Methyl Isobutyl Ketone

Hazardous Air Pollutants (HAPs)

Flammable agents - 3rd degree

Volatile Organic Compound (VOC)

Cosmetics ingredient -> Fragrance; Solvent

Cosmetic ingredients (MIBK) -> CIR (Cosmetic Ingredient Review)

Solvent; Denaturant

log Kow = 1.31

1.31

1.38

Pleasant odor

Faint, ketonic and camphor odor

Fruity, ethereal odor

0.802 at 68 °F (USCG, 1999) - Less dense than water; will float

0.7965 g/cu cm at 25 °C

Density: 0.8042 at 20 °C/20 °C

Bulk density: 6.68 lb/gal at 20 °C

Relative density (water = 1): 0.80

0.796-0.799

Liquid

Colorless liquid

Danger

H225: Highly Flammable liquid and vapor [Danger Flammable liquids]

P203, P210, P233, P240, P241, P242, P243, P261, P264+P265, P271, P280, P303+P361+P353, P304+P340, P305+P351+P338, P317, P318, P319, P337+P317, P370+P378, P403+P233, P403+P235, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for < 0.1% (2 of 4455) of reports.

Danger

H225 (> 99.9%): Highly Flammable liquid and vapor [Danger Flammable liquids]

Chemical: 2-Pentanone, 4-methyl-

Hazard Traits - Carcinogenicity; Developmental Toxicity; Hepatotoxicity and Digestive System Toxicity; Nephrotoxicity and Other Toxicity to the Urinary System; Neurotoxicity; Ocular Toxicity

List II Chemical: A chemical, other than a List I chemical, specified by regulation that, in addition to legitimate uses, is used in manufacturing a controlled substance in violation of the Act. (21 eCFR 1310.02)

Regulation (EC) No 178/2002 (amended)

2-Pentanone, 4-methyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 2-Pentanone, 4-methyl- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 18-01-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/14866

Special Hazards of Combustion Products: Irritating vapors are generated when heated.

· HIGHLY FLAMMABLE: Will be easily ignited by heat, sparks or flames.

Highly flammable. Vapour/air mixtures are explosive.

Vapor causes irritation of eyes and nose; high concentrations cause anesthesia and depression. Liquid dries out skin and may cause dermatitis; irritates eyes but does not injure them. (USCG, 1999)

· Inhalation or contact with material may irritate or burn skin and eyes.

Methyl isobutyl ketone is used as a solvent for gums, resins, paints, varnishes, lacquers, and nitrocellulose. Acute (short-term) exposure to methyl isobutyl ketone may irritate the eyes and mucous membranes, and cause weakness, headache, nausea, lightheadedness, vomiting, dizziness, incoordination, narcosis in humans. Chronic (long-term) occupational exposure to methyl isobutyl ketone has been observed to cause nausea, headache, burning in the eyes, weakness, insomnia, intestinal pain, and slight enlargement of the liver in humans. Lethargy and kidney and liver effects have been observed in rats and mice chronically exposed by gavage (experimentally placing the chemical in the stomach), ingestion, and inhalation. EPA has classified methyl isobutyl ketone as a Group D, not classifiable as to human carcinogenicity.

MIBK is in the list of Some volatile substances which may be abused by inhalation published on the web site of the U.N. International Drug Control Programme, indicating its potential to cause narcosis in workers. [Reference #1] Fatty livers are observed in guinea pigs exposed to lethal concentrations (28,000 ppm). [HSDB] TLV basis is eye and respiratory tract irritation and kidney damage. [ACGIH]

1245 127

1245 127

Methyl isobutyl ketone is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and 2) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.

Methyl isobutyl ketone is an indirect food additive for use only as a component of adhesives.

Excerpt from ERG Guide 127 [Flammable Liquids (Water-Miscible)]:

Use powder, AFFF, foam, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water.

Fresh air, rest. Refer for medical attention.

Remove contaminated clothes. Rinse skin with plenty of water or shower. Refer for medical attention .

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Do NOT induce vomiting. Refer for medical attention .

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.

· ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

General First Aid:

(General first aid procedures)

Hazardous decomposition products formed under fire conditions: Carbon oxides, Oxides of phosphorus.

