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  • Articles: DFG German National Licenses  (3)
  • Inhalation  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Inhalation pharmacokinetics based on gas uptake studies (1984)
    Springer
    Archives of toxicology 55 (1984), S. 213-218 
    Details
    ISSN: 1432-0738
    Keywords: Ethylene ; 1,3-Butadiene ; Inhalation ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of ethylene and 1,3-butadiene were studied in male Sprague-Dawley rats by use of a closed inhalation chamber system. Both compounds showed saturable metabolism when untreated rats were used. “Linear” pharmacokinetics applied at exposure concentrations below 800 ppm ethylene and below 1,000 ppm 1,3-butadiene. A constant elimination rate, indicative of metabolic saturation, occurred at concentrations higher than 1,000 ppm ethylene or 1,500 ppm 1,3-butadiene. Pretreatment with aroclor 1254 (polychlorinated biphenyls) increased V max for both compounds. For 1,3-butadiene, no saturation of metabolic capacity was observed with exposure concentrations up to 12,000 ppm when the rats were pretreated with aroclor 1254. A comparison with previous studies on ethane and n-pentane suggested that introduction of a double bond into a saturated aliphatic hydrocarbon increased the rate of metabolism under conditions in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00341013
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Species differences in butadiene metabolism between mice and rats evaluated by inhalation pharmacokinetics (1986)
    Springer
    Archives of toxicology 58 (1986), S. 235-238 
    Details
    ISSN: 1432-0738
    Keywords: 1,3-Butadiene ; Inhalation ; Pharmacokinetics ; Species differences ; Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Metabolism of 1,3-butadiene to 1,2-epoxybutene-3 in rats follows saturation kinetics. Comparative investigation of inhalation pharmacokinetics in mice also revealed a saturation pattern. For both species “linear” pharmacokinetics apply at exposure concentrations below 1000 ppm 1,3-butadiene; saturation of butadiene metabolism is observed at atmospheric concentrations of about 2000 ppm. For mice metabolic clearance per kg body weight in the lower concentration range where first order metabolism applies was 7300ml×h−1 (rat: 4500 ml×h−1). Maximal metabolic elimination rate (Vmax) was 400 μmol×h−1 ×kg−1 (rat: 220 μmol ×h−1×kg−1). This shows that 1,3-butadiene is metabolized by mice at higher rates compared to rats. Based on these investigations, the metabolic elimination rates of butadiene in both species were calculated for the exposure concentrations applied in two inhalation bioassays with rats and with mice. The results show that the higher rate of butadiene metabolism in mice when compared to rats may only in part be responsible for the considerable difference in the susceptibility of both species to butadiene-induced carcinogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00297112
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Inhalation pharmacokinetics of 1,2-epoxybutene-3 reveal species differences between rats and mice sensitive to butadiene-induced carcinogenesis (1987)
    Springer
    Archives of toxicology 61 (1987), S. 7-11 
    Details
    ISSN: 1432-0738
    Keywords: Butadiene ; Epoxybutene ; Inhalation ; Species differences ; Metabolism ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Comparative investigations of inhalation pharmacokinetics of 1,2-epoxybutene-3 (vinyl oxirane, the primary reactive intermediate of butadiene) revealed major differences in metabolism of this compound between rats and mice. Whereas in rats no indication of saturation kinetics of epoxybutene metabolism could be observed up to exposure concentrations of 5000 ppm, in mice saturation of epoxybutene metabolism becomes apparent at atmospheric concentrations of about 500 ppm. The estimated maximal metabolic rate (Vmax) in mice for epoxybutene was only 350 μmol×h−1×kg−1 (rats: 〉2600 μmol× h−1×kg−1). In the lower concentration range where first order metabolism applies (up to about 500 ppm) epoxybutene is metabolized by mice at higher rates compared to rats (metabolic clearance per kg body weight, mice: 24900 ml×h−1, rats: 13400 ml×h−1). Under these conditions the steady state concentration of epoxybutene in the mouse is about 10 times that in the rat. When mice are exposed to high concentrations of butadiene (〉2000 ppm; conditions of saturation of butadiene metabolism; closed exposure system) epoxybutene is exhaled by the animals, and its concentration in the gas phase increases with exposure time. At about 10 ppm epoxybutene signs of acute toxicity are observed. When rats are exposed to butadiene under similar conditions, the epoxybutene concentration reaches a plateau at about 4 ppm. Under these conditions hepatic non-protein sulfhydryl compounds are virtually depleted in mice but not in rats. We conclude that in addition to the higher rate of metabolism of butadiene in mice, limited detoxification and consequently accumulation of its primary reactive intermediate epoxybutene may be a major determinant for the higher susceptibility of mice to butadiene-induced carcinogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00324541
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    Paper (German National Licenses)
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