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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 60 (1987), S. 77-80 
    ISSN: 1432-0738
    Schlagwort(e): n-Hexane ; Pharmacokinetics ; Man ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The pharmacokinetics of inhaled n-hexane in rat and man were compared. In the rat metabolism was saturable. Up to 300 ppm, the metabolic rate was directly proportional to the concentration in the atmosphere, reaching 47 μmol/(h· kg). Only 17% of n-hexane was exhaled unchanged. Above 300 ppm, the amount of n-hexane in the body rose with increasing atmospheric concentrations from 1.6 up to a limiting value of 9.6, which corresponded to the thermodynamic distribution coefficient of n-hexane between the organism and the atmosphere. Up to 3000 ppm, the rate of metabolism increased to 245 μmol/ (h· kg); only a slow further increase was found up to 7000 ppm (285μmol/(h· kg)). In man the steady-state concentrations of n-hexane were about 1 ppm. The metabolic clearance was 1321/h, and n-hexane accumulated to a factor of 2.3 in the organism. The thermodynamic distribution coefficient was calculated to be 12. Twenty per cent of n-hexane in the body was exhaled unchanged. At low concentrations the rate of metabolism of n-hexane is limited in both species by transport to the enzyme system. Under these conditions the rate of metabolism of n-hexane should not be influenced by xenobiotics which induce the n-hexane metabolizing enzyme system.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 61 (1987), S. 131-137 
    ISSN: 1432-0738
    Schlagwort(e): n-Hexane ; 2,5-Hexanedione ; 4,5-Dihydroxy-2-hexanone ; Biological monitoring
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Male Wistar rats were exposed ton-hexane concentrations between 50 and 3000 ppm for 8 h, and urinary excretion kinetics of then-hexane metabolites 1-hexanol, 2-hexanol, 3-hexanol, 2-hexanone, 2,5-hexanedione, and 4,5-dihydroxy-2-hexanone were assessed. The amounts of metabolites excreted were linearly dependent on then-hexane exposure concentration, up to an exposure of about 300 ppm. Above 300 ppm exposure the metabolite excretion indicated saturation kinetics in the metabolism ofn-hexane. In its quantity, the newly described 4,5-dihydroxy-2-hexanone was the second metabolite, its amount in the urine being about ten times higher than that of excreted 2,5-hexanedione. Using gas chromatography-mass spectrometry the occurrence of 4,5-dihydroxy-2-hexanone as ann-hexane metabolite in urine of man was confirmed after exposure of a male volunteer to a mean of 217 ppmn-hexane for 4 h (laboratory exposure). Twenty-six hours after starting this exposure the excretion of 4,5-dihydroxy-2-hexanone (as a result of then-hexane exposure) reached a level which was four times higher than the excretion of 2,5-hexanedione. The results in both rat and man indicate the relevance of 4,5-dihydroxy-2-hexanone as a metabolite ofn-hexane metabolism. Formation of this metabolite may be viewed as a route of detoxification.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    International archives of occupational and environmental health 57 (1986), S. 149-158 
    ISSN: 1432-1246
    Schlagwort(e): n-Hexane ; Urine ; 2-Hexanone ; 2-Hexanol ; 2,5-Hexanedione
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Male Wistar rats were exposed to 1000 ppm n-hexane, and the excreted urinary metabolites were analyzed by capillary gas chromatography-mass spectrometry (GC-MS). 1-Hexanol, 2-hexanol, 3-hexanol, 2-hexanone, 2,5-hexanedione, 2,5-dimethyltetrahydrofuran, 2,5-dimethyl2,3-dihydrofuran and γ-valerolactone were identified by their retention times and their mass spectra. Quantitative gas chromatographic analyses were performed using an FID. Experiments on the hydrolysis of conjugated n-hexane metabolites revealed that enzymatic hydrolysis (in addition to acid hydrolysis) was not required, as treatment with HCl hydrolyzed conjugates sensitive to acid as well as conjugates sensitive to β-glucuronidase. By incorporating acid hydrolysis only and by using C18-cartridges for sample extraction, a method was developed that allowed the determination of n-hexane metabolites with a sample preparation time of only 45 min. Assay precision was assessed by repeated analyses of the same urine sample. Coefficients of variation for the individual metabolites ranged from between 1.8 and 3.3.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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