Vapors are heavier than air and may travel to a source of ignition and flash back

· Wear positive pressure self-contained breathing apparatus (SCBA).

Biological Exposure Indices (BEI) [ACGIH] - MIBK in urine = 1 mg/L; sample at end of shift; [ACGIH]

20.0 [ppm]

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

Fire extinguishers containing carbon dioxide, dry powder, or foam are recommended. Flashback along a vapor 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.

If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may be ineffective. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use "alcohol" foam, dry chemical or carbon dioxide.

Use water spray, dry chemical, "alcohol resistance" foam, or carbon dioxide. Water may be ineffective. Ue water spray to keep fire-exposed containers cool.

Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Store at Room Temperature.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

Drums should be stored in a well-ventilated area away from sources of ignition and heat. The storage temperature should not exceed 40 °C.

Store in a cool, dry, well-ventilated location. Outside or detached storage is preferred. Store away from oxidizers and reducing agents.

Conditions that could lead to autoxidation (presence of air, light, heat, or heavy metals) or condensation (strongly acidic or basic media) should be avoided during storage. Containers of V2A steel are recommended for both storage and transportation.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

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.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U161 and F003, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

Product: Product: Burn in a chemical incinerator equipped with an afterburner and scrubber but exert extra care in igniting as this material is highly flammable. Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Contaminated packaging: Dispose of as unused product.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

A good candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids. A good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A good candidate for liquid injection incineration at a temperature range of 650 to 1,600 °C and a residence time of 0.1 to 2 seconds.

For more Disposal Methods (Complete) data for Methyl isobutyl ketone (9 total), please visit the HSDB record page.

Methyl isobutyl ketone has been identified in the expired air from a non-smoking heterogenous study population(1). Methyl isobutyl ketone was found in expelled breath of humans at 1-10 ppb(2). Methyl isobutyl ketone had air concentration/urinary concentration correlation coefficients of 0.81 and 0.91 in 36 and 28 human subjects, respectively(3).

Methyl isobutyl ketone (MIBK) has recently been shown to potentiate the cholestasis induced by manganese-bilirubin (Mn-BR) or manganese (Mn) in rats. In this study, we investigated the effect of 4-methyl-2-pentanol (4MPOL) and 4-hydroxymethyl isobutyl ketone (4-OHMIBK), two major metabolites of MIBK, on these models of cholestasis. Dosages varying from 1.88 to 15 mmol/kg 4MPOL or 4-OHMIBK were administered once, 18 hr prior to the administration of a cholestatic Mn-BR combination. The cholestatic effect of the manganese-bilirubin combination was enhanced with dosages of 4MPOL of 3.75 mmol/kg and larger. On the other hand, dosages smaller than 15 mmol/kg of 4-OHMIBK did not potentiate the Mn-BR cholestasis. Daily pretreatment for 3 days resulted in an increased response to the cholestatic challenges of either Mn-BR or Mn alone. 4MPOL administered repetitively was a better potentiator than 4-OHMIBK with the Mn-BR model of cholestasis. However, with Mn alone, 4-OHMIBK proved to be more effective. 4MPOL and 4-OHMIBK per se were devoid of cholestatic properties, since the bile flow measured prior to the cholestatic challenge was not decreased and in some cases was significantly greater than that of vehicle-pretreated animals. These results show that MIBK metabolites can potentiate the cholestatic form of hepatotoxicity. /4-methyl-2-pentanol and 4-hydroxymethyl isobutyl ketone (metabolites)/

