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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 2
CCOHS Chemical Name: Methyl ethyl ketone

Synonyms:
2-Butanone
3-Butanone
Butanone
Ethyl methyl ketone
MEK
Methyl acetone
Methyl-2-propanone
Ethyl methyl cetone

Chemical Name French: Méthyl éthyl cétone
Chemical Name Spanish: Metiletilcetona
CAS Registry Number: 78-93-3
UN/NA Number(s): 1193
RTECS Number(s): EL6475000
EU EINECS/ELINCS Number: 201-159-0
Chemical Family: Saturated aliphatic ketone / alkanone
Molecular Formula: C4-H8-O
Structural Formula: CH3-CO-CH2-CH3

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless liquid; fresh or sweet/sharp, fragrant, acetone-like odour.(9)

Odour Threshold:
Range of values reported: 2-85 ppm (detection) (11); 5.4-55 ppm (recognition).(11)

Warning Properties:
NOT RELIABLE - Range of odour thresholds with high value (85 ppm) only one quarter of the TLV (200 ppm). Vapour has strong odour and irritating effects at 350 ppm.(27)

Uses and Occurrences:
The major use is as a solvent, particularly for various coating systems, such as vinyl, adhesives, nitrocellulose, and acrylic coatings; for paint removers, lacquers, varnishes, spray paints, sealers, glues, magnetic tapes, printing inks, resins, rosins, cleaning solutions, and polymerization. Used in dewaxing lubricating oils, degreasing of metals, in the production of synthetic leathers, transparent paper and aluminum foil, and as a chemical intermediate and catalyst. Extraction solvent in the processing of foodstuffs and food ingredients.(9,12,30) MEK is found in some fruits and vegetables and occurs naturally in blood, urine and exhaled air, probably as a minor product of normal metabolism.(9)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Colourless liquid with a sweet/sharp, fragrant, acetone-like odour. EXTREMELY FLAMMABLE LIQUID AND VAPOUR. Vapour is heavier than air and may spread long distances. Distant ignition and flashback are possible. Highly volatile. Irritating to eyes and respiratory tract. Central nervous system depressant. High vapour concentrations may cause headache, nausea, dizziness, drowsiness, incoordination and confusion. Causes eye irritation. Aspiration hazard. Swallowing or vomiting of the liquid may result in aspiration into the lungs.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Brief (3-5 minute) exposures to methyl ethyl ketone vapours produced slight nose and throat irritation at 100 ppm and definite nose and throat irritation at 350 ppm in approximately 10 people.(27) 143 volunteers exposed to 200 ppm for 4 hours reported throat irritation, unpleasant odour, nausea, and headache (in order of frequency reported).(19) Higher exposures are expected to cause central nervous system depression with symptoms such as headache, nausea, dizziness, drowsiness, and confusion. Extremely high concentrations may cause loss of consciousness and possibly death.
Neurobehavioural effects of exposures to methyl ethyl ketone (200 ppm for 4 hours) were studied with 137 volunteers. There were no statistically significant effects observed in biochemical, psychomotor, sensorimotor and psychological tests.(17,18) Similar findings have been reported in other studies.(19) Four volunteers were exposed to 90 to 270 ppm methyl ethyl ketone for 4 hours/day for 4 days. Minor disturbances in time perception were observed.(42)

Skin Contact:
Methyl ethyl ketone is expected to cause no or mild irritation. No irritation was produced when 20% methyl ethyl ketone in petrolatum was applied to volunteers for 48 hours in a closed patch test.(29) Animal studies indicate that methyl ethyl ketone is a mild skin irritant.

