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  • 1
    Electronic Resource
    Electronic Resource
    Phthalate esters (1984)
    Springer
    Archives of toxicology 55 (1984), S. 132-136 
    Details
    ISSN: 1432-0738
    Keywords: Phthalate esters ; Inhalation ; Rat ; Enzymatic activities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Sprague Dawley rats were exposed to dibutylphthalate (DBP) by inhalation with concentrations of 0.5, 2.5, and 7.0 ppm in the air for 5 days. The concentrations were considered relevant to human exposure. No quantitative changes were observed in liver microsomal cytochrome P-450 related enzymes, but significant increase was observed in the liver microsomal metabolism of benzo(a)pyrene and n-hexane, in the 2.5 ppm and 0.5 ppm groups, respectively. Inhaled DBF decreased in a dose-dependent way the lung microsomal concentration of cytochrome P-450 by as much as 63%, which was reflected in a significant reduction of the microsomal metabolism of n-hexane and benzo(a)pyrene in the 7.0 ppm group. It is concluded that DBP in doses relevant to human air exposure influences the cytochrome P-450 enzyme system in both liver and lung, with lung as the main target organ. The observed effects in lung microsomes were similar to those earlier reported after IP administration of high doses of DBP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00346052
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Phthalate esters I: effects on cytochrome P-450 mediated metabolism in rat liver and lung, serum enzymatic activities and serum protein levels (1982)
    Springer
    Archives of toxicology 50 (1982), S. 1-10 
    Details
    ISSN: 1432-0738
    Keywords: Phthalate esters ; Liver ; Lung ; Blood ; Rat ; Enzymatic activities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dimethylphthalate (DMP), dibutylphthalate (DBP) and di(2-ethylhexyl)phthalate (DEHP) were given i.p. (3.8 mM/kg) to Sprague Dawley rats for 5 days. DBP increased significantly the liver concentration of cytochrome P-450, but decreased the lung concentration by about 40%. DBP decreased the lung concentration of cytochrome b5 and NADPH-cytochrome-c-reductase activity by about 30%. Only minor effects were seen after treatment with DMP and DEHP. The direction of B(a)P metabolism was changed and the formation of 2- and 3-hexanol metabolites were increased in liver microsomes after DBP treatment. All phthalate esters decreased the lung metabolism of B(a)P. The cytochrome P-450 enzyme system in the lung was ten times more effective than that in the liver as far as metabolism of n-hexane was concerned. Only minor effects were observed in serum enzyme activities, but a significant decrease in the serum level of albumin was observed after treatment with DBP. No relationship was found between the carbon chain