MnBK and MiBK prolong the duration of ketamine-, pentobarbital-, thiopental- and ethanol-induced loss of righting reflex (LRR) in mice. In equimolar doses, (5 mmol/kg ip), both isomers were equipotent with respect to the enhancement of ketamine-, pentobarbital-, and thiopental-induced LRR. However, MnBK was significantly more effective (twice as effective) than its isomer with respect to enhancing ethanol-induced LRR. An attempt to explain the difference in effectiveness between the two isomers was carried out. The effects of both ketones and their principal metabolites, (2-hexanol (2-HOL), 2,5-hexanedione (2,5-HD), 4-methyl-2-pentanol (4-MPOL) and 4-hydroxy 4-methyl-2-pentanone (HMP)) on ethanol-induced LRR and ethanol elimination were studied in mice. The ketones and their metabolites were dissolved in corn oil and injected intraperitoneally 30 min before 4 g/kg ethanol for LRR and 2 g/kg for ethanol elimination. Ethanol-induced LRR was significantly prolonged by the following dosages (mmol/kg), MnBK, 5; MiBK, 5; 2-HOL, 2.5; 4-MPOL, 2.5; and HMP, 2.5; 2,5-HD, 2.5, however exerted no effect. Concentrations of ethanol in blood or brain upon return of the righting reflex were similar in solvent-treated and control animals. The mean elimination rate of ethanol was slower in groups pretreated with MnBK or 2-HOL as compared to control animals. Ethanol elimination in animals pretreated with MiBK, HMP, 4-MPOL, or 2,5-HD was similar to that in control animals. These ketones are known to have some central depressant action on their own. This by itself could lead to prolongation of ethanol-induced LRR. However, MnBK, as well as one of its principal metabolites, (2-HOL), markedly reduced ethanol elimination. This could explain the observation that MnBK has a greater potentiating effect on ethanol-induced LRR that its isomer, MiBK, which does not affect ethanol elimination.

An experiment /was conducted/ to investigate the mechanism of methyl isobutyl ketone synergism of n-hexane neurotoxicity ... The results suggest that the synergistic action of methyl isobutyl ketone on n-hexane neurotoxicity may be related to its ability to induce liver microsomal cytochrome p450, resulting in increased metabolic activation of n-hexane to more potent neurotoxic metabolites.

The potentiating properties of methyl isobutyl ketone (MIBK) ... on the acute cholestatic response induced by taurolithocholate (TLC) were investigated in male Sprague Dawley rats. Animals were pretreated with 3.75 to 15.0 nmol ... by gavage administration daily for 3 or 7 days. Intravenous injections of taurolithocholate were 5, 10, 15, 20, or 25 mg/kg. Bile was collected over 15 or 30 minute periods to measure bile flow. Daily ketone pretreatment resulted in an enhancement of the diminution in bile flow observed after taurolithocholate challenge. When the ... /ketone was/ administered without taurolithocholate challenge, cholestasis was not observed. Slight increases in bile flow did occur.

For more Interactions (Complete) data for Methyl isobutyl ketone (9 total), please visit the HSDB record page.

Developmental

Eyes, skin, respiratory system, central nervous system, liver, kidneys

EC50; Species: Selenastrum capricornutum (/Green/ algae); Concentration: 400 mg/ for 96 hr; Effect: growth rate

LD50; Species: Angelaius phoeniceus (Redwinged blackbird) oral 100 mg/kg

LC50; Species: Carassius auratus (Goldfish); Conditions: static; Concentration: 450 mg/L for 24 hr

LC50; Species: Pimephales promelas (fathead minnow) weight 0.12 g; Conditions: flow through bioassay, water hardness 45.5 mg/L CaCO3, temp: 25 +/- 1 °C, pH 7.5, dissolved oxygen greater than 60% of saturation; Concentration: 505 mg/L for 96 hr

For more Ecotoxicity Values (Complete) data for Methyl isobutyl ketone (19 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 70(SRC), determined from a log Kow of 1.31(2) and a regression-derived equation(3), indicates that methyl isobutyl ketone is expected to have high mobility in soil(SRC). Volatilization of methyl isobutyl ketone from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.4X10-4 atm-cu m/mole(SRC) derived from its vapor pressure, 19.9 mm Hg(4), and water solubility, 19,000 mg/L(5). Methyl isobutyl ketone is expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). An 84% of theoretical BOD using activated sludge in the Japanese MITI test(6) suggests that biodegradation is an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 70(SRC), determined from a log Kow of 1.31(2) and a regression-derived equation(3), indicates that methyl isobutyl ketone is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 1.4X10-4 atm-cu m/mole(SRC), derived from its vapor pressure, 19.9 mm Hg(4), and water solubility, 19,000 mg/L(5). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 9 hours and 6 days, respectively(SRC). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). An 84% of theoretical BOD using activated sludge in the Japanese MITI test(8) suggests that biodegradation is an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), methyl isobutyl ketone, which has a vapor pressure of 19.9 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase methyl isobutyl ketone is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 30(SRC), calculated from its rate constant of 1.3X10-11 cu cm/molecule-sec at 25 °C(3). Methyl isobutyl ketone absorbs UV at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Methyl isobutyl ketone was identified, not quantified, in the volatile component of baked potatoes(1). Methyl isobutyl ketone was detected in the volatiles of scrambled eggs (3 ng/g)(2), cured beef (0.03 mg/kg)(3) and cured chicken (0.06 mg/kg)(3).

