Tertiary-Butanol: A toxicological review

Abstract

Tert-Butanol is an important intermediate in industrial chemical synthesis, particularly of fuel oxygenates. Human exposure to tert-butanol may occur following fuel oxygenate metabolism or biodegradation. It is poorly absorbed through skin, but is rapidly absorbed upon inhalation or ingestion and distributed to tissues throughout the body. Elimination from blood is slower and the half-life increases with dose. It is largely metabolised by oxidation via 2-methyl-1,2-propanediol to 2-hydroxyisobutyrate, the dominant urinary metabolites. Conjugations also occur and acetone may be found in urine at high doses. The single-dose systemic toxicity of tert-butanol is low, but it is irritant to skin and eyes; high oral doses produce ataxia and hypoactivity and repeated exposure can induce dependence. Tert-Butanol is not definable as a genotoxin and has no effects specific for reproduction or development; developmental delay occurred only with marked maternal toxicity. Target organs for toxicity clearly identified are kidney in male rats and urinary bladder, particularly in males, of both rats and mice. Increased tumour incidences observed were renal tubule cell adenomas in male rats and thyroid follicular cell adenomas in female mice and, non-significantly, at an intermediate dose in male mice. The renal adenomas were associated with α_2u-globulin nephropathy and, to a lesser extent, exacerbation of chronic progressive nephropathy. Neither of these modes of action can function in humans. The thyroid tumour response could be strain-specific. No thyroid toxicity was observed and a study of hepatic gene expression and enzyme induction and thyroid hormone status has suggested a possible mode of action.

Keywords::

• Acetone
• ETBE
• ethyl tertiary-butyl ether
• formaldehyde
• metabolism
• methyl tertiary-butyl ether
• MTBE
• mutagens
• oxygenates reproductive toxicity
• rodent carcinogens
• tertiary-butyl alcohol
• toxicity

Acknowledgements

I gratefully acknowledge the useful suggestions made by Willem Faber on the fate of acetone.

Declaration of interest

This review was supported under contract to LyondellBasell Industries, Houston, Texas. The author has no financial interest in this company or associated companies or any other commercial or governmental organization. LyondellBasell Industries supplied unpublished reports as requested by the author, but played no part in the formulation of the opinions expressed in this paper. The author provides consulting services on toxicological issues to both public and private organizations. The author alone prepared the paper and is responsible for the conclusions that have been presented.