EPA 749-F-94-015a CHEMICAL SUMMARY FOR METHYL ETHYL KETONE prepared by OFFICE OF POLLUTION PREVENTION AND TOXICS U.S. ENVIRONMENTAL PROTECTION AGENCY September 1994 This summary is based on information retrieved from a systematic search limited to secondary sources (see Appendix A). These sources include online databases, unpublished EPA information, government publications, review documents, and standard reference materials. No attempt has been made to verify information in these databases and secondary sources. I. CHEMICAL IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES The chemical identity and physical/chemical properties of methyl ethyl ketone are summarized in Table 1. TABLE 1. CHEMICAL IDENTITY AND CHEMICAL/PHYSICAL PROPERTIES OF METHYL ETHYL KETONE _______________________________________________________________________ Characteristic/Property Data Reference _______________________________________________________________________ CAS No. 78-93-3 Common Synonyms 2-Butanone, MEK Verschueren 1983 Molecular Formula C4H80 Chemical Structure O || CH3-C-CH2-CH3 Physical State liquid Budavari 1989 Molecular Weight 72.10 Budavari 1989 Melting Point -86øC Budavari 1989 Boiling Point 79.6øC Budavari 1989 Water Solubility 353 g/L @ 10øC; 190 g/L @ 90øC Verschueren 1983 Specific gravity 0.805 @ 20/4øC Verschueren 1983 Vapor Density (air = 1) 2.41 Verschueren 1983 KOC 4.5 -50 (estimated) U.S. EPA 1989 Log KOW 0.29 (estimated) U.S. EPA 1989 Vapor Pressure 77.5 mm Hg @ 20øC Verschueren 1983 98.0 mm Hg @ 25øC U.S. EPA 1985 Reactivity Liquid and vapor are flammable. U.S. Air Force 1989 Flash Point -6øC (closed cup) Budavari 1989 Henry's Law Constant 4.16 to 6.11 X 10-5 atm-m3/mol @ 25øC (estimated) U.S. EPA 1985 Fish Bioconcentration Factor <1 (estimated) U.S. EPA 1985 Odor Threshold 5 to 10 ppm (in air) U.S. Air Force 1989 Conversion Factors 1 ppm = 2.94 mg/m3 1 mg/m3 = 0.34 ppm Verschueren 1983 _______________________________________________________________________ II. PRODUCTION, USE, AND TRENDS A. Production There are three methyl ethyl ketone producers in the United States. Table 2 lists producers, plant locations, and plant capacities. Annual US capacity is approximately 545 million pounds. In 1992, an estimated 494 million pounds of methyl ethyl ketone were produced in the US. During that same year, 55 million pounds were imported into the US and 112 million pounds were exported (Mannsville 1993). B. Use Methyl ethyl ketone is used in a number of industrial applications. The primary use of methyl ethyl ketone, accounting for approxi- mately 63 percent of all use, is as a solvent in protective coatings. It is also used as a solvent in adhesives; printing inks; paint removers; in the production of magnetic tapes; and in dewaxing lubricating oil. Methyl ethyl ketone is used as a chemical intermediate in several reactions, including condensation; halogenation; ammonolysis; and oxidation. Small amounts of methyl ethyl ketone are also used as a sterilizer for surgical instru- ments, hypodermic needles, syringes, and dental instruments; as an extraction solvent for hardwood pulping and vegetable oil; and as a solvent in pharmaceutical and cosmetic production (Mannsville 1993; HSDB 1994). Table 3 shows the estimated 1992 US end-use pattern for methyl ethyl ketone. C. Trends Demand for methyl ethyl ketone is expected to decrease gradually until alternative, low volatile organic carbon (VOC) coating technologies are readily available (Mannsville 1993). Once such alternatives are available, demand is expected to decrease more rapidly. TABLE 2. United States Producers of Methyl Ethyl Ketone _______________________________________________________________________ Company Plant Location Plant Capacity (in millions of pounds) _______________________________________________________________________ Exxon Chemical Baton Rouge, LA 230 Hoechst Celanese Pampa, TX 85 Shell Chemical Norco, LA 230 _______________________________________________________________________ Source: Mannsville 1993. TABLE 3. Estimated 1992 United States End-Use Pattern of Methyl Ethyl Keton _______________________________________________________________________ Use of Methyl Ethyl Ketone Percentage of US (typical Standard Industrial Methyl Ethyl Ketone Use Classification (SIC) Code) (see end note 1) _________________________________________________________________________ Protective coatings solvent (production, SIC 2851) 63% Adhesives solvent (production, SIC 2891) 13% Magnetic tapes (production, SIC 3652, 3695) 