Eye Contact:
Animal evidence suggests that methyl ethyl ketone is a moderate to severe eye irritant. There is one human case report of an industrial splash of methyl ethyl ketone into the eye. The next day there was only slight eye irritation with no permanent injury. Later, severe inflammation of the eye developed which required intensive treatment. The author speculated that the delayed irritation may have been triggered by slight trauma.(26)
Methyl ethyl ketone vapour is irritating to the eyes. Brief (3-5 minutes) exposure to methyl ethyl ketone vapours produced mild eye irritation in some people at 200 ppm, while the majority experienced eye irritation at 350 ppm.(27) Momentary exposure to 3,300 and approximately 10,000 ppm produced intolerable eye irritation in men. 100 ppm was intolerable after "several inhalations" and 330 ppm was moderately irritating.(6)

Ingestion:
Unintentional, non-occupational ingestion of methyl ethyl ketone produced unconsciousness and hyperventilation in a woman. Severe lactic acidosis was apparent upon admission to the hospital but the authors were not certain whether methyl ethyl ketone or circulatory insufficiency caused this effect.(7) Ingestion of methyl ethyl ketone is expected to cause central nervous system depression with symptoms such as headache, nausea, dizziness, drowsiness, and confusion. Extremely high concentrations may cause loss of consciousness and possibly death.
Animal evidence suggests that methyl ethyl ketone can be aspirated (inhaled) into the lungs during ingestion or vomiting. Aspiration of even a small amount of liquid could result in a life threatening accumulation of fluid in the lungs. Severe lung damage (edema), respiratory failure, cardiac arrest and death may result.

Effects of Long-Term (Chronic) Exposure

Nervous System:
Epidemiological studies and case reports have shown nervous system effects in workers exposed to solvents, including methyl ethyl ketone, over a prolonged period of time.(22,43,44) It is not possible to associate the observed effects with any particular chemical.

Skin:
Repeated or prolonged contact can produce dermatitis (red, dry, itchy skin) and whitening of the skin.(22,29,31)

Skin Sensitization:
Methyl ethyl ketone is not an occupational skin sensitizer.
Despite extensive industrial use, there is only one case report of sensitization in a painter which was confirmed by positive response to standard patch testing with methyl ethyl ketone.(28) A maximization test using 20% methyl ethyl ketone in petrolatum produced no sensitization in 24 volunteers.(29)

Carcinogenicity:

A mortality study of 446 people who had worked at methyl ethyl ketone dewaxing plants concluded that there was no evidence of a cancer hazard. The average follow-up was 14 years. This study is limited by the small size of the cohort and the relatively short follow-up period.(32) Therefore, it is does not necessarily prove that methyl ethyl ketone is not a carcinogen. There is no other information available.

The International Agency for Research on Cancer (IARC) has not evaluated the carcinogenicity of this chemical.

The American Conference of Governmental Industrial Hygienists (ACGIH) has not assigned a carcinogenicity designation to this chemical.

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Teratogenicity and Embryotoxicity:
Some researchers have pointed to a concern that solvent exposure may have led to congenital defects in children born to female workers.(43,44) One of the solvents mentioned is methyl ethyl ketone, but is it not possible to implicate any particular solvent due to the extent of combined exposure. Animal studies have shown slight fetotoxicity (e.g. skeletal anomalies, reduced fetal weight) at concentrations that produced mild maternal toxicity.

Reproductive Toxicity:
No human or animal information available

Mutagenicity:
There is no human information available. In vivo animal studies, mammalian in vitro studies and virtually all short-term mutagenicity studies on test cell systems have been negative.(9,30,37,38)

Toxicologically Synergistic Materials:
There are several human case reports of neurological effects resulting from high exposure to methyl ethyl ketone in combination with other solvents.(15,16,22) Animal studies have confirmed synergism between methyl ethyl ketone and ethyl n-butyl ketone, methyl n-butyl ketone, n-hexane, carbon tetrachloride, 2,5- hexanedione and chloroform.(21,30,44) Principal target organs involved in toxicological interactions are the nervous system and liver, although the lung has also been implicated.(9,44)