Methyl isobutyl ketone has been reported found in orange and lemon juice, grape; vinegar, baked potato, papaya, ginger, wheat bread, cheeses, cooked egg, roast chicken, cooked beef, lamb fat, pork liver, hop oil, beer, cognac, coffee, tea, plumcot, plum brandy, mushroom, trassi, sesame seed, buck wheat, wort, elder, Bourbon vanilla, clary and red sage

The substance can be absorbed into the body by inhalation of its vapour and by ingestion.

inhalation, ingestion, skin and/or eye contact

Methyl isobutyl ketone was reported as 131.9, 0.01, and 0.01 ng/ml average in whole, 2%, and 1% milk, respectively, from 35 samples taken from 8 plants, located in AZ, CA, NV, and UT sampled Jan - Feb 2002(1).

Methyl isobutyl ketone has been reported found in milk

Based on the available animal and clinical data in this report, the CIR Expert Panel concludes that MIBK is safe as used in nail polish removers and as an alcohol denaturant in cosmetic products.

Safe for use in cosmetics, with qualifications

IDENTIFICATION AND USE: Methyl isobutyl ketone (MIBK) is a colorless liquid. It is used as a solvent for gums, resins, nitrocellulose, paints, varnishes, and lacquers. It is also used as denaturant for rubbing alcohol, in the manufacture of methyl amyl alcohol, and in dry-cleaning preparations. It is also widely used in rubber chemicals for the production of tyres. HUMAN STUDIES: Symptoms and signs of poisoning include: irritation of the eyes, skin, and respiratory tract, as well as CNS depression. Gastrointestinal pain and hepatic toxicity may occur with exposure to high concentrations. In workers exposed to up to 2050 mg MIBK/cu m (500 ppm) for 20-30 min per day and to 328 mg/cu m (80 ppm) for much of the remainder of the working day, over half of the 19 workers complained of weakness, loss of appetite, headache, eye irritation, stomach ache, nausea, vomiting, and sore throat. A few of the workers experienced insomnia, somnolence, heartburn, intestinal pain, and some unsteadiness. Four workers had slightly enlarged livers and six had a nonspecific colitis. Prolonged or repeated skin contact may cause drying and flaking of the skin. Accidental aspiration of liquid MIBK can cause chemical pneumonitis. ANIMAL STUDIES: MIBK elicited no dermal irritation to intact rabbit skin. Guinea pigs were exposed to 1000, 16,800, 28,000 ppm MIBK. The 1000 ppm level caused little or no irritation of eyes and nose of the animals. Guinea pigs showed a decreased respiratory rate during the first 6 hr of exposure attributed to a low grade CNS depression. The 16,800 ppm level caused immediate signs of eye and nose irritation followed by salivation, lacrimation, ataxia, and death. Nine of 10 animals died within 6 hr of exposure. The highest concentration used (28,000 ppm) killed 50 percent of the animals within 45 min. Only a few guinea pigs survived 60 min of exposure. Fatty livers and congestion of the brain, lungs and spleen were noted. Rats exposed to 25 ppm MIBK showed a minimal statistical increase in pressor lever response, but the discriminatory behavior of baboons was not impaired by exposures of 20-40 ppm. In rats exposed dermally to 300-600 mg MIBK/kg per day for 4 months, dose- and time-dependent morphological changes were observed in the skin, brain, liver, adrenals, spleen, and testis. Body temperature decreased and oxygen consumption increased. Reproductive toxicity of MIBK was evaluated in a two-generation inhalation study in rats. The only effect reported in offspring was significantly depressed body weights on day 14 postpartum in F1 and F2 male and female pups in mid- and high-exposure groups; however, pup body weights were not different from those of controls on days 7 and 21 post-partum. No other exposure-related changes were observed in any reproductive or developmental endpoint in either generation, including an absence of anatomical changes in F0 and parental F1 reproductive organs. Genotoxicity assays of MIBK included the Salmonella/microsome (Ames) assay, L5178Y/TK+/- mouse lymphoma assay, BALB/3T3 cell transformation assay, unscheduled DNA synthesis assay, and micronucleus assay. The presence of a marginal response only at the highest cytotoxic concentration tested in the L5178Y/TK+/- mouse lymphoma assay, the lack of reproducibility in the BALB/3T3 cell transformation assay, and clearly negative results in the Ames assay, unscheduled DNA synthesis and micronucleus assays, suggest that MIBK is unlikely to be genotoxic in mammalian systems. ECOTOXICITY STUDIES: Aquatic invertebrates are less sensitive than fish to the toxicity of MIBK. The toxicity of MIBK was also measured in the green alga Scenedesmus quadricauda, in which the 8-day threshold for toxicity was 725 mg/L, and in the relatively more sensitive cyanobacterium (blue-green alga) Microcystis aeruginosa, in which the toxicity threshold was 136 mg/L.