10% Lubricating oil dewaxing (production, SIC 2992) 5% Chemical intermediate (production, SIC 2865, 2869) 4% Printing inks (production, SIC 2893) 3% Miscellaneous (no applicable SIC Code(s)) 2% _______________________________________________________________________ Source: Mannsville 1993. III. ENVIRONMENTAL FATE A. Environmental Release Of the total methyl ethyl ketone released to the environment almost all eventually enters the air. Methyl ethyl ketone is released into the environment from industrial and domestic uses. The largest man made sources of methyl ethyl ketone release are from its primary use as a solvent for coatings, resins, and adhesives (U.S. EPA 1985). Methyl ethyl ketone has been found in cigarette smoke (500 ppm) and in gasoline engine exhaust (<0.1-1.0 ppm) (Verschueren 1983). Its use as a solvent in polyvinyl chloride pipe joint cement has introduced the chemical into drinking water (4.5 ppm, 6 months after installation) (HSDB 1994). It occurs naturally and has been found in a number of foods and beverages including swiss cheese (0.3 ppm), cream (0.154-0.177 ppm), barley, bread, honey, oranges, black tea, rum, non-alcoholic beverages (70 ppm), and ice cream (270 ppm) (HSDB 1994). In 1992, releases of methyl ethyl ketone to environmental media, as reported to the Toxic Chemical Release Inventory by certain types of US industries totaled about 91.3 million pounds. Of this amount, a total of 90.5 million pounds (99%) was released to the atmosphere, 153 thousand pounds were released to surface water, 365 thousand pounds to underground injection, and 242 thousand pounds were released to land (TRI92 1994). Although the atmospheric concentration of methyl ethyl ketone increases during episodes of severe photochemical smog (up to 14 ppb in Los Angeles, CA during a photochemical pollution episode), ambient concentrations are usually below the detection limit (0.01 ppb) in most urban areas. Air levels averaging 64 ppb have been measured near industrial sources of the chemical, and a concentration of 94 ppm has been measured in the vicinity of a chemical reclamation plant (HSDB 1994). Methyl ethyl ketone was detected in less than 5% of groundwater samples in a federal survey of drinking water supplies, and in only one (found at a level of 23 ppb) of 204 sites from 14 heavily industrialized river basins in the United States. The chemical has been detected in clouds, fog, and ice fog in California (trace-0.47 ppm in positive samples), but not detected in rain. It was found in rain in Japan. It was also detected in the trench leachate from two low-level radioactive disposal sites (HSDB 1994). B. Transport Methyl ethyl ketone is not expected to be retarded by adsorption to soils rich in organic material [estimated Koc = 4.5-50 (U.S. EPA 1989)]; therefore, it is expected to be mobile in soil and, subject to leaching from landfills. The relatively high vapor pressure [98.0 mm Hg @ 25øC (U.S. EPA 1985)] and estimated Henry's Law constant (4.16-6.11 x 10-5 atm m3/mol @ 25øC) indicate that it can volatilize from moist and dry soil (HSDB 1994). It does not adsorb significantly to suspended solids, and will volatilize to the atmosphere from surface waters (HSDB 1994; U.S. EPA 1985). C. Transformation/Persistence 1. Air - The main degradation pathway for methyl ethyl ketone in the atmosphere is reaction with photochemically produced hydroxyl radicals, primarily producing acetaldehyde. The half- life of methyl ethyl ketone from the reaction with hydroxyl radicals has been estimated to be about 2.3 days (HSDB 1994). Direct photolysis with a calculated half-life of about 15.4 hours at a solar zenith angle of 30ø is expected to occur (U.S. EPA 1985). Deposition by rain or fog may play a minor role in transporting methyl ethyl ketone from the atmosphere. It has also been shown to be reactive in smog chamber studies (U.S. EPA 1985). 2. Soil - In wet or dry soil, methyl ethyl ketone will volatilize to air and may undergo photolysis on the soil surface (U.S. EPA 1985). It is also highly mobile and may be leached from the soil by water, and has been shown to be degradated by cultures of soil bacteria (U.S. EPA 1985). 3. Water - The most important fate process for methyl ethyl ketone in water is volatilization (estimated half-times of 3 and 12 days, for rivers and lakes, respectively). Complete aerobic biodegradation of methyl ethyl ketone has been reported in about 5-10 days following inoculation with sewage or polluted surface water. Longer times were required for degradation in marine water. Anaerobic degradation occurred after an acclimation period of about one week (HSDB 1994). Direct photolysis near the surface is also thought to be a possible mechanism, but was not measured (HSDB 1994). It is not expected to undergo chemical hydrolysis or to be bound to sediment or suspended organic matter (HSDB 1994). 