Potential for Accumulation:
Methyl ethyl ketone does not accumulate in the body. It is rapidly absorbed by inhalation, skin contact and ingestion and transferred into the blood and other tissues. Methyl ethyl ketone is metabolized in the liver, mainly to 3-hydroxy-2- butanone and 2,3-butanediol which are eliminated in urine. Most methyl ethyl ketone probably enters the general metabolism in the body and is converted to acetate which is eventually broken down to carbon dioxide and water which are then eliminated in exhaled air and urine. Small amounts of methyl ethyl ketone itself are also eliminated in exhaled air and urine. Methyl ethyl ketone and its metabolites are mostly cleared from the body within 24 hours.(9)


SECTION 4. FIRST AID MEASURES

Inhalation:
This product is flammable. Take proper precautions (e.g. remove any sources of ignition). Remove source of contamination or move victim to fresh air. If breathing has stopped, trained personnel should begin artificial respiration (AR) or, if the heart has stopped, cardiopulmonary resuscitation (CPR) immediately. Obtain medical attention immediately.

Skin Contact:
As quickly as possible, flush with lukewarm, gently flowing water for at least 5 minutes or until the chemical is removed. Under running water, remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). If irritation persists, repeat flushing. Obtain medical advice immediately. Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 20 minutes or until the chemical is removed, while holding the eyelid(s) open. Take care not to rinse contaminated water into the unaffected eye or onto the face. Obtain medical attention immediately.

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness, is unconscious or is convulsing. DO NOT INDUCE VOMITING. Have victim drink 240 to 300 mL (8 to 10 oz.) of water to dilute material in stomach. If vomiting occurs naturally, have victim lean forward to reduce risk of aspiration. Repeat administration of water. Obtain medical attention immediately.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest). Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin contact.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
-9 deg C (16 deg F) (closed cup) (20); - 6 to -2 deg C (21 to 28 deg F) (closed cup) (9,12,21,23)

Lower Flammable (Explosive) Limit (LFL/LEL):
1.8% (23,24,25); 2% (12)

Upper Flammable (Explosive) Limit (UFL/UEL):
10% (23,30); 11.5% (24,25); 12.0% (21)

Autoignition (Ignition) Temperature:
404 deg C (759 deg F) (20); 515 deg C (960 deg F) (12,23)

Sensitivity to Mechanical Impact:
Insufficient information. Probably not sensitive, since it is a stable material.

Sensitivity to Static Charge:
Methyl ethyl ketone (MEK) will not accumulate static charge. The electrical conductivity of ketones is high. MEK vapours in the flammable range can probably be ignited by a static discharge.

Fire Hazard Summary:
Extremely flammable. Material will readily ignite at room temperature. Vapour is heavier than air and may travel a considerable distance to a source of ignition and flash back to a leak or open container. During a fire, irritating/toxic gases may be generated. Can accumulate in confined spaces, resulting in a toxicity and flammability hazard. Concentrated solutions in water may be flammable. Closed containers may rupture violently when heated.

Extinguishing Media:
Carbon dioxide, dry chemical powder, alcohol foam, polymer foam. Water may be ineffective because it will not cool MEK below its flash point.(23)

Fire Fighting Instructions:
Evacuate area and fight fire from a safe distance or protected location. Approach fire from upwind to avoid hazardous vapours and toxic decomposition products.
Stop leak before attempting to stop the fire. If the leak cannot be stopped, and if there is no risk to the surrounding area, let the fire burn itself out. If the flames are extinguished without stopping the leak, vapours could form explosive mixtures with air and reignite.
Because of the low flash point, water may be ineffective for fighting fires involving MEK. However, water can be applied as a fine spray to absorb the heat of the fire and to cool exposed containers and materials, and is capable of extinguishing the fire if used under favourable conditions and when hose streams are applied by experienced firefighters trained in fighting all types of flammable liquid fires.
If a leak or spill has not ignited, use water spray in large quantities to disperse the vapours, to protect personnel attempting to stop a leak. Water spray can be used to dilute spills to nonflammable mixtures and to flush spills away from ignition sources. Solid streams of water may be ineffective and spread material.
Closed containers may explode in the heat of the fire. Isolate materials not yet involved in the fire and protect personnel. Move containers from fire area if this can be done without risk. Keep fire-exposed tanks or containers cool by spraying with water to minimize the risk of rupture.
For a massive fire in a large area, use unmanned hose holder or monitor nozzles; if this is not possible withdraw from fire area and allow fire to burn. Stay away from ends of tanks. Withdraw immediately in case of rising sound from venting safety device or any discolouration of tank due to fire.
Firefighters may enter the area if positive pressure self-contained breathing apparatus (MSHA/NIOSH approved or equivalent) and full Bunker Gear is worn.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Health: 1 - Exposure would cause significant irritation, but only minor residual injury.
NFPA - Flammability: 3 - Liquids and solids that can be ignited under almost all ambient temperature conditions.
NFPA - Instability: 0 - Normally stable, even under fire conditions, and not reactive with water.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 72.11