/AQUATIC SPECIES/ Aquatic invertebrates are less sensitive than fish to the toxicity of MIBK. ...The toxicity of MIBK was also measured in the green alga Scenedesmus quadricauda, in which the 8-day threshold for toxicity was 725 mg/L, and in the relatively more sensitive cyanobacterium (blue-green alga) Microcystis aeruginosa, in which the toxicity threshold was 136 mg/L.

Methyl isobutyl ketone has been reported found in Chinese quince

Methyl isobutyl ketone occurrence in plants(1).[Table#483]

Methyl isobutyl ketone is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and 2) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.

Methyl isobutyl ketone is an indirect food additive for use only as a component of adhesives.

U161; As stipulated in 40 CFR 261.33, when methyl isobutyl ketone, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

F003; When methyl isobutyl ketone is a spent solvent, it is classified as a hazardous waste from a nonspecific source (F003), as stated in 40 CFR 261.31, and must be managed according to State and/or Federal hazardous waste regulations.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Methyl isobutyl ketone is included on this list. Effective date 10/4/82; Sunset date 10/4/92.

A testing consent order is in effect for methyl isobutyl ketone for health effects testing. FR citation: 1/23/95.

Residues of methyl isobutyl ketone are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops or to raw agricultural commodities after harvest. Use: solvent. Limit: none.

Residues of methyl isobutyl ketone are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: solvent, cosolvent. Limit: none.

Residues of methyl isobutyl ketone are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to animals. Use: solvent, cosolvent. Limit: none.

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Methyl isobutyl ketone is produced, as an intermediate or final product, by process units covered under this subpart.

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Methyl isobutyl ketone is included on this list.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 5000 lb or 2270 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

(CA) CALIFORNIA 120 ug/L

(FL) FLORIDA 350 ug/L

(MA) MASSACHUSETTS 350 ug/L

(MN) MINNESOTA 300 ug/L

For more State Drinking Water Guidelines (Complete) data for Methyl isobutyl ketone (6 total), please visit the HSDB record page.

This study in male rats included corn oil (vehicle control), d-limonene (positive control, 300mg/kg), or MIBK (1000mg/kg) and female F-344 rats corn oil (vehicle control) or MIBK administered for ten consecutive days by oral gavage. MIBK elicited an increase in protein droplets, accumulation of alpha2u, and renal cell proliferation in male, but not female rats, responses characteristic of alpha2u-mediated nephropathy. MIBK produced identical histopathological changes in the male rat kidney when compared to d-limonene, an acknowledged inducer of alpha2u-nephropathy. MIBK did not induce any effects in female rats. The authors stated that the renal histopathology and the other measures of alpha2u accumulation provide additional weight of evidence to support the inclusion of MIBK in the category of chemicals exerting renal effects through an alpha2u-nephropathy-mediated mode-of-action.

