, contact the nearest Poisons Information
Centre for detailed advice on treatment. Information on first aid is
provided in the Summary of Chemical Safety Information. If breathing
ceases or becomes weak and irregular, artificial respiration should be
applied and oxygen administered. If there has been ingestion,
vomiting should not be induced, because of the risk of aspiration into
the lungs and the production of chemical pneumonitis. Gastric lavage
can be given if a cuffed endotracheal tube is used.
4.1.2 Health surveillance advice
A pre-employment medical examination is advised for workers who will
be regularly exposed to MIBK. If routine medical checks are
undertaken, emphasis should be placed on examination of the central
nervous system, respiratory tract, gastrointestinal tract, and skin.
4.2 Safety in Use
Air levels should be kept as low as practicable using suitably
designed plant and engineering controls, such as local exhaust
ventilation. Respiratory protection should be readily available for
use in enclosed spaces, and for certain maintenance operations.
Self-contained breathing apparatus should be available for use in
emergencies. Skin and eye protection is recommended, when exposure to
liquid MIBK is likely to occur.
4.3 Explosion and Fire Hazards
4.3.1 Flammability and explosion
MIBK is highly flammable and adequate ventilation should be provided.
Smoking should be prohibited and electrical equipment should be
designed to a recognized, explosion-proof standard.
4.3.2 Fire
Fire extinguishers containing carbon dioxide, dry powder, or foam are
recommended. Flashback along a vapour trail may occur. Water should
not be used, since this may cause the fire to spread, though a water
spray can be used to cool containers.
4.4 Storage
Drums should be stored in a well-ventilated area away from sources of
ignition and heat. The storage temperature should not exceed 40°C.
4.5 Transport
Comply with national and international requirements regarding the
transport of hazardous material. Containers should be in good
condition and properly labelled. Keep containers in a well-ventilated
place, away from sources of ignition. When pumping, the flow of MIBK
may generate electrostatic charges and, therefore, all equipment
should be earthed.
4.6 Spillage and Disposal
4.6.1 Spillage
In the event of spillage, naked flames, sparks, and heat should be
avoided. Contact with skin and eyes should be avoided by wearing
suitable protective gloves, face-shield and boots. Liquid should be
prevented from entering drains and sewers. Spillages (small-scale)
should be absorbed on paper towels, sawdust, or sand, and all material
should be removed to a safe place for subsequent disposal.
4.6.2 Disposal
The International Register of Potentially Toxic Chemicals recommends:
"Incineration, open burning, use as a boiler fuel. Spray into the
furnace. Incineration will become easier by mixing with a more
flammable solvent."
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
Industrial discharges from the manufacture, formulation, and technical
applications of MIKB should be controlled.
MIBK has a short half-life in the atmosphere and is also biodegraded
in water. It is not expected to bioaccumulate.
The toxicity of MIBK for microorganisms and aquatic organisms is low.
6. SUMMARY OF CHEMICAL SAFETY INFORMATION
This summary should be easily available to all health workers
concerned with, and users of, methyl isobutyl ketone. It should be
displayed at, or near, entrances to areas where there is potential
exposure to methyl isobutyl ketone, and on processing equipment and
containers. The summary should be translated into the appropriate
language(s). All persons potentially exposed to the chemical should
also have the instructions in the summary clearly explained.
Space is available for insertion of the National Occupational
Exposure Limit, the address and telephone number of the National
Poison Control Centre, and local trade names.