4. Biota - Methyl ethyl ketone is not expected to bioconcentrate in fish or aquatic organisms; its estimated fish bioconcentra- tion factor is less than 1 (U.S. EPA 1985). IV. HUMAN HEALTH EFFECTS A. Pharmacokinetics 1. Absorption - Studies in humans and animals have demonstrated that methyl ethyl ketone can be absorbed via the lungs, the skin, and the gastrointestinal system. The concentration of methyl ethyl ketone in the atmosphere has been correlated with the alveolar concentration (70% alveolar retention) and blood levels in humans (U.S. EPA 1985). Pulmonary absorption values range from 41.1% to 55.8% (WHO 1993). The relative uptake through the lungs by humans was about 53% through a 4 hour exposure at 200 ppm (HSDB 1994; WHO 1993). Oral studies in rats have demonstrated that the peak blood level of methyl ethyl ketone (0.95 mg/mL) was reached in 4 hours following oral administration of the chemical in water (1690 mg/kg) (U.S. EPA 1985). Methyl ethyl ketone can also be absorbed through intact human skin. A steady state concentration in expired air was reached in 2-3 hours following exposure of the palmar surface of the forearm of volunteers (Krasavage et al. 1982). Absorption is more rapid through moist skin than through dry skin, and the rate of percutaneous absorption has been estimated to range from 5 to 10 micrograms/cm2/min (WHO 1993). 2. Distribution - The relative solubility of methyl ethyl ketone in various human tissues and organs compared to blood (tissue/blood partition coefficient) was shown to be similar in the kidney, liver, brain, heart, and lung and in fat and muscle tissue. This indicates a potential for even and widespread distribution of methyl ethyl ketone in human tissues (U.S. EPA 1985). It has also been shown to cross the placenta and enter the human fetus (WHO 1993). 3. Metabolism - Experiments with guinea pigs and rats have shown that methyl ethyl ketone is metabolized by oxidative hydroxylation, forming 3-hydroxy-2-butanone, which is further reduced to 2,3-butanediol. Methyl ethyl ketone is also reversibly reduced to 2-butanol (U.S. EPA 1985). 4. Excretion - The half-life of methyl ethyl ketone in the blood of guinea pigs was reported to be 270 minutes, following intraperitoneal injection of 450 mg/kg. The clearance time was 12 hours (U.S. EPA 1985). It has been estimated that humans eliminate 30 to 40% of methyl ethyl ketone intake in expired air (HSDB 1994). The unchanged chemical and its metabolite, 3-hydroxy-2-butanone were measured in the urine of workers occupationally exposed to 8 to 272 mg/m3. The metabolite was only identified in workers exposed to the higher levels, and was correlated with the level of exposure and the urinary concentration of methyl ethyl ketone (U.S. EPA 1985). The plasma half-time in humans has be estimated at 49-96 minutes with an apparent clearance rate of 0.6 L/minute (ATSDR 1992). B. Acute Toxicity Acute exposure to moderate to high doses of methyl ethyl ketone can cause headaches, nausea, and irritation of the eyes and respiratory tract; high doses can also result in narcosis. Eye contact with liquid methyl ethyl ketone can cause corneal injury. 1. Humans - Volunteers complained of mild nose and throat irritation when exposed to 100 ppm. The irritation became objectionable when the concentration was raised to 300 ppm (ATSDR 1992). Workers occupationally exposure to an atmosphere containing 300 to 500 ppm (126 to 210 mg/kg/day) (see end note 2) complained of headaches, nausea, and respiratory tract irrita- tion. Momentary exposure to 33,000 or 100,000 ppm caused intolerable irritation of the eyes, nose and throat (Krasavage et al. 1982). Workers exposed either by inhalation (300-600 ppm) or by skin contact to methyl ethyl ketone developed numbness in the extremities and dermatitis. High concentrations can result in central nervous system depression (see Section IV.G.1.). Eye contact with liquid methyl ethyl ketone causes painful irritation, and can result in corneal injury (Krasavage et al. 1982; HSDB 1994). 