Blood: initial fast phase = 12 minutes, then slow phase = 1 hour; [TDR, p. 886]

The absorption and metabolism of MIBK was studied in male Sprague-Dawley rats orally administered a single dose of 5 mmol/kg body weight of MIBK in corn oil, equivalent to 501 mg/kg body weight, by gavage. ... The plasma elimination half-life (t1/2) of MIBK ... was 2.529 hours ... .

In Guinea pigs serum half-lives and clearance times for methyl isobutyl ketone was 66 min and 6 hr respectively.

Methyl isobutyl ketone (MIBK) has recently been shown to potentiate the cholestasis induced by manganese-bilirubin (Mn-BR) or manganese (Mn) in rats. In this study, we investigated the effect of 4-methyl-2-pentanol (4MPOL) and 4-hydroxymethyl isobutyl ketone (4-OHMIBK), two major metabolites of MIBK, on these models of cholestasis. Dosages varying from 1.88 to 15 mmol/kg 4MPOL or 4-OHMIBK were administered once, 18 hr prior to the administration of a cholestatic Mn-BR combination. The cholestatic effect of the manganese-bilirubin combination was enhanced with dosages of 4MPOL of 3.75 mmol/kg and larger. On the other hand, dosages smaller than 15 mmol/kg of 4-OHMIBK did not potentiate the Mn-BR cholestasis. Daily pretreatment for 3 days resulted in an increased response to the cholestatic challenges of either Mn-BR or Mn alone. 4MPOL administered repetitively was a better potentiator than 4-OHMIBK with the Mn-BR model of cholestasis. However, with Mn alone, 4-OHMIBK proved to be more effective. 4MPOL and 4-OHMIBK per se were devoid of cholestatic properties, since the bile flow measured prior to the cholestatic challenge was not decreased and in some cases was significantly greater than that of vehicle-pretreated animals. These results show that MIBK metabolites can potentiate the cholestatic form of hepatotoxicity. /4-methyl-2-pentanol and 4-hydroxymethyl isobutyl ketone (metabolites)/

The absorption and metabolism of MIBK was studied in male Sprague-Dawley rats orally administered a single dose of 5 mmol/kg body weight of MIBK in corn oil, equivalent to 501 mg/kg body weight, by gavage. MIBK was rapidly absorbed into the systemic circulation following oral exposure, with a mean maximum plasma concentration (Cmax) of 0.644 mmol/L occurring at 0.25 hours [(time to maximum plasma concentration (tmax)] post-administration. MIBK was detected at very low levels (0.006 mmol/L) at 9 hours post-administration. The plasma levels of methyl isobutyl carbinol (MIBC) were very low (<0.012 mmol/L) all over the study. The major material in the blood was 4-hydroxymethyl-4-methyl-2-pentanone (referred to as HMP based on the chemical name) [i.e., diacetone alcohol (DAA], with a Cmax of 2.03 mmol/L at 9 hours and remained detectable at 12 hours post-dosing. Neither MIBK nor MIBC were detectable in 12-hour samples. No compounds other than HMP and MIBK were detected in the blood. The 12-hour area under the plasma concentration time curve (AUC0-12 h) for MIBK, MIBC and HMP were 0.089, 3.558 and 17, 436 mmol/L/hour, respectively. HMP and MIBK represented 79% and 20% of the total AUC, respectively. The plasma elimination half-life (t1/2) of MIBK and HMP were 2.529 and 4.831 hours, respectively. Based on the results of this study, MIBK is rapidly absorbed into the blood in rats following oral exposure and is rapidly and extensively metabolized to HMP (the major metabolite in blood after 3 hours).

Methyl isobutyl carbinol (MIBC) is an oxygenated solvent that is metabolized to methylisobutyl ketone (MIBK) and then to 4-hydroxymethyl-4-methyl-2-pentanone (HMP). Plasma levels of MIBC, MIBK and HMP were determined up to 12 hr after a single oral 5 mmol/kg dose of MIBC or MIBK to male rats. The major material in the plasma in both cases was HMP, with similar areas-under-the-curve (AUC) and C(max) at 9 hr after dosing. MIBK plasma levels and AUC were also comparable after MIBK or MIBC administration. MIBC AUC was only about 6% of the total material in the blood after MIBC, and insignificant after MIBK administration. No other metabolites were detected in the plasma under the analytical conditions used. The extent of metabolism of MIBC to MIBK, by comparing combined AUCs for MIBK and HMP, was at least 73%. ...

