Toxicokinetics of ethers used as fuel oxygenates

Dekant, W.; Bernauer, Ulrike; Rosner, Elisabeth; Amberg, Alexander

doi:10.1016/s0378-4274(00)00284-8

Cited by 29 publications

(18 citation statements)

References 32 publications

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“…Previous pharmacokinetics studies have indicated that MTBE was rapidly absorbed by inhalation and ingestion in rats and mice and then eliminated via both exhalation and urine excretion (Dekant et al, 2001). The previous experiments using radiolabeled MTBE showed that excretion of MTBE metabolites in mice via urine was essentially completed after 48 h. However, our study has shown that MTBE-DNA adducts persist even 21 days after a single dosing.…”

Section: Resultscontrasting

confidence: 49%

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Formation of MTBE-DNA adducts in mice measured with accelerator mass spectrometry

Wang

et al. 2005

Environ. Toxicol.

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Methyl tert-butyl ether (MTBE) is a gasoline oxygenate and antiknock additive substituting for lead alkyls currently in use worldwide. Previous studies have shown that MTBE at very high doses induces tumors in rodents. The aim of the present study was to examine directly the binding ability of MTBE onto DNA, demonstrating its potential genotoxicity. MTBE-DNA adducts and their decay kinetics in mice have been measured by using doubly 14C-labeled MTBE with an advanced, ultrasensitive technique: accelerator mass spectrometry (AMS). It was found that MTBE definitely formed adducts with DNA in mouse lung, liver, and kidney in a log/log linear dose-response relationship. The distribution sequence of DNA adducts in these tissues is: lung > liver > kidney. The level of MTBE-DNA adducts peaked at 12 h postadministration in the lung and peaked at 6 h postadministration in the liver. Then the adducts declined rapidly until 5 days postadministration and thereafter declined much more slowly. To our knowledge, this is the first report on DNA adduction with MTBE in vivo. The mechanism of the formation of MTBE-DNA adducts also is discussed.

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Section: Resultscontrasting

confidence: 49%

“…Formaldehyde is most likely oxidized to formic acid in the liver. TBA is further oxidized to 2-methyl-1, 2-propanediol, and 2-hydroxyisobutyrate (Dekant, 2001). The doubly 14 C-labeled MTBE [(CH 3 ) 3 14 CÀ ÀOÀ À 14 CH 3 ] enabled us to detect all its metabolites that formed adducts with DNA.…”

Section: Resultsmentioning

confidence: 99%

Formation of MTBE-DNA adducts in mice measured with accelerator mass spectrometry

Wang

et al. 2005

Environ. Toxicol.

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“…Regarding 2-HIBA, two recent studies reported that this compound is constitutively present in human urine and serum [30], [31]. Moreover, 2-HIBA is the major urinary metabolite in humans following exposure to the gasoline additives methyl- tert .butyl ether and ethyl- tert .butyl ether [32], [33]. Elevated plasma concentrations of 2-HIBA were observed in patients with type 2 diabetes mellitus, possibly due to disturbances in fatty acid metabolism [34].…”

Section: Discussionmentioning

confidence: 99%

Optimized Metabolomic Approach to Identify Uremic Solutes in Plasma of Stage 3–4 Chronic Kidney Disease Patients

et al. 2013

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BackgroundChronic kidney disease (CKD) is characterized by the progressive accumulation of various potential toxic solutes. Furthermore, uremic plasma is a complex mixture hampering accurate determination of uremic toxin levels and the identification of novel uremic solutes.MethodsIn this study, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy, following three distinct deproteinization strategies, to determine differences in the plasma metabolic status of stage 3–4 CKD patients and healthy controls. Moreover, the human renal proximal tubule cell line (ciPTEC) was used to study the influence of newly indentified uremic solutes on renal phenotype and functionality.ResultsProtein removal via ultrafiltration and acetonitrile precipitation are complementary techniques and both are required to obtain a clear metabolome profile. This new approach, revealed that a total of 14 metabolites were elevated in uremic plasma. In addition to confirming the retention of several previously identified uremic toxins, including p-cresyl sulphate, two novel uremic retentions solutes were detected, namely dimethyl sulphone (DMSO2) and 2-hydroxyisobutyric acid (2-HIBA). Our results show that these metabolites accumulate in non-dialysis CKD patients from 9±7 µM (control) to 51±29 µM and from 7 (0–9) µM (control) to 32±15 µM, respectively. Furthermore, exposure of ciPTEC to clinically relevant concentrations of both solutes resulted in an increased protein expression of the mesenchymal marker vimentin with more than 10% (p<0.05). Moreover, the loss of epithelial characteristics significantly correlated with a loss of glucuronidation activity (Pearson r = −0.63; p<0.05). In addition, both solutes did not affect cell viability nor mitochondrial activity.ConclusionsThis study demonstrates the importance of sample preparation techniques in the identification of uremic retention solutes using 1H-NMR spectroscopy, and provide insight into the negative impact of DMSO2 and 2-HIBA on ciPTEC, which could aid in understanding the progressive nature of renal disease.

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“…Increased oxygen content is required to improve combustion efficiency and reduce harmful tailpipe emissions, such as CO, O 3 , etc., from motor vehicles. To achieve the specified oxygen content requirements, 5-15% MTBE in gasoline is required [2].…”

Section: Introductionmentioning

confidence: 99%

Application of artificial neural networks for modeling of the treatment of wastewater contaminated with methyl tert-butyl ether (MTBE) by UV/H2O2 process

Salari

Daneshvar

Aghazadeh

et al. 2005

Journal of Hazardous Materials

134

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Toxicokinetics of ethers used as fuel oxygenates

Cited by 29 publications

References 32 publications

Formation of MTBE-DNA adducts in mice measured with accelerator mass spectrometry

Formation of MTBE-DNA adducts in mice measured with accelerator mass spectrometry

Optimized Metabolomic Approach to Identify Uremic Solutes in Plasma of Stage 3–4 Chronic Kidney Disease Patients

Application of artificial neural networks for modeling of the treatment of wastewater contaminated with methyl tert-butyl ether (MTBE) by UV/H2O2 process

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