Conversion Factor:
1 ppm = 2.94 mg/m3; 1 mg/m3 = 0.340 ppm at 25 deg C (calculated)

Physical State: Liquid
Melting Point: -86.3 deg C (-123.3 deg F) (12)
Boiling Point: 79.6 deg C (175.3 deg F) (9,12,21)
Relative Density (Specific Gravity): 0.805 at 20 deg C (water = 1) (9)
Solubility in Water: Soluble (26.8-29 mg/100 mL at 20 deg C) (9,24,43). Solubility also reported as 13.6 g/mL at 25 deg C (12)
Solubility in Other Liquids: Soluble in ethanol, acetone, diethyl ether, benzene, oils and other organic solvents (12,30)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 0.26 (9); 0.29 (9,12)
pH Value: Not available. Probably neutral.
Vapour Density: 2.41 (air = 1)
Vapour Pressure: 10.33 kPa (77.5 mm Hg) at 20 deg C (9,21)
Saturation Vapour Concentration: Approximately 102,000 ppm (10.2%) at 20 deg C (calculated)
Evaporation Rate: 2.7 (ether=1) (30)
Critical Temperature: 262.5 deg C (504.5 deg F) (30)

Other Physical Properties:
VISCOSITY: 0.41 mPa.s (0.41 centipoises) at 20 deg C (30)
SURFACE TENSION: 24.6 dynes/cm at 20 deg C (30)
CRITICAL PRESSURE: 4155 kPa (41 atm) (30)


SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable. May form peroxides, which may be explosive after prolonged exposure to air and heat and upon prolonged storage.(9)

Hazardous Polymerization:
Does not occur

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


OXIDIZING AGENTS (e.g. peroxides, nitrates, perchlorates) - increased risk of fire and explosion.(23,24)
STRONG ACIDS (e.g. oleum, chlorosulfonic acid) - reaction can produce heat and pressure.(20)
MIXTURES of HALOFORMS (e.g. chloroform) AND STRONG BASES (e.g. potassium hydroxide) - may react vigorously or explosively.(25)
MIXTURES of HYDROGEN PEROXIDE AND NITRIC ACID - may overheat and explode violently due to formation of shock- and heat-sensitive peroxides.(24,25)
SOLID POTASSIUM t-BUTOXIDE - contact with liquid or vapours of MEK can ignite after 0.5 to 1 minute.(20,25)
2-PROPANOL - MEK markedly increases the peroxidation of the alcohol in light and the mixture can explode on heating.(25)

Hazardous Decomposition Products:
Explosive peroxides, such as MEK peroxide

Conditions to Avoid:
Flames, sparks, electrostatic discharge, heat and other ignition sources.

