Description: Das Projekt "Vergleichende Untersuchung zur biologischen Umsetzung von Methyl-Tert. Butyl Ether, Butyl Ether, Ethyl-Tert. Butyl Ether, Tert.-Amyl Methyl Ether und Diisopropyl Ether in Ratten und Menschen" wird vom Umweltbundesamt gefördert und von Universität Würzburg, Institut für Pharmakologie und Toxikologie durchgeführt. This study intends to generate comparative data on the biotransformation of ethers added to gasoline in humans and in rats. The proposed experiments will compare the biotransformation of methyl-tert. butyl ether, ethyl-tert. butyl ether and tert.-amyl methyl ether in rats and humans after inhalation exposure. The structures of formed metabolites will be elucidated and their time and exposure concentration dependent excretion will be quantified. The metabolism of these ethers will also be studied in vitro in rat and human liver microsomes to identify the cytochrome P450 enzymes responsible for biotransformation focusing on possible interindividual differences in human biotrans-formation. The obtained data will permit a comparison of the relative excretion of metabolites in humans and rats and interindividual differences in human biotransformation of these ethers. The obtained results will thus serve as a basis for risk comparisons and should contribute to further characterisation of the human risk of exposure to these ethers. The in vivo biotransformation of the ethers will be studied in a dynamic exposure chamber and 6 individuals (three males and three females) will be exposed to 2 concentrations of each of the ethers (5 and 40 ppm for 4 hours). Blood and urine will be collected before the exposure and at predetermined intervals over 48 h after the end of the exposure. Five rats of each sex will be exposed to the ethers under identical conditions. Parent ethers and relevant metabolites will be quantified in the blood samples and relevant metabolites in the urine samples collected. Ether metabolites in urine will be identified by NMR studying the biotransformation of 13C- labelled ethers and quantified by GC/MS. In vitro, thel beiotransformation of the ethers will be studied in liver microsomes (a human liver bank characterized for cytochrome P450 activities with samples from 16 donors is available) and the cytochrome P450 enzyme responsible for the oxidation of the ethers (and potential metabolites) will be identified by the use of P450 enzyme specific inhibitors, inhibitory antibodies and correlation of the rates of ether metabolism with the rates of oxidation of P450 enzyme specific substrates. This laboratory has completed similar studies on CFC-replacements and on trichloroethene (sponsored by the German Occupational Health Council) and is presently using an identical approach comparing the biotransformation of perchloroethene (sponsored by the US EPA).
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Origin: /Bund/UBA/UFORDAT
Tags: Antioxidationsmittel ? Benzin ? MTBE ? Kraftstoff ? Tetrachlorethen ? Gesundheitsgefährdung ? Inhalation ? Oxyfuel-Verfahren ? Ether ? Urin ? Biochemie ? Mikrosom ? Schadstoffwirkung ? Zusatzstoff ? Cytochrom ? Urinprobe ? Blutprobe ? Antikörper ? Enzym ? Expositionsdauer ? Pharmakologie ? Ratte ? Schadstoffexposition ? Stoffwechselprodukt ? Arbeitsschutz ? Hemmstoff ? Biotransformation ? Medizin ? Mensch ? Blut ? Redoxpotential ? Risikoanalyse ? Organischer Schadstoff ? Studie ? Tierversuch ? Toxikologie ? Vergleichsanalyse ? Exkretion ? Daten ? Stoffwechsel ? Risiko ? Butylether ? CASNR-1634-04-4 ? Butyl-Ether ? CASNR-637-92-3 ? CASNR-994-05-8 ? Diisopropylether ? Ethyl-tert.-butylether ? In-Vivo ? Isopropyl-Ether ? Methyl-Ether ? Schadstoffnachweis ? tert.-Amyl-methylether ? CASNR-108-20-3 ? CASNR-142-96-1 ?
Region: Bayern
Bounding boxes: 12.53381° .. 12.53381° x 47.795° .. 47.795°
License: cc-by-nc-nd/4.0
Language: Deutsch
Time ranges: 1994-07-01 - 1997-09-30
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