The metabolic fate of methyl n-butyl ketone (MnBK) and its isomer methyl isobutyl ketone (MiBK) was studied in mice. The concentrations of both ketones and their metabolites in blood and brain were measured at different time intervals after their administration. The principal metabolites of ... MiBK were 4-methyl-2-pentanol (4-MPOL) and 4-hydroxy-4 methyl-2-pentanone (HMP). .... The administration of 4-methyl-2-pentanol resulted in the appearance of MiBK and HMP. The administration of HMP did not result in the appearance of MiBK or 4-MPOL. ....

For more Metabolism/Metabolites (Complete) data for Methyl isobutyl ketone (7 total), please visit the HSDB record page.

Methyl isobutyl ketone (MIBK) is a solvent used in numerous products and processes and may be present in the air of the workplace as a vapor. The American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value-time-weighted average (TLV-TWA) and TLV-short term exposure limit (TLV-STEL) for MIBK are 50 and 75 ppm, respectively. These workplace air concentration limits were set to protect workers from irritation, neurasthenic symptoms and possible adverse effects to their livers and kidneys. A recent revision of the ACGIH limit value has been proposed, to reduce the current TLV-TWA to 30 ppm. This article predicts the kinetics and accumulation of MIBK in humans exposed repeatedly in various exposure scenarios (8, 12, and 24 hr/day for 7 days) to the current ACGIH TLV-TWA of 50 ppm. The kinetic parameters of the model were derived from published human time-course blood MIBK data from a single 2 hr inhalation exposure to 48.9 ppm MIBK. The model correctly simulated single exposure experimental data with a rapid rise in blood concentration to 1.06 ug/mL within 1 hr and approached >or=99% steady-state blood level in 4 hr of exposure. MIBK was predicted to be rapidly eliminated from blood after terminating the exposure, reaching 0.53 ug/mL and 0.13 ug/mL within 0.5 and 2 hr post-exposure, respectively. Within 4h after the termination of exposure, blood concentration would be expected to <1% of the steady-state concentration. On the basis of these results, it is concluded that accumulation of MIBK in workers due to repeated inhalation exposure is not likely to occur at the current TLV-TWA concentration of 50 ppm.

Methyl isobutyl ketone /was reported/ in human maternal blood samples collected immediately after delivery, indicating the potential for the compound to enter the umbilical cord and cross the placenta.

Methyl isobutyl ketone was detected in the brain, liver, lung, vitreous fluid, kidney, and blood in two workers who died after exposure to several organic solvents during spray painting. One died from a fall and the other died of cerebral edema 9 hours later. Tissue concentrations (mg/100 g) were reported to be: case 1 - brain, 0.25; liver, 0.49; lung, 0.43; vitreous fluid, 0.52; kidney, 0.24; and femoral blood, 0.14; and case 2 - brain, 0.06; liver, 0.22; lung, 0.11; vitreous fluid, 0.02; kidney, 0.08; and heart blood, 0.04.

Human volunteers (98 men and women) were exposed to 100 ppm (410 mg/cu m) methyl isobutyl ketone for 4 hours in an environmental chamber. Steady-state blood concentrations of methyl isobutyl ketone were attained after 2 hours of exposure. Blood and breath samples collected 90 minutes after exposure indicated that most of the absorbed compound had been eliminated from the body.

For more Absorption, Distribution and Excretion (Complete) data for Methyl isobutyl ketone (11 total), please visit the HSDB record page.

CIR ingredient: MIBK

Methyl isobutyl ketone is used as a solvent for gums, resins, paints, varnishes, lacquers, and nitrocellulose, as an alcohol denaturant, in the extraction of rare metals, and as a synthetic flavoring adjuvant.