Corrosivity to Metals:
Attacks copper in the presence of acetylene.(24)


SECTION 11. TOXICOLOGICAL INFORMATION

LC50 (male rat): 11700 ppm (4-hour exposure) (3)
LC50 (male rat): 11300 ppm (4-hour exposure); cited as 23.5 mg/L (7990 ppm) (8-hour exposure) (4)

LD50 (oral, adult male rat): 2740 mg/kg; cited as 3.4 mL/kg (1)

LD50 (dermal, rabbit): greater than 5000 mg/kg (29, unconfirmed)

Eye Irritation:

Application of 0.005 mL of undiluted methyl ethyl ketone to rabbit eyes produced severe irritation.(5) Application of pure, 30%, 10% and 1% solutions of methyl ethyl ketone in a standard Draize test using rabbits resulted in moderate/severe irritation for pure methyl ethyl ketone and mild irritation for all other concentrations.(10) In an interlaboratory comparison study, where eye irritation was evaluated in rabbits using a standard Draize test, 71% of the laboratories rated methyl ethyl ketone as an eye irritant (degree not specified).(8) The corneas of guinea pigs exposed to 10000 ppm vapour for 30 minutes or more became opaque. In some cases, this effect persisted for the 8 day observation period.(6)

Skin Irritation:

Application of 0.01 mL of undiluted methyl ethyl ketone to the clipped rabbit skin for 24 hours (uncovered) resulted in mild irritation.(5) Application of full strength methyl ethyl ketone to intact or abraded rabbit skin for 24 hours under occlusion was moderately irritating.(29) In an interlaboratory comparison study, where skin irritation was evaluated in rabbits by covered application of 0.5 mL to shaved skin for 24 hours, over 70% of the laboratories rated methyl ethyl ketone as a mild skin irritant.(8)

Effects of Short-Term (Acute) Exposure:

Inhalation:
Very high concentrations have produced irritation of the nose and eyes, followed by central nervous system depression with incoordination, unconsciousness, gasping respiration and death. Guinea pigs were exposed to 3300 to 100000 ppm for 13.5 hours. No abnormal signs were observed during or following exposure to 3300 ppm for 810 minutes. Exposure to 10000 ppm produced irritation (2-4 minutes), lacrimation (40 minutes), incoordination (90 minutes) and unconsciousness (240-280 minutes). Gasping respiration was produced during 20 and 180 minute exposures to 33000 and 100000 ppm. Death resulted from 45 and 200 minute exposures to 33000 and 100000 ppm. Slight congestion of the brain and marked congestion and emphysema of the lungs, liver and kidneys were observed in animals that died during exposure. Animals that survived subsequently recovered.(6) The concentration which reduced the respiratory rate of mice by 50% (RD50) was 10745 ppm (which was very high compared to other irritants tested).(36) This indicates that methyl ethyl ketone is a sensory irritant (causes burning and painful irritation of the nose and eyes) at very high concentrations.

Ingestion:
Exposure of mice in LD50 studies has resulted in incoordination, unconsciousness, respiratory depression and death.(2) Methyl ethyl ketone is easily aspirated into the lungs. When aspiration of methyl ethyl ketone was induced in 6 rats, there was a high mortality with rapid onset (4/6).(41)

Effects of Long-Term (Chronic) Exposure:

Inhalation:
Exposure to 5000 ppm for 13 weeks produced an exposure-related effect on body and liver weights in male and female rats, as well as a depression in brain weight in females.(13) Guinea pigs and rats were exposed to 235 ppm for 12 weeks (5 d/w, 7 h/d). There were no deaths nor signs of intoxication for rats. There were deaths in both control and experimental guinea pigs (2 in each group).(3) Extensive neurological studies with high exposures have shown no effects. In one study, rats were initially exposed to 10000 ppm which was reduced to 6000 ppm due to severe irritation of the upper respiratory tract. Temporary signs of muscle incoordination and gait disturbances were observed throughout the exposure. Exposures continued for only 7 of the planned 15 weeks since animals died of bronchopneumonia with no neurological symptoms.(16) In the other study, rats were exposed to 1125 ppm continuously for up to 55 days with no neurotoxicity.(15)