METHYL ISOBUTYL KETONE (MIBK)
CAS name: 4-methyl-2-pentanone Chemical formula: C6H12O
CAS registry number: 108-10-1 RTECS registry number: SA9275000
PHYSICAL PROPERTIES OTHER CHARACTERISTICS
Boiling point (C) 116 Colourless, volatile liquid with a sweet odour;
Freezing point (C) -80 odour threshold approximately 1.6 mg/m3 (0.4 ppm)
Specific gravity (20°C/4°C) 0.8017
Vapour pressure (KPa; 20°C) 1.99
Relative molecular mass 100.16
n-Octanol/water partition
coefficient (low Pow) 1.38
Solubility in water
(g/litre; 20°C) 17
Vapour density (air = 1) 3.45
Autoignition temperature (°C) 460
Explosion limits in air
(% by volume) 1.4-7.5
Closed-cup flashpoint (°C) 14
HAZARDS/SYMPTOMS PREVENTION AND PROTECTION FIRST AID
Vapour/fumes
SKIN: MIBK liquid may irritate Avoid skin contact; wear protective Remove from exposure; remove contaminated
the skin, when in close contact; clothing clothing; wash skin thoroughly with soap
repeated contact may produce and plenty of water
dermatitis because of its defatting
properties
EYES: Undiluted MIBK is an Wear face-shield or goggles Remove from exposure; irrigate the eyes
irritant; high vapour concentrations thoroughly with water or eyewash solution for
are irritant 15 minutes; obtain medical attention
INHALATION: MIBK at high Control work environment to within Remove patient to fresh air and keep warm;
concentrations is a respiratory recommended exposure limit; if breathing has stopped, apply artificial
irritant; it may cause depression otherwise provide respiratory respiration; obtain medical attention
of the central nervous system, protection, such as a respirator
such as dizziness, fatigue, and
nausea
INGESTION: should not occur Do not eat, drink, or smoke during Rinse mouth; vomiting should not be induced;
with good work practices work keep patient warm and rested; obtain medical
attention
ENVIRONMENT: half-life in Industrial discharges should be
the environment is short; low minimized and regulated;
toxicity for microorganisms and disposal should only be via
aquatic organisms; should not incineration
pose a risk, provided there are
adequate controls to minimize
emissions
SPILLAGE STORAGE FIRE AND EXPLOSION
Take appropriate personal Store drums in a well-ventilated Adequate ventilation should be provided
precautions; absorb spillage on area in fire-resistant containers; and there should be no sources of sparks,
paper towel, sawdust, or sand, for metal containers should be heat, or naked flames; flashback along a
subsequent action; avoid spills electrically-grounded, when vapour trail may occur; fire extinguishers
entering drains or surface waters transferring liquid containing carbon dioxide, dry powder,
or foam are recommended; water sprays
should not be used, except to cool containers
WASTE DISPOSAL LABELLING
Waste material should be National Occupational Exposure United Nations 1245
incinerated in an approved Limit: Hazard Class 3 (flammable liquid)
manner Packing Group III (medium danger)
National Poison Control Centre:
Local trade names:
7. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
The information given in this section has been extracted from the
International Register of Potentially Toxic Chemicals (IRPTC) legal
file. A full reference to the original national document from which
the information was extracted can be obtained from IRPTC. When no
effective date appears in the IRPTC legal file, the year of the
reference from which the data are taken is indicated by (r).
The reader should be aware that regulatory decisions about chemicals,
taken in a certain country, can only be fully understood in the
framework of the legislation of that country. The regulations and
guidelines of all countries are subject to change and should always be
verified with appropriate regulatory authorities before application
7.1 Regulation of Emissions
In the Federal Republic of Germany, MIBK belongs to Class III, the air
emissions of which must not exceed (as the sum of all compounds in any
class) 150 mg/m3 (37 ppm), at a mass flow of > 3 kg/h. The
maximum recommended ambient concentration is 0.2 mg/m3 (0.05 ppm) in
Czechoslovakia, and it must not exceed 0.1 mg/m3 (0.025 ppm) in the
USSR.
7.2 Regulation of Food and Food Wrappings
MIBK is allowed as a component of food-packaging materials in the EEC
and in the USA.
7.3 Regulation of Beverages
The Council of Europe Committee of Experts on Flavouring Substances
suggested a limit of 5 mg/litre in beverages.
7.4 Exposure Limit Values
Some occupational air exposure limit values are given in the table on
pages 24-26.
7.5 Labelling and Packaging
The United Nations recommends labelling as Hazard Class 3 (flammable
liquid), Packing Group III (medium danger).
In the European Economic Community, MIBK is labelled as follows:
Highly flammable, keep container in a well-ventilated place,
keep away from sources of ignition, no smoking, do not breathe
gas/fumes/vapour spray. Take precautionary measures against
static discharges.