2. Animals - Oral LD50 values of 2737 and 4050 mg/kg were reported for rats and mice, respectively. Inhalation LC50 values of 23,500 mg/m3/8 hours for rats and 40,000 mg/m3/2 hours for mice were reported (U.S. EPA 1985). Guinea pigs exposed to 10,000 ppm methyl ethyl ketone developed liver and kidney congestion, but no effects were seen at 3500 ppm (ATSDR 1992). C. Subchronic/Chronic Effects Human studies have indicated that extended or repeated exposure to relatively high concentrations of methyl ethyl ketone can result in adverse central nervous system effects. Animal studies indicate that extended or repeated inhalation exposure to relatively high concentrations of methyl ethyl ketone can result in hepatic and renal toxicity. 1. Humans - Dermatitis, gastrointestinal upset, loss of appetite and weight, and neurological problems (see Section IV.G.1.) were reported by individuals occupationally exposed to methyl ethyl ketone, apparently in the absence of other solvents (WHO 1993). Neurological problems were also reported by workers chronically exposed to 300-600 ppm of the chemical (WHO 1993). All other available studies describing subchronic/chronic occupational exposure involved a mixture of organic solvents that contained methyl ethyl ketone. A variety of nervous system effects were consistently described after prolonged exposure to these mixtures (see Section IV.G.1.) (WHO 1993). 2. Animals - Male and female Fischer 344 rats were exposed to 0, 1250, 2500, or 5000 ppm methyl ethyl ketone by inhalation 6 hours/day, 5 days/week, for 90 days. No treatment related differences in food consumption, in eye effects, in neurological functioning, or in histopathologies were reported (U.S. EPA 1985). Increased serum alanine amino transferase in females was the only effect at 2500 ppm; increased absolute and relative liver weight were seen in both sexes at 5000 ppm. Females also developed decreased relative brain weight, and increased blood levels of alkaline phosphatase, glucose, and potassium at 5000 ppm. The mean body weights of both sexes were decreased at 5000 ppm, but increased at the other dose levels compared to the controls. In another inhalation study Fischer 344 rats were exposed by inhalation to 5041 ppm (14,870 mg/m3), 2518 ppm, or 1254 ppm methyl ethyl ketone for 6 hours/ day, 5 days/week for 90 days. No significant effects on food consumption, eyes, or morphology were observed (WHO 1993). Increased absolute and relative liver weight, decreased body weight, increased relative kidney weight, decreased relative brain and spleen weights, and increased mean corpuscular hemoglobin were reported at the high dose. Increased body weights were reported at the low and intermediate dose. Male rats exposed to 10,000 ppm methyl ethyl ketone 8 hours/day, 7 days/week developed severe irritation in the upper respiratory tract within a few days and died during the 7th week of exposure of bronchopneumonia (ATSDR 1992). D. Carcinogenicity There is inadequate information to evaluate the carcinogenicity of methyl ethyl ketone in humans and in laboratory animals. 1. Humans - No excess cancer incidence was found in an epidemiological study of 446 male workers in two methyl ethyl ketone dewaxing plants. The deaths observed were below the expected, and overall deaths from cancer were also below the expected. An increase in tumors of the buccal cavity and pharynx was seen but the numbers were small (2 observed, 0.13 expected) and lung cancers were significantly decreased (1 observed, 6.02 expected) (ATSDR 1992; WHO 1993). The overall cancer-related mortality was less than expected in another epidemiological study of 1008 male oil refinery workers exposed to 1-4 ppm methyl ethyl ketone. There were no increases in buccal and pharyngeal cancers seen in this study (ATSDR 1992). 2. Animals - Methyl ethyl ketone was applied to the skin of mice twice weekly for one year (50 mg/dose). No tumors were reported (U.S. EPA 1989). No information on the carcinogenicity of methyl ethyl ketone by other routes of administration were found in the secondary sources searched. E. Genotoxicity Results from four out of the five short term mutagenicity assays, requested by and submitted to EPA under the Toxic Substances Control Act (TSCA), indicate methyl ethyl ketone is not mutagenic. Methyl ethyl ketone is negative in the Ames test (in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 with or without S-9 metabolic activation); the mouse lymphoma test; the cell transformation assay; and the mouse micronucleus test. Results from the Section 4 unscheduled DNA test was concluded to be positive (Cimino 1985). Most of the information from other secondary sources also indicate