Skin Sensitization:
Methyl ethyl ketone did not produce sensitization in the mouse ear thickness test.(14)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
Methyl ethyl ketone has caused fetotoxic effects (minor skeletal variations, delayed bone formation, reduced fetal weight) in rats and mice in the presence of mild maternal toxicity. One rat study showed non-dose related fetotoxicity in the absence of maternal toxicity, and a low, but statistically significant, increased in malformations in the presence of mild maternal toxicity. These observations were not confirmed in later studies by the same researchers.
Rats were exposed by inhalation to 0, 1126 or 2618 ppm reagent grade methyl ethyl ketone on days 6-15 of pregnancy. Statistically significant fetotoxicity (reduced fetal weight and crown-rump length) was observed with exposure to 1126 ppm, but not 2618 ppm. There was no statistically significant teratogenicity (soft tissue or skeletal anomalies) or embryotoxicity (e.g. resorptions) observed. However, the total number of litters containing fetuses with skeletal anomalies was significantly increased with exposure to 1126 ppm. At 2618 ppm, in 4/21 litters (1 fetus/litter), there was a low, but statistically significant, increase in malformations and sternebral (e.g. delayed ossification) and total soft tissue anomalies were increased. Significant maternal toxicity was not observed at either exposure level, but food consumption was reduced during days 10-11 and 14-15 in animals exposed to 2618 ppm.(35) In subsequent studies, rats and mice were exposed by inhalation to 0, 400, 1000 or 3000 ppm methyl ethyl ketone (greater than 99% purity) during days 6-15 of pregnancy. There were no embryotoxic or teratogenic effects at any exposure level. At 3000 ppm, there were slight fetotoxic effects (minor skeletal variations; delayed bone formation; reduced fetal weight) with very slight maternal toxicity (decreased weight gain and increased water consumption in rats; increased relative liver weight in mice).(33,34)

