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Biotransformation of MTBE, ETBE, and TAME after inhalation or ingestion in rats and humans.

Abstract

The biotransformation of methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME) was studied in humans and in rats after inhalation of 4 and 40 ppm of MTBE, ETBE, and TAME, respectively, for 4 hours, and the biotransformation of MTBE and TAME was studied after ingestion exposure in humans to 5 and 15 mg in water. tert-Butyl alcohol (TBA), a TBA conjugate, 2-methyl-1,2-propanediol, and 2-hydroxyisobutyrate were found to be metabolites of MTBE and ETBE. tert-Amyl alcohol (TAA), free and glucuronidated 2-methyl-2,3-butanediol (a glucuronide of TAA), 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3-methyl butyrate were found to be metabolites of TAME. After inhalation, MTBE, ETBE, and TAME were rapidly taken up by both rats and humans; after termination of exposure, clearance from blood of the ethers by exhalation and biotransformation to urinary metabolites occurred with half-times of less than 7 hours in rats and humans. Biotransformation of MTBE and ETBE was similar in humans and rats after inhalation exposure. 2-Hydroxyisobutyrate was recovered as a major product in urine. All metabolites of MTBE and ETBE excreted with urine were eliminated with half-times of less than 20 hours. Biotransformation of TAME was qualitatively similar in rats and humans, but the metabolic pathways were different. In humans, 2-methyl-2,3-butanediol, 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3methyl butyrate were recovered as major urinary products. In rats, however, 2-methyl-2,3-butanediol and its glucuronide were major TAME metabolites recovered in urine. After ingestion of MTBE and TAME, both compounds were rapidly absorbed from the gastrointestinal tract. Hepatic first-pass metabolism of these ethers was not observed, and a significant part of the administered dose was transferred into blood and cleared by exhalation. Metabolic pathways for MTBE and TAME and kinetics of excretion were identical after ingestion and inhalation exposures. Results of studies presented here suggest (1) that excretion of MTBE, ETBE, and TAME in rats and humans is rapid, (2) that biotransformation and excretion of MTBE and ETBE are identical in rats, and (3) that biotransformation and excretion of TAME is quantitatively different in rats and humans.

Authors+Show Affiliations

Department of Toxicology, University of Würzburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11504147

Citation

Dekant, W, et al. "Biotransformation of MTBE, ETBE, and TAME After Inhalation or Ingestion in Rats and Humans." Research Report (Health Effects Institute), 2001, pp. 29-71; discussion 95-109.
Dekant W, Bernauer U, Rosner E, et al. Biotransformation of MTBE, ETBE, and TAME after inhalation or ingestion in rats and humans. Res Rep Health Eff Inst. 2001.
Dekant, W., Bernauer, U., Rosner, E., & Amberg, A. (2001). Biotransformation of MTBE, ETBE, and TAME after inhalation or ingestion in rats and humans. Research Report (Health Effects Institute), (102), 29-71; discussion 95-109.
Dekant W, et al. Biotransformation of MTBE, ETBE, and TAME After Inhalation or Ingestion in Rats and Humans. Res Rep Health Eff Inst. 2001;(102)29-71; discussion 95-109. PubMed PMID: 11504147.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biotransformation of MTBE, ETBE, and TAME after inhalation or ingestion in rats and humans. AU - Dekant,W, AU - Bernauer,U, AU - Rosner,E, AU - Amberg,A, PY - 2001/8/16/pubmed PY - 2002/1/5/medline PY - 2001/8/16/entrez SP - 29-71; discussion 95-109 JF - Research report (Health Effects Institute) JO - Res Rep Health Eff Inst IS - 102 N2 - The biotransformation of methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME) was studied in humans and in rats after inhalation of 4 and 40 ppm of MTBE, ETBE, and TAME, respectively, for 4 hours, and the biotransformation of MTBE and TAME was studied after ingestion exposure in humans to 5 and 15 mg in water. tert-Butyl alcohol (TBA), a TBA conjugate, 2-methyl-1,2-propanediol, and 2-hydroxyisobutyrate were found to be metabolites of MTBE and ETBE. tert-Amyl alcohol (TAA), free and glucuronidated 2-methyl-2,3-butanediol (a glucuronide of TAA), 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3-methyl butyrate were found to be metabolites of TAME. After inhalation, MTBE, ETBE, and TAME were rapidly taken up by both rats and humans; after termination of exposure, clearance from blood of the ethers by exhalation and biotransformation to urinary metabolites occurred with half-times of less than 7 hours in rats and humans. Biotransformation of MTBE and ETBE was similar in humans and rats after inhalation exposure. 2-Hydroxyisobutyrate was recovered as a major product in urine. All metabolites of MTBE and ETBE excreted with urine were eliminated with half-times of less than 20 hours. Biotransformation of TAME was qualitatively similar in rats and humans, but the metabolic pathways were different. In humans, 2-methyl-2,3-butanediol, 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3methyl butyrate were recovered as major urinary products. In rats, however, 2-methyl-2,3-butanediol and its glucuronide were major TAME metabolites recovered in urine. After ingestion of MTBE and TAME, both compounds were rapidly absorbed from the gastrointestinal tract. Hepatic first-pass metabolism of these ethers was not observed, and a significant part of the administered dose was transferred into blood and cleared by exhalation. Metabolic pathways for MTBE and TAME and kinetics of excretion were identical after ingestion and inhalation exposures. Results of studies presented here suggest (1) that excretion of MTBE, ETBE, and TAME in rats and humans is rapid, (2) that biotransformation and excretion of MTBE and ETBE are identical in rats, and (3) that biotransformation and excretion of TAME is quantitatively different in rats and humans. SN - 1041-5505 UR - https://www.unboundmedicine.com/medline/citation/11504147/Biotransformation_of_MTBE_ETBE_and_TAME_after_inhalation_or_ingestion_in_rats_and_humans_ DB - PRIME DP - Unbound Medicine ER -