Hazard Summary

• Acute (short-term) exposure to methyl ethyl ketone in humans, via inhalation, results in irritation to the eyes, nose, and throat, and central nervous system depression.
• Limited information is available on the chronic (long-term) effects of methyl ethyl ketone in humans. Chronic inhalation studies in animals have reported effects on the central nervous system, liver, and respiratory system.
• The Reference Concentration (RfC) for methyl ethyl ketone is 1.0 mg/m³.^a The U.S. Environmental Protection Agency (EPA) estimates that inhalation of this concentration or less, over a lifetime, would not likely result in the occurrence of chronic, noncancer effects.^b
• The Reference Dose (RfD) for methyl ethyl ketone is 0.6 mg/kg/d.^c EPA estimates that consumption of this level or less, over a lifetime, would not likely result in the occurrence of chronic, noncancer effects.
• No information is available on the developmental or reproductive effects of methyl ethyl ketone in humans. Reduction of fetal development and fetal malformations has been reported in mice exposed to methyl ethyl ketone in the air.
• Limited data are available on the carcinogenic effects of methyl ethyl ketone. No human data are available and the only available animal study did not report skin tumors from dermal exposure to methyl ethyl ketone. EPA has classified methyl ethyl ketone as a Group D, not classifiable as to human carcinogenicity.

^a Milligrams per cubic meter is the unit of measurement for chemicals in air.
^b The RfC is not a direct estimator of risk, but rather a reference point to gauge the potential effects. Exceedance of the RfC does not imply that an adverse health effect would necessarily occur. As the amount and frequency of exposures exceeding the RfC increase, the probability that adverse health effects may be seen also increases.
^c Milligrams per kilogram per day is one way to measure the amount of the contaminant that is consumed in food.

Please Note: The main sources of information for this fact sheet are EPA's Health Effects Assessment for Methyl Ethyl Ketone and EPA's Integrated Risk Information System (IRIS), which contains information on inhalation chronic toxicity of methyl ethyl ketone and the RfC and oral chronic toxicity and the RfD. Other secondary sources include the Hazardous Substances Data Bank (HSDB), a database of summaries of peer-reviewed literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Environmental/Occupational Exposure

• Methyl ethyl ketone has been detected in both indoor and outdoor air. Methyl ethyl ketone can be produced in outdoor air by the photooxidation of certain air pollutants, such as butane and other hydrocarbons. (1)
• Methyl ethyl ketone has been found in drinking water and surface water at a number of sites. (2)
• Exposure to methyl ethyl ketone could also occur at the workplace and through exposure to household products containing the chemical. (1)

Assessing Personal Exposure

• Levels of methyl ethyl ketone in the urine can be measured to determine exposure to the chemical. (1)

Health Hazard Information

• Acute exposure to high concentrations of methyl ethyl ketone in humans produces irritation to the eyes, nose, and throat. (1,3,4)
• Other effects reported from acute inhalation exposure in humans include central nervous system depression, headache, and nausea. (1,3,4)
• Dermatitis has been reported in humans following dermal exposure to methyl ethyl ketone. (1)
• Tests involving acute exposure of animals, such as the LD₅₀ test in rabbits, has shown methyl ethyl ketone to have high acute toxicity from dermal exposure, while the LD₅₀ test in rats and mice has shown the chemical to have moderate toxicity from ingestion. (5)
• The LC₅₀ test in rats has indicated low toxicity from methyl ethyl ketone exposure via inhalation. (5)

Chronic Effects (Noncancer):

• Limited information is available on the chronic effects of methyl ethyl ketone in humans from inhalation exposure. One study reported nerve damage in individuals who sniffed a glue thinner containing methyl ethyl ketone and other chemicals. (1)
• Slight effects on the central nervous system, liver, and respiratory system have been reported in chronic inhalation studies of methyl ethyl ketone in animals. (1)
• The RfC for methyl ethyl ketone is 1 mg/m³ based on decreased fetal birth weight in mice. (6)
• EPA has medium confidence in the principal study on which the RfC is based because it is well designed and tested several exposure concentrations and several endpoints of toxicity although there are insufficient data presented for possible respiratory effects; low confidence in the database because there are no multigenerational studies and only one subchronic study and portal-of-entry effects are not adequately address; and, consequently, confidence in the RfC is low. (6)
• The RfD for methyl ethyl ketone is 0.6 mg/kg/d based on decreased fetal birth weight in rats. (6)
• EPA has low confidence in the study on which the RfD is based because lowering the high-dose group from 3.0 to 2.0% confounded determination of the critical effect; low confidence in the database because of the lack of oral data for MEK itself and the absence of data in a second species; and, consequently, low confidence in the RfD. (6)
• EPA's Office of Air Quality Planning and Standards, for a hazard ranking under Section 112(g) of the Clean Air Act Amendments, has evaluated methyl ethyl ketone for chronic toxicity and has given it a composite score of 10 (scores range from 1 to 100, with 100 being the most toxic). These scores are nonlinear and are the product of two ratings: a rating based on the minimal-effect dose and a rating based on the type of effect. (9)