Mutagenicity:
The available information does not indicate that methyl ethyl ketone is mutagenic.
Methyl ethyl ketone was not mutagenic in in vivo micronucleus assays with mice injected with 1.96 mL/kg (38) or hamsters injected with 411 mg/kg.(9) This route of exposure is not considered relevant to occupational situations.
Methyl ethyl ketone did not produce chromosomal aberrations or sister chromatid exchanges in Chinese hamster ovary cells.(30) It was not mutagenic in several cultured mammalian test systems in vitro, including human lymphocytes, both with and without metabolic activation.(30,37) Methyl ethyl ketone was not mutagenic in Salmonella typhimurium, Escherichia coli and Saccharomyces cerevisiae, both with and without metabolic activation.(21,30,38) In two other studies with Saccharomyces cerevisiae yeast, methyl ethyl ketone gave positive results.(39,40)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Kimura, E.T., et al. Acute toxicity and limits of solvent residue for sixteen organic solvents. Toxicology and Applied Pharmacology. Vol. 19 (1971). p. 699-704
(2) Zakhari, S., et al. Acute oral, intraperitoneal and inhalational toxicity in the mouse. In: Isopropanol and ketones in the environment. Edited by L. Golberg, CRC Press, 1977, 1977. p. 67-69
(3) La Bell, C.W., et al. The vapor toxicity of a composite solvent and its principal components. A.M.A. Archives of Industrial Health. Vol. 12 (1955). p. 623-627
(4) Pozzani, U.W., et al. The toxicological basis of threshold limit values: 5. The experimental inhalation of vapor mixtures by rats, with notes upon the relationship between single dose inhalation and single dose oral data. Industrial Hygiene Association Journal. Vol. 20 (October 1959). p. 364-369
(5) Smyth, Jr. H.F., et al. Range-finding toxicity data: List VI. American Industrial Hygiene Association Journal. Vol. 23 (March, 1962). p. 95-107
(6) Patty, F.A., et al. Acute response of guinea pigs to vapors of some new commercial organic compounds. VIII. Butanone. U.S. Public Health Service Reports. Vol. 50 (September 6, 1935). p. 1217-1228
(7) Kopelman, P.G., et al. Severe metabolic acidosis after ingestion of butanone. British Medical Journal. Vol. 286 (January 1, 1983). p. 21-22
(8) Weil, C.S., et al. Study of intra-and interlaboratory variability in the results of rabbit eye and skin irritation tests. Toxicology and Applied Pharmacology. Vol. 19, no. 2 (June, 1971). p. 276-360
(9) Methyl ethyl ketone. Environmental health criteria 143. World Health Organization, 1993
(10) Kennah II, H.E., et al. An objective procedure for quantitating eye irritation based upon changes of corneal thickness. Fundamental and Applied Toxicology. Vol. 12, no. 2 (February, 1989). p. 258-268
(11) Odor thresholds for chemicals with established occupational health standards. American Industrial Hygiene Association, 1989. p. 23, 67-68
(12) Toxicological profile for 2-butanone. (TP-91/08). Agency for Toxic Substances and Disease Registry, U.S. Public Health Service, July, 1992.
(13) Cavender, F.L., et al. A 90-day vapor inhalation toxicity study of methyl ethyl ketone. Fundamental and Applied Toxicology. Vol. 3, no. 7-8 (July/August 1983). p. 264-270
(14) Descotes, J. Identification of contact allergens: the mouse ear sensitization assay. Journal of Toxicology-Cutaneous & Ocular Toxicology. Vol. 7, no. 4 (December, 1988). p. 263-272
(15) Saida, K., et al. Peripheral nerve changes induced by methyl n-butyl ketone and potentiation by methyl ethyl ketone. Journal of Neuropathology and Experimental Neurology. Vol. 35, no. 3 (May/June, 1976). p. 207-225
(16) Altenkirch, H., et al. Experimental studies on hydrocarbon neuropathies induced by methyl-ethyl-ketone (MEK). Journal of Neurology. Vol. 219, no. 3 (1978). p. 159-170
(17) Dick, R.B., et al. Neurobehavioural effects of short duration exposures to acetone and methyl ethyl ketone. British Journal of Industrial Medicine. Vol. 46, no. 2 (February, 1989). p. 111-121
(18) Dick, R.B., et al. Effects of short duration exposures to acetone and methyl ethyl ketone. Toxicology Letters. Vol.43, no. 1-3 (October, 1988). p. 31-49
(19) Dick. R.B., et al. Neurobehavioural effects from acute exposures to methyl isobutyl ketone and methyl ethyl ketone. Fundamental and Applied Toxicology. Vol. 19, no. 3 (October, 1992). p. 453-473