that methyl ethyl ketone is not genotoxic. Methyl ethyl ketone was negative in E. coli tester strains WP2 and WP2uvrA (WHO 1993). It was negative in the mitotic gene conversion assay in S. cerevisiae tester strain JD1 (WHO 1993). It was negative in the micronucleus test in both CD1 mice and Chinese hamsters (WHO 1993). It was a strong inducer of aneuploidy in S. cerevisiae strain D61.M (U.S. EPA 1989). F. Developmental/Reproductive Toxicity Animal studies indicate that exposure to high methyl ethyl ketone concentrations in air breathed during pregnancy can cause fetal toxicity and possibly adverse developmental effects. EPA has derived an oral reference dose (RfD) (see end note 3) of 0.6 mg/kg/day, based on developmental effects of a metabolite (2-butanol) of MEK. EPA has derived an inhalation reference concentration (RfC) (see end note 4) of 1 mg/m3 for methyl ethyl ketone, based on its developmental effects. 1. Humans - No information on the developmental/reproductive toxicity of methyl ethyl ketone was found in the secondary sources searched. 2. Animals - Since there are no appropriate oral studies on methyl ethyl ketone, the U.S. EPA (1994) calculated a chronic oral RfD for methyl ethyl ketone of 0.6 mg/kg/day, based on decreased birth weights seen in a multigeneration study with its metabolic intermediate, 2-butanol. Male and female Wistar rats (30/sex/ group) were given 2-butanol in drinking water at 0, 0.3, 1.0, or 3.0% nine weeks before mating through gestation and lactation. The high dose was reduced to 2.0% for the second generation. Decreased fetal weight and decreased pup survivability were reported for the first generation at 3.0% 2-butanol. Decreased fetal weight was seen in the second generation at 2.0%. Increases in the incidences of missing sternebrae, wavy ribs, and incomplete vertebrae ossification at 2%, compared to the 1.0 and 0.3% groups, were seen. However, because of high incidences of these develop- mental effects in the control group, they could not be determined to be treatment related. The 1.0% dose, equivalent to 1771 mg/kg/ day, was identified as a no-adverse-effect-level (NOAEL), and the 2.0% dose was identified as a lowest-adverse-effect-level (LOAEL) (U.S. EPA 1994). The U.S. EPA (1994) calculated a chronic inhalation reference concentration (RfC) of 1.0 mg/m3 for methyl ethyl ketone, based on decreased fetal birth weight seen in a mouse inhalation study. Pregnant mice were exposed by inhalation to atmospheric concentrations of 0, 398, 1010, or 3020 ppm methyl ethyl ketone 7 hours/day during days 6-15 of gestation. Decreased fetal body weight was seen at 3020 ppm. There was an increased incidence of fetuses and litters with malformations in the treated groups, but the increases were not statistically significant. A NOAEL of 1010 ppm and a LOAEL of 3020 ppm were identified (U.S. EPA 1994). Groups of 25 pregnant Sprague-Dawley rats were exposed to air concentrations of 400, 1000, or 3000 ppm methyl ethyl ketone 7 hours/day during days 6-15 of gestation. The control group contained 35 rats. Maternal body weight gain was decreased and water consumption was increased in dams receiving 3000 ppm. There were no treatment related effects on the pregnancy rate, the number of implantations per litter, or the percent live fetuses. A total of five fetuses with at least one external or soft tissue malformation were reported, but were distributed in all groups including the control. Increased incidences of delayed ossification and extra ribs at the 3000 ppm dose were attributed to fetal toxicity (U.S. EPA 1989). G. Neurotoxicity Neurological effects, observed in humans and animals exposed to high concentrations of methyl ethyl ketone, appear to be reversible. Concentrations high enough to cause central nervous system depression also cause severe pulmonary irritation. 1. Humans - American workers exposed to 300-600 ppm methyl ethyl ketone reported numbness in the fingers and toes. Italian workers chronically exposed to the chemical developed reduced nerve conduction velocities, headaches, dizziness, and muscle hypotrophy (WHO 1993). Most reports involving human exposure to methyl ethyl ketone describe effects seen after exposure to mixtures of solvents. Methyl ethyl ketone has been shown to potentiate the effects of other solvents, especially n-hexane (U.S. EPA 1989). Workers exposed to a mixture containing methyl ethyl ketone (39 ppm), n-hexane (90 ppm), cyclohexane (92 ppm), and ethyl acetate (57 ppm) complained of sleepiness, dizziness weakness, paraesthesia, and hypo-aesthesia (WHO 1993). Reductions in the maximal motor and distal sensory nerve conduction velocities in the median and ulnar nerves and decreased maximal motor nerve conduction velocity in the peroneal nerve were reported after 2-8 years exposure to a mixture containing methyl ethyl ketone (60 ppm), n-hexane (196 ppm), cyclohexane (170 ppm) and ethyl acetate (100 ppm). The latency of sensory peak action potentials were increased and the amplitude of peripheral nerve action potentials were decreased. The effects were attributed to n-hexane, possibly potentiated by methyl ethyl ketone (WHO 1993). 