OCCUPATIONAL AIR EXPOSURE LIMITS
Country/ Exposure limit descriptiona Value Effective
organization (mg/m3) dateb
Australia Recommended threshold limit value (TLV)
-Time weighted average (TWA) 205 1983(r)
-Short-term exposure limit (STEL) 300
Belgium Recommended threshold limit value (TLV)
-Time weighted average (TWA) 205 1988(r)
-Short-term exposure limit (STEL) 300
Finland Permissible exposure limit (MPC)
-Time weighted average(TWA) 210 1987
-Short-term exposure limit (STEL) 315
Germany (Federal Recommended threshold limit value (MAK)
Republic of) -Time weighted average (TWA) 400 1988(r)
-Short-term exposure limit (STEL) 2000
Japan Administrative concentration
-Time weghted average (TWA) 205 1990(n)
Netherlands Recommended threshold limit value (MXL)
-Time weighted average (TWA) 240 1989(r)
Poland Permissible exposure limit (MPC)
-Time weighted average (TWA) 200 1982(r)
Romania Permissible exposure limit (MPC)
-Time weighted average (TWA) 200 1984(r)
-Ceiling value (CLV) 300
Switzerland Permissible exposure limit (MAK)
-Time weighted average (TWA) 205 1987(r)
Country/ Exposure limit descriptiona Value Effective
organization (mg/m3) dateb
Sweden Permissible exposure limit (HLV)
-Time weighted average (TWA) 100 1990(n)
-Short-term exposure limit (STEL) 200
United Kingdom Occupational exposure standard (OES)
-Time weighted average (TWA) 205 1990(n)
-Short-term exposure limit (STEL) 300
USA (ACGIH) Recommended threshold limit value (TLV)
-Time weighted average (TWA) 205 1989
-Short-term exposure limit (STEL) 307
USA (OSHA) Permissible exposure limit (PEL)
-Time weighted average (TWA) 410 1974
USSR Temporary exposure limit (TSEL)
-Ceiling value (CLV) 5 1989
Yugoslavia Permissible exposure limit (MAC)
-Time weighted average (TWA) 410 1971(r)
a TWA = a maximum mean exposure limit, generally, over the period of a working day.
STEL = a maximum concentration of exposure for a specified time duration (generally 10-30 min).
b n = Notified direct by country.
BIBLIOGRAPHY
ACGIH (1986) Documentation of the threshold limit values and
biological exposure indices. Cincinnati, American Conference of
Governmental Industrial Hygienists.
ACGIH (1989) Threshold limit values and biological exposure indices
for 1989-1990. Cincinnati, American Conference of Governmental
Industrial Hygienists.
CLAYTON, G.D. & CLAYTON, F.E. (1981) Patty's industrial hygiene and
toxicology. Vol. 2 C. New York, Wiley-Interscience, John Wiley &
Sons.
GOSSELIN, R.E., HODGE, H.C., SMITH R.P., & GLEASON, M.N. (1976)
Clinical toxicology of commercial products. 4th ed. Baltimore,
Maryland, The Williams and Wilkins Company.
HANDLING CHEMICALS SAFELY (1989) Handling chemicals safely. 2nd ed.
Dutch Association of Safety Experts, Dutch Chemical Industry
Association, Dutch Safety Institute.
IRPTC (1988) Data profile (legal file). Geneva, International
Register of Potentially Toxic Chemicals.
SAX, N.I. (1984) Dangerous properties of industrial materials. New
York, Van Nostrand Reinhold Company.
US NIOSH (1976) A guide to industrial respiratory protection. 3 Vol.
Cincinnati, Ohio, US National Institute for Occupational Safety and
Health. Occupational Safety and Heath Administration,
US NIOSH/OSHA (1981) Occupational health guidelines for chemical
hazards. 3 Vol. Washington, DC, US Department of Health and Human
Services, US Department of Labor (Publication No. DHHS(NIOSH) 81-123).
US NIOSH/OSHA (1985) Pocket guide to chemical hazards. Washington
DC, US National Institute for Occupational Safety and Health,
Occupational Safety and Heath Administration (Publication No. 85.114).
WHO (1990) Environmental Health Criteria 117: Methyl isobutyl ketone.
Geneva, World Health Organization.
See Also:
Toxicological Abbreviations
Methyl isobutyl ketone (EHC 117, 1990)
Methyl isobutyl ketone (ICSC)