a-Hydroxyisobutyric Acid (from MTBE)

α-Hydroxyisobutyric Acid is a major urinary metabolite of the industrial solvent methyl tert-butyl ether (MTBE).

MTBE was a gasoline additive discontinued in the early 2000’s used to reduce automobile emissions. Due to significant ground water leakage from storage tanks, ongoing exposure to MTBE exists in ground water. There is also data available on levels of MTBE in ambient air.

Urinary α-hydroxyisobutryic acid is a marker of recent MTBE exposure. Although, MTBE was initially designated as “noncarcinogenic”, recent studies suggest some interesting clinical associations. Exposure to MTBE has been linked to type 2 diabetes as a result of disrupted zinc homeostasis and glucose tolerance. There are also clinical associations with autism, DNA oxidative damage, and methylation defects. Studies on cancer, reproductive abnormalities, nonalcoholic fatty liver, and neurotoxicity have been either negative or inconclusive thus far.

References:

- Organization WH. Methyl tertiary-butyl ether (MTBE) in drinkingwater, background document for development of WHO Guidelines for Drinking-Water Quality. World Health Organization, Geneva(WHO/SDE/WSH/0508/122). 2005.

- Amberg A, Rosner E, Dekant W. Toxicokinetics of methyl tert-butyl ether and its metabolites in humans after oral exposure. Toxicol Sci. 2001;61(1):62-67.

- Saeedi A, Fardid R, Khoshnoud MJ, Kazemi E, Omidi M, Mohammadi-Bardbori A. Disturbance of zinc and glucose homeostasis by methyl tert-butyl ether (MTBE); evidence for type 2 diabetes. Xenobiotica. 2017;47(6):547-552.

- Andreoli R, Spatari G, Pigini D, et al. Urinary biomarkers of exposure and of oxidative damage in children exposed to low airborne concentrations of benzene. Environ Res. 2015;142:264- 272.

- Kalkbrenner AE, Windham GC, Zheng C, et al. Air Toxics in Relation to Autism Diagnosis, Phenotype, and Severity in a U.S. FamilyBased Study. Environ Health Perspect. 2018;126(3):037004- 037004.

- Salimi A, Vaghar-Moussavi M, Seydi E, Pourahmad J. Toxicity of methyl tertiary-butyl ether on human blood lymphocytes. Environ Sci Pollut Res. 2016;23(9):8556-8564.

- Rota F, Conti A, Campo L, et al. Epigenetic and Transcriptional Modifications in Repetitive Elements in Petrol Station Workers Exposed to Benzene and MTBE. Int J Environ Res Pub Health. 2018;15(4):735.

- O’Callaghan JP, Daughtrey WC, Clark CR, Schreiner CA, White R. Health assessment of gasoline and fuel oxygenate vapors: neurotoxicity evaluation. Reg Toxicol Pharmacol. 2014;70(2 Suppl):S35-42.

- Gray TM, Steup D, Roberts LG, et al. Health assessment of gasoline and fuel oxygenate vapors: reproductive toxicity assessment. Reg Toxicol Pharmacol. 2014;70(2 Suppl):S48-57.

- Yang J, Wei Q, Peng X, Peng X, Yuan J, Hu D. Relationship between methyl tertiary butyl ether exposure and non-alcoholic fatty liver disease: a cross-sectional study among petrol station attendants in southern China. Int J Environ Res Pub Health. 2016;13(10):946.