2. Animals - Wistar rats exposed to 200 ppm (roughly equivalent to 244 mg/kg/dy) methyl ethyl ketone 12 hours/day, 7 days/week, for 24 weeks exhibited transient increases in motor nerve conduction velocities and decreased distal motor latency. These effects were observed after four weeks of exposure but not after 12 weeks (U.S. EPA 1989). Transient behavioral changes were reported in baboons exposed to 100 ppm for 7 days. Intravenous infusion of 5 mg/kg methyl ethyl ketone per hour into Sprague- Dawley rats resulted in depression of the vestibulo-oculomotor reflex. Depression of the central nervous system followed with continued infusion (WHO 1993). No neuropathology or histological changes were found in several experiments in chickens, cats, rats, and mice exposed to atmospheres containing up to 1500 ppm for up to 12 weeks. Exposure to high concentrations results in narcosis. Guinea pigs exposed to an atmospheric concentration of 10,000 ppm experience narcosis in four to five hours; however, irritation of the eyes and nose develops within four minutes (Krasavage et al. 1982). V. ENVIRONMENTAL EFFECTS The toxicity of methyl ethyl ketone in aquatic organisms is low; toxicity values are greater than 100 mg/L. It also has low toxicity in terrestrial rodents for inhalation exposure. A. Toxicity to Aquatic Organisms 24 Hour LC50 values for fish are: >5000 mg/L for Carassius auratus (goldfish); >400 mg/L for Cyprinodon variegatus (sheepshead minnow); and 5640 mg/L for Lepomis macrochirus (bluegill) (AQUIRE 1994). 96 Hours LC50 values for fish include: 3200 mg/L for Pimephales promelas (fathead minnow); 5600 mg/L for Gambusia affinis (mosquito fish); and 4467 mg/L for Lepomis macrochirus (bluegill) (WHO 1993). 24 Hour LC50 values of 8890 mg/L for Daphnia magna (water flea) and 1950 mg/L for Artemia salina (brine shrimp) were reported (WHO 1993). B. Toxicity to Terrestrial Organisms The toxicity information reported for rats and rabbits (see sections IV.B.2. and IV.C.2.) suggests that no adverse effects would be seen at expected environmental concentrations. C. Abiotic Effects Methyl ethyl ketone is known to contribute to photochemical smog episodes (Federal Register 1992). Smog chamber studies indicate that methyl ethyl ketone is of intermediate reactivity with degradation rates ranging from 1.5% in one hour to 33% in 6.5 hour (HSDB 1994). VI. EPA/OTHER FEDERAL ACTIVITY Voluntary reduction of methyl ethyl ketone environmental releases has occurred since 1991, as a result of a joint industry/EPA pollution prevention initiative known as the 33/50 program. The 1990 Clean Air Act Amendments list methyl ethyl ketone as a hazardous air pollutant. Occupational exposure to methyl ethyl ketone is regulated by the Occupational Safety and Health Administration (OSHA). The permissible exposure limit (PEL) is 200 parts per million parts of air (ppm) as an 8-hour time-weighted average (TWA) (29 CFR 1910.1000) (Mannsville 1993). Federal agencies/other groups that can provide additional information on methyl ethyl ketone are listed in Table 4 and 5. TABLE 4. EPA OFFICES AND CONTACT NUMBERS FOR INFORMATION ON METHYL ETHYL KETONE ________________________________________________________________________ EPA OFFICE LAW PHONE NUMBER ________________________________________________________________________ Pollution Prevention Toxic Substances Control Act & Toxics (Sec. 4/8A/8D) (202) 554-1404 Emergency Planning and Community Right-to-Know Act (EPCRA) Regulations (Sec. 313) (800) 424-9346 Toxics Release Inventory data (202) 260-1531 Air Clean Air Act (919) 541-0888 Solid Waste & Comprehensive Environmental Emergency Response Response, Compensation, and Liability Act (Superfund)/ Resource Conservation and Recovery Act / EPCRA (Sec. 304/311/312) (800) 424-9346 Water Safe Drinking Water Act (800) 426-4791 ________________________________________________________________________ TABLE 5. OTHER