Methyl isobutyl ketone

CAS RN: 108-10-1

Toxicity Summary

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.
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