Reproductive/Developmental Effects:

• No information on the reproductive or developmental effects of methyl ethyl ketone in humans was located.
• An inhalation study in mice reported retardation of fetal development and fetal malformations in animals exposed to methyl ethyl ketone. (4)

Cancer Risk:

• No information on the carcinogenicity of methyl ethyl ketone in humans was located.
• No studies were available on the carcinogenicity of methyl ethyl ketone by the oral or inhalation routes. In a dermal carcinogenicity study, skin tumors were not reported from methyl ethyl ketone exposure. (1,6)
• EPA has classified methyl ethyl ketone as a Group D, not classifiable as to human carcinogenicity, based on a lack of data concerning carcinogenicity in humans and animals. (6)

Physical Properties

• Methyl ethyl ketone is a colorless volatile liquid that is soluble in water. (2)
• The odor threshold for methyl ethyl ketone is 5.4 ppm, with an acetone-like odor reported. (8)
• The chemical formula for methyl ethyl ketone is C₄H₈O and the molecular weight is 72.10 g/mol. (9)
• The vapor pressure for methyl ethyl ketone is 95.1 mm Hg at 25 C, and it has a log octanol/water partition coefficient (Log K_ow) of 0.261. (9)

Uses

• The primary use of methyl ethyl ketone is as a solvent in processes involving gums, resins, cellulose acetate, and cellulose nitrate. (1)
• Methyl ethyl ketone is also used in the synthetic rubber industry, in the production of paraffin wax, and in household products such as lacquer and varnishes, paint remover, and glues. (1)

ACGIH STEL--American Conference of Governmental and Industrial Hygienists' short-term exposure limit: 15-min time-weighted-average exposure that should not be exceeded at any time during a workday even if the 8-h time-weighted-average is within the threshold limit value.
ACGIH TLV--American Conference of Governmental and Industrial Hygienists' threshold limit value expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effects.
LC₅₀ (Lethal Concentration₅₀)--A calculated concentration of a chemical in air to which exposure for a specific length of time is expected to cause death in 50% of a defined experimental animal population.
LOAEL--Lowest-observed-adverse-effect level.
NIOSH REL--National Institute of Occupational Safety and Health's recommended exposure limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure and/or ceiling.
NOAEL--No-observed-adverse-effect level.
OSHA PEL--Occupational Safety and Health Administration's permissible exposure limit expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.
RfC--Reference concentration.

^a Health numbers are toxicological numbers from animal testing or risk assessment values developed by EPA.
^b Regulatory numbers are values that have been incorporated in Government regulations, while advisory numbers are nonregulatory values provided by the Government or other groups as advice.
^c The LOAEL and NOAEL are from the critical study used as the basis for the EPA RfC.

References

1. U.S. Environmental Protection Agency. Updated Health Effects Assessment for Methyl Ethyl Ketone. EPA/600/8-89/093. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1990.
2. U.S. Environmental Protection Agency. Health Advisory for Methyl Ethyl Ketone. Office of Drinking Water, Washington, DC. 1987.
3. E.J. Calabrese and E.M. Kenyon. Air Toxics and Risk Assessment. Lewis Publishers, Chelsea, MI. 1991.
4. U.S. Department of Health and Human Services. Hazardous Substances Data Bank (HSDB, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.
5. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical Substances (RTECS, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.
6. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Methyl Ethyl Ketone. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1993.
7. U.S. Environmental Protection Agency. Technical Background Document to Support Rulemaking Pursuant to the Clean Air Act--Section 112(g). Ranking of Pollutants with Respect to Hazard to Human Health. EPA­450/3-92-010. Emissions Standards Division, Office of Air Quality Planning and Standards, Research Triangle Park, NC. 1994.
8. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.
9. U.S. Environmental Protection Agency. Assessment Tools for the Evaluation of Risk (ASTER, online database). Environmental Research Laboratory, Duluth, MN. 1993.