Used as a solvent in the paint, synthetic resin, adhesive, aircraft, and pharmaceutical manufacturing industries; [ACGIH]

Textiles (Fiber & Fabric Manufacturing) [Category: Industry]

Solvent for gums, resins, nitrocellulose, paints, varnishes, and lacquers. Denaturant for rubbing alcohol. In manufacture of methyl amyl alcohol. In dry-cleaning preparations.

... Extraction processes including extraction of uranium from fission products; organic synthesis ... .

(1984) 7.22X10+9 g

(1987) 5.90X10+5 lb

(1988) 1.92X10+6 lb

1997 exports amounted to 46 million pounds and averaged 40 million pounds annually in the 1994-97 period

2001 exports amounted to 47 million pounds; 2002 exports amounted to 53 million pounds

(1984) 9.31X10+9 g

(1986) 1.25X10+7 lb

1997 imports amounted to 23 million pounds and averaged 20 million pounds annually in the 1994-97 period

2001 imports amounted to 26 million pounds; 2002 imports amounted to 32 million pounds

2023: 100,000,000 - <250,000,000 lb

(1984) 6.50X10+10 g

(1987) 1.51X10+8 lb

(1988) 2.0X10+8 lb

In 1987 ... US production was 70,000 tons.

For more U.S. Production (Complete) data for Methyl isobutyl ketone (11 total), please visit the HSDB record page.

65% AS SOLVENT FOR PROTECTIVE COATINGS, 5% AS SOLVENT FOR RARE METAL EXTRACTION; 5% EXPORTED; 25% FOR MISC APPLICATIONS INCLUDING DEWAXING OF MINERAL OILS AND IN THE MANUFACTURE OF ANTIBIOTICS (1971)

NITROCELLULOSE LACQUERS, 25%; OTHER COATINGS, INKS, LACQUERS, 30%; SOLVENT EXTRACTION, 10%; MIBC, 10%; METALURGICAL, 5%; EXPORT, 15%; MISC, 5% (1980)

CHEMICAL PROFILE: Methyl isobutyl ketone. Demand: 1986: 145 million lb; 1987: 148 million lb; 1991 /projected/: 155 million lb. (Includes exports; in addition, 12.5 million lb were imported in 1986).

Demand 1995: 175 million pounds; 2000: 175 million pounds.

For more Consumption Patterns (Complete) data for Methyl isobutyl ketone (9 total), please visit the HSDB record page.

Mild hydrogenation of mesityl oxide.

By hydrogenation of mesityl oxide over nickel at 160-190 °C, ... .

In /a/ ... three-step process acetone undergoes alkali-catalyzed condensation in the first step to form diacetone alcohol. Dehydration of the latter to mesityl oxide takes place in the liquid phase at 90-130 °C over an acid catalyst, such as phosphoric or sulfuric acid, with high selectivity. Selective hydrogenation of the carbon-carbon double bond in mesityl oxide to give 4-methyl-2-pentanone may be carried out in both the liquid phase and the gas phase with various catalysts, preferably palladium. ... Dehydration and hydrogenation can also be combined into a single process step.

... /A/ two-step process is less important industrially. Acetone is converted in a single step to mesityl oxide, which is then hydrogenated to 4-methyl-2-pentanone in a second step. Catalysts such as copper chromite or zirconium phosphate are used for the condensation, and palladium on aluminum oxide for the hydrogenation. 4-Methyl-2-pentanol is formed as a byproduct.

For more Methods of Manufacturing (Complete) data for Methyl isobutyl ketone (7 total), please visit the HSDB record page.

Grade: Technical, 98.5%.

/The NF grade/ ... contains not less than 99% of methyl isobutyl ketone.

MIBK IS FREQUENTLY BLENDED WITH METHYL ETHYL KETONE IN HIGH SOLIDS LACQUERS

4-Methyl-2-pentanone is available with a purity of >99%.

Cosmetics product ingredient: Methyl isobutyl ketone (MIBK) (Isopropyl acetone)

Information on 95 consumer products that contain Methyl isobutyl ketone in the following categories is provided:

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Cosmetics -> Solvent; Denaturant

Methyl Isobutyl Ketone (MIBK)

A chemical, other than a List I chemical, specified by regulation that, in addition to legitimate uses, is used in manufacturing a controlled substance in violation of the Act. (21 eCFR 1310.02)