(20) Fire protection guide to hazardous materials. 13th ed. Edited by A.B. Spencer, et al. National Fire Protection Association, 2002. NFPA 49; NFPA 491
(21) Topping, D.C., et al. Ketones. In: Patty's industrial hygiene and toxicology. Edited by G.D. Clayton, et al. 4th Edition. Volume II. Toxicology. Part C. John Wiley & Sons, Inc., 1994. p. 1739-1772, 1854- 1878
(22) Smith, A.R., et al. Study of poisoning and fire hazards of butanone and acetone. New York State Industrial Bulletin. Vol. 23 (April, 1944). p. 174-176
(23) The Sigma-Aldrich library of chemical safety data. Edition II. Vol. 1. Sigma-Aldrich Corporation, 1988. p. 606C
(24) Chemical safety sheets; working safely with hazardous chemicals. Kluwer Academic Publishers, 1991. p. 596
(25) Bretherick, L. Bretherick's handbook of reactive chemical hazards. 4th edition. Butterworths, 1990. p. 132, 391-392, 465, 474-475, 1208, 1843
(26) Berg, E.F. Retrobulbar neuritis: a case report of presumed solvent toxicity. Annals of Ophthamology. Vol. 3, no. 12 (1971). p. 1351-1353
(27) Nelson, K.W., et al. Sensory response to certain industrial solvent vapors. Journal of Industrial Hygiene and Toxicology. Vol.25, no. 7 (September, 1943). p. 282-285
(28) Varigos, G.A., et al. Contact urticaria from methyl ethyl ketone. Contact Dermatitis. Vol. 15, no 4 (October, 1986). p. 259-260
(29) Opdyke, D.L.J. Methyl ethyl ketone. Fragrance raw materials monographs. Food and Cosmetics Toxicology. Vol. 15, no. 6 (1977). p. 627- 632
(30) HSDB record for methyl ethyl ketone. Last revision date: 95/01/23
(31) Malten, K.E., et al. Horny layer injury by solvents. Occupational Dermatoses. Vol. 16, no. 3 (June, 1968). p. 135-147
(32) Alderson, M.R., et al. Mortality of workers on an isopropyl alcohol plant and two MEK dewaxing plants. British Journal of Industrial Medicine. Vol. 37, no. 1 (1980). p. 85-89
(33) Deacon, M.M., et al. Embryo- and fetotoxicity of inhaled methyl ethyl ketone in rats. Toxicology and Applied Pharmacology. Vol. 59, no. 3 (1981). p. 620-622
(34) Schwetz, B.A., et al. Developmental toxicity of inhaled methyl ethyl ketone in Swiss mice. Fundamental and Applied Toxicology. Vol. 16, no. 4 (May, 1991). p. 742-748
(35) Schwetz, B.A., et al. Embryo- and fetotoxicity of inhaled carbon tetrachloride, 1,1-dichloroethane and methyl ethyl ketone in rats. Toxicology and Applied Pharmacology. Vol. 28, no. 3 (June, 1974). p. 452- 464
(36) De Ceaurriz, J.C., et al. Sensory irritation caused by various industrial airborne chemicals. Toxicology Letters. Vol. 9, no. 2 (1981). p. 137-143
(37) Perocco, P., et al. Toxic activity of seventeen industrial solvents and halogenated compounds on human lymphocytes cultured in vitro. Toxicology Letters. Vol. 16, no. 1-2 (April, 1983). p. 69-75
(38) O'Donoghue, J.L., et al. Mutagenicity studies on ketone solvents: methyl ethyl ketone, methyl isobutyl ketone, and isophorone. Mutation Research. Vol. 206, no. 2 (October, 1988). p. 149-161
(39) Whittaker, S.G., et al. Detection of induced mitotic chromosome loss in Saccharomyces cerevisiae: an interlaboratory assessment of 12 chemicals. Mutation Research. Vol. 241, no. 3 (July, 1990). p. 225-242
(40) Zimmermann, F.K., et al. Acetone, methyl ethyl ketone, ethyl acetate, acetonitrile and other polar aprotic solvents are strong inducers of aneuploidy in Saccharomyces cerevisiae. Mutation Research. Vol. 149 (1985). p. 339-351
(41) Panson, R.D, et al. Aspiration toxicity of ketones. Clinical Toxicology. Vol. 17, no. 2 (1980). p. 271-317
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Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 1995-05-31

Revision Indicators:
Respiratory guidelines 1995-08-01
EU number 1995-08-01
Sensitivity to static charge 1995-10-01
Handling 1995-10-01
TLV comments 1995-10-01
Ingestion (health) 1997-12-01
US transport 1998-03-01
Bibliography 2000-04-01
EU Class 2000-04-01
EU Risk 2000-04-01
EU Safety 2000-04-01
EU Comments 2000-04-01
PEL transitional comments 2003-11-06
PEL-TWA final 2003-11-06
PEL-STEL final 2003-11-06
Resistance of materials for PPE 2004-03-29
Toxicological info 2005-01-19
Teratogenicity/embryotoxicity 2005-01-19
WHMIS detailed classification 2005-01-19
WHMIS proposed classification 2005-01-19
WHMIS disclosure list 2005-01-19
WHMIS health effects 2005-01-19
OSHA hazcom 2005-01-19
Emergency overview 2005-01-19
Bibliography 2005-03-14
Sampling/analysis 2005-03-14
Handling 2005-03-29



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