FEDERAL OFFICE/OTHER GROUP CONTACT NUMBERS FOR INFORMATION ON METHYL ETHYL KETONE __________________________________________________________________________ Other Agency/Department/Other Group Contact Number ___________________________________________________________________________ Agency for Toxic Substances & Disease Registry (404) 639-6000 American Conference of Governmental Industrial Hygienists Recommended TLV-TWA: 200 ppm; TLV-STEL 300 ppm (see end note 7) (ACGIH 1991) (513) 742-2020 Consumer Product Safety Commission (301) 504-0994 Food & Drug Administration (301) 443-3170 National Institute for Occupational Safety & Health Recommended TWA: 200 ppm; STEL 300 ppm; IDLH, 3000 ppm (see end note 5) (NIOSH 1992) (800) 356-4674 Occupational Safety & Health Administration Check local phone Permissible TWA: 200 ppm book for phone (see end note 6) (OSHA 1993) number under Department of Labor ___________________________________________________________________________ VII. END NOTES 1. Standard Industrial Classification code is the statistical classifica- tion standard for all Federal economic statistics. The code provides a convenient way to reference economic data on industries of interest to the researcher. SIC codes presented here are not intended to be an exhaustive listing; rather, the codes listed should provide an indication of where a chemical may be most likely to be found in commerce. 2. Calculated using the factor, 2.94 (Verschueren 1983), to convert ppm to mg/m3, which is multiplied by 0.1429 (the occupational 8-hour breathing rate, 10 m3, divided by the assumed adult body weight, 70 kg) to obtain the dose in mg/kg/day assuming 100% absorption (U.S. EPA 1988). 3. The RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of the daily exposure level for the human population, including sensitive subpopulations, that is likely to be without an appreciable risk of deleterious effects during the time period of concern. 4. An inhalation reference concentration is an estimate (with uncertainty spanning perhaps an order of magnitude) of the exposure level for the human population, including sensitive populations, that is likely to be without an appreciable risk of deleterious effects during the time period of concern. 5. TWA, occupational, Time Weighted Average; STEL, occupational, Short Term Exposure Limit, 15 min.; IDLH, Immediate Danger to Life and Health. 6. PEL-TWA, Permissible Exposure Limit-Time Weighted Average 7. TLV-TWA, Threshold Limit Value-Time Weighted Average; TLV-STEL, Threshold Limit Value-Short Term Exposure Limit VIII. CITED REFERENCES ACGIH. 1991. Documentation of the Threshold Limit Values and Biological Exposure Indices, Sixth edition. American Conference of Governmental Industrial Hygienists, Inc., Cincinnati, OH. AQUIRE. 1994. Aquatic Information Retrieval online data base. Chemical Information Systems, Inc., a subsidiary of Fein-Marquart Assoc. Retrieved Aug, 1994. ATSDR. 1992. Agency for Toxic Substances and Disease Registry. Toxicological Profile for 2-Butanone. U.S. Department of Health and Human Services, Public Health Service. Atlanta, GA. Budavari S, O'Neil MJ, Smith A, Heckelman PE (Eds.). 1989. The Merck Index, 11th ed. Merck & Co., Inc., Rahway, N.J., p. 820. Cimino. 1985. Review of Mutagenicity Test Data on MIBK and MEK. Memorandum from M. Cimino (Toxic Effects Branch) to J. Kariya (Chemical Review and Evaluation Branch), Office of Toxic Substances, Washington, D.C. January 23, 1985. Federal Register. 1992. Part 51 - Requirements for Preparation, Adoption, and Submittal of Implementation Plans. Fed. Reg. 57:3945. HSDB. 1994. Hazardous Substances Data Bank. MEDLARS Online Information Retrieval system, National Library of Medicine. Retrieved 8/3/94. Krasavage, W.J., J.L. O'Donoghue and G.D. Divincenzo. 1982. Ketones. in: Clayton GD, Clayton FE. 1981-1982. Patty's Industrial Hygiene and Toxicology, 3rd ed., Vol. 2C. John Wiley & Sons, New York, pp. 4747-4751. Mannsville, 1993. Chemical Products Synopsis, Methyl Ethyl Ketone. Mannsville Chemical Products Corporation, 1993. NIOSH (National Institute for Occupational Safety and Health). 1992. NIOSH Recommendations for Occupational Safety and Health, Compendium of Policy Documents and Statements. Cincinnati OH. U.S. Department of Commerce, National Technical Information Service, PB92-162536, Table 1. OSHA. 1993. Occupational Safety and Health Administration. Air Contaminants Rule, Table Z-1, Limits for Air Contaminants. 29 CFR part 1910, Part V, p. 35345. TRI92. 1994. 