Toxicity Profiles
Condensed Toxicity Summary for METHYL ISOBUTYL KETONE
NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.
July 1995
Prepared by Rosmarie A. Faust, Ph.D., Chemical Hazard Evaluation and Communication Program, Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, *, Oak Ridge, Tennessee.
Prepared for OAK RIDGE RESERVATION ENVIRONMENTAL RESTORATION PROGRAM.
*Managed by Lockheed Martin Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.
Methyl isobutyl ketone (MIBK) (CAS Reg. No. 108-10-1), a clear liquid with a characteristic odor, is a ketone with the chemical formula of CH3COCH2CH(CH3)2 (Budavari et al. 1989). It is widely used as a solvent for various paints, lacquers, varnishes, adhesives, and rubber cements and as an extractant for mineral oils. The most likely exposures to MIBK are by inhalation of the vapors and by skin contact (NIOSH 1978). MIBK is released to the environment in effluents and emissions from its manufacturing and use facilities, in automotive exhaust gases, and from disposal of consumer products containing MIBK (HSDB 1993).
MIBK is readily absorbed following inhalation (Hjelm et al. 1990) and, by analogy to other ketones (Parmeggiani 1983), is expected to be absorbed through the skin. Metabolism of MIBK involves an oxidative hydroxylation, followed by reduction to the secondary alcohol (DiVincenzo et al. 1976).
Targets for MIBK toxicity appear to be the central nervous system, gastrointestinal tract, liver, kidneys, fetus, and mucous membranes. At high concentrations, MIBK is a central nervous system depressant, inducing ataxia, narcosis, and death in experimental animals (Krasavage et al. 1982, Specht et al. 1940, Specht 1938). Human exposure to lower concentrations has resulted in central nervous system effects such as headache, weakness, vertigo, insomnia, and somnolence. Gastrointestinal effects including nausea, vomiting, loss of appetite, heart burn, and intestinal pain were reported also (Linari et al. 1964, Hjelm et al. 1990). MIBK has been shown to exert synergistic effects on n-hexane neurotoxicity in hens (Abou-Donia et al. 1985). Although MIBK is a central nervous system depressant, peripheral neuropathy similar to that induced by other ketones has not been documented.
Slightly enlarged livers were reported in some workers exposed to MIBK in workplace air (Linari et al. 1964). Increased liver weights were also reported in male and female rats orally exposed for 90 days (Microbiological Associates 1986) and in rats and mice exposed by inhalation for periods ranging from 2 to 14 weeks (Phillips et al. 1987, MacEwen et al. 1971). MIBK has been shown to potentiate carbon tetrachloride-induced liver injury in rats (Pilon et al. 1988). In male and female rats, subchronic oral exposure produced increased kidney weights and nephropathy (Microbiological Associates 1986) and subchronic inhalation exposure resulted in hyalin droplet degeneration of the proximal tubules and some reversible tubular necrosis (Phillips et al. 1987). These effects were not seen in other species tested. Rats and mice exposed by inhalation to high concentrations of MIBK (3000 ppm) during organogenesis demonstrated maternal and fetal toxicity but no teratogenicity (Bushy Run Research Center 1984).
Exposure to MIBK has been shown to irritate the conjunctiva and mucous membranes of the nose and throat (Hjelm et al. 1990, Elkins 1959). MIBK may also produce dermatitis, with skin lesions varying from erythema to small areas of peeling (Linari et al. 1964).
The U.S. Environmental Protection Agency (EPA) (1994) calculated an oral reference dose (RfD) of 8E-1 mg/kg/day for subchronic exposure and 8E-2 mg/kg/day for chronic exposure to MIBK, based on a no-observed-adverse-effect level (NOAEL) of 250 mg/kg/day from a 13-week gavage study with rats (Microbiological Associates 1986). Lethargy, increased liver and kidney weights, and increased urinary protein levels were identified as critical effects. The chronic oral
RfD has been withdrawn from EPA's Integrated Risk Information System (IRIS) pending further review (EPA 1995). EPA (1994) calculated an inhalation reference concentration (RfC) of 8E-1 mg/m3 for subchronic exposure and 8E-2 mg/m3 for chronic exposure to MIBK, based on a no-observed-effect level (NOEL) of 50 ppm from a 90-day inhalation study with rats (Union Carbide Corporation 1983). Increased liver weights and kidney effects were identified as critical effects. The inhalation RfC is currently under review by the RfD/RfC Work Group (EPA 1995).
No studies were available to evaluate the carcinogenicity of MIBK. Furthermore, EPA has not
assigned a weight-of-evidence classification for carcinogenicity.
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Last Updated 10/31/97