Environmental health criteria 65: Butanols: Four isomers: 1-butanol, 2-butanol, tert-butanol, isobutanol
Isobutanol (2 methyl propanol) is a inflammable colourless liquid with a sweet odour similar to that of amyl alcohol. It has a boiling point of 108 C, a water solubility Of 8.7%, and its n-octanol/water partition coefficient is 0.83. Its vapour is 2.6 times denser than air. It occurs naturally as a product of fermentation and is synthesized from petrochemicals. It is used as an organic solvent, as a plasticizer, in the manufacture of isobutyl esters, in perfumes, and as a flavouring agent. Human exposure is primarily occupational. Exposure of the general population will mainly be from its natural occurrence in food and its use as a flavouring agent, but may also result from industrial emissions. Isobutanol is readily biodegradable and does not bioaccumulate. It is not directly toxic for fish, crustacea, amphibia, or algae (Fish, 96-h LC50 = 1000-3000; Daphnia 24-h EC50 = 1250 and Green algae, 8-day NOAEL = 350 mg/l). Protozoa will tolerate levels of isobutanol likely to be found in the environment (48-h NOAEL = 22 mg/l). Isobutanol should be managed in the environment as a slightly toxic compound. It poses an indirect hazard for the aquatic environment, because it is readily biodegraded, which may lead to oxygen depletion. In animals, isobutanol is absorbed through the skin, lungs, and gastrointestinal tract. It is metabolized by alcohol dehydrogenase to isobutyric acid via the aldehyde and may enter the tricarboxylic acid cycle. Small amounts of isobutanol are excreted unchanged (0.5% of the dose), or as the glucuronide (5% of the dose) in the urine. In rabbits, metabolites found in the urine include acetaldehyde, acetic acid, isobutylaldehyde, and isovaleric acid. Oral LD50 values (2.5 - 3.1 g/kg body weight) and the inhalation LC50 (19.2 g/m3) in rats classifies isobutanol as slightly toxic according to Hodge and Sterner. The acute toxic effects are alcoholic intoxication and narcosis. Isobutanol is severely irritating to the eyes and moderately irritating to the skin. A group of rats given a solution of isobutanol (1 mol/litre) as their sole drinking liquid for 4 months did not show any adverse effects on the liver, while another group given a 2 mol/litre solution as their sole drinking liquid for 2 months showed reductions in rat, glycogen, RNA content, and overall size of the cells in the liver. Continuous inhalation exposure of rats to 3 mg/m3 for 4 months resulted in depression of leg withdrawal response to electrical stimulation, and minor changes in formed elements of the blood and serum enzymes. The estimated no-observed-adverse-effect level was 0.1 mg/m3. In a lifetime carcinogenicity study, groupS of rats received isobutanol subcutaneously (0.05 ml/kg, twice a week) or orally (0.2 ml/kg body weight twice a week). The animals exhibited toxic liver damage ranging from steatosis to cirrhosis. Animals showing malignant tumours totalled 8 in the subcutaneous group, 3 in the oral group, and O in the control group. The majority of treated animals also showed hyperplasia of blood-forming tissues. From the animal studies available, it is not possible to determine a no-observed-adverse-effect level for long-term exposure. No adequate data are available to assess the mutagenicity or teratogenicity of isobutanol or effects on reproduction. The only reported observations in man relate to the production of vertigo under conditions of severe and prolonged exposure to vapour mixtures of isobutanol and l-butanol. Thus, it is not possible to attribute the vertigo to a single cause.