1992 Toxics Release Inventory, Public Data Release. U.S. EPA, Office of Pollution Prevention and Toxics (7408). U.S. Air Force. 1989. Methyl Ethyl Ketone. in: The Installation Restoration Toxicology Guide, Vols. 1-5. Wright-Patterson Air Force Base, OH. pp: 41-1 - 41-31. U.S. EPA. 1985. Health and Environmental Effects Profile for Methyl Ethyl Ketone. U.S. Environmental Protection Agency, Office of Solid Waste and Emergency Response, Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH. ECAO-CIN-P143. U.S. EPA. 1988. U.S. Environmental Protection Agency. Methodology for Evaluating Potential Carcinogenicity in Support of Reportable Quantity Adjustments Pursuant to CERCLA Section 102. Carcinogen Assessment Group, Office of Health and Environmental Assessment, U.S. EPA, Washington, D.C., pp. 21, 22. OHEA-C-073. U.S. EPA. 1989. Updated Health Effects Assessment for Methyl Ethyl Ketone. U.S. Environmental Protection Agency, Office of Solid Waste and Emergency Response, Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH. ECAO-CIN-H003a. U.S. EPA. 1994. Integrated Risk Information System (IRIS) Online. Coversheet for Methyl ethyl ketone. Office of Health and Environmental Assessment, U.S. EPA, Cincinnati, OH. Retrieved 8/94. Verschueren, K. 1983. Methyl ethyl ketone. in: Handbook of Environmental Data on Organic Chemicals, Second Edition. Van Nostrand Reinhold Co., New York, pp: 850-852. WHO (World Health Organization). 1993. Environmental Health Criteria 143, Methyl Ethyl Ketone. First draft prepared by R.B. Williams, U.S. EPA. Sponsored by the United Nations Environment Programme, the International Labour Organization, and the World Health Organization. WHO, Geneva. APPENDIX A. SOURCES SEARCHED FOR FACT SHEET PREPARATION ACGIH. 1991. Documentation of the Threshold Limit Values and Biological Exposure Indices, Sixth edition. American Conference of Governmental Industrial Hygienists, Inc., Cincinnati, OH. AQUIRE. 1994. IPA ERL-Duluth's Aquatic Ecotoxicology Data Systems. U.S. EPA, Duluth, MN. ATSDR. 1989-1994. Agency for Toxic Substances and Disease Registry. Toxicological Profiles. Chamblee, GA: ATSDR. BIODEG. 1994. Syracuse Research Corporation's Environmental Fate Data Bases. Syracuse Research Corporation, Syracuse, NY. Budavari S, O'Neil MJ, Smith A, Heckelman PE (Eds.). 1989. The Merck Index, 11th ed. Rahway, N.J.: Merck & Co., Inc. CHEMFATE. 1994. Syracuse Research Corporation's Environmental Fate Data Bases. Syracuse Research Corporation, Syracuse, NY. Clayton GD, Clayton FE. 1981-1982. Patty's Industrial Hygiene and Toxicology, 3rd ed., Vol. 2C. New York: John Wiley & Sons. GENETOX. 1994. U.S. EPA GENETOX Program, computerized database. HSDB. 1994. Hazardous Substances Data Bank. MEDLARS Online Information Retrieval System, National Library of Medicine. IARC. 1979-1994. International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. Lyon: IARC. NIOSH (National Institute for Occupational Safety and Health). 1992. NIOSH Recommendations for Occupational Safety and Health. Compendium of Policy Documents and Statements. Cincinnati, OH: NIOSH. NTP. 1994. National Toxicology Program. Toxicology and Carcinogenesis Studies. Tech Rep Ser. NTP. 1994. National Toxicology Program. Management Status Report. Produced from NTP Chemtrack system. April 8, 1994. National Toxicology Program, Research Triangle Park, NC. OSHA. 1994. Occupational Safety and Health Administration. Table Z-2. Limits for Air Contaminants. RTECS. 1994. Registry of Toxic Effects of Chemical Substances. MEDLARS Online Information Retrieval System, National Library of Medicine. TRI92. 1994. 1992 Toxics Release Inventory, Public Data Release. U.S. EPA, Office of Pollution Prevention and Toxics (7408). U.S. Air Force. 1989. The Installation Restoration Toxicology Guide, Vols. 1-5. Wright-Patterson Air Force Base, OH. U.S. EPA (U.S. Environmental Protection Agency). 1991. Table 302.4 List of Hazardous Substances and Reportable Quantities 40 CFR, part 302.4:3-271. U.S. EPA. Most current. Drinking Water Regulations and Health Advisories. Office of Drinking Water, U.S. Environmental Protection Agency, Washington, D.C. U.S. EPA. Most Current. Health Effects Assessment Summary Tables. Cincinnati, OH: Environmental Criteria and Assessment Office, U.S.EPA. U.S. EPA reviews such as Health and Environmental Effects Documents, Health and Environmental Effect Profiles, and Health and Environmental Assessments. U.S. EPA. 1994. Integrated Risk Information System (IRIS) Online. Cincinnati, OH: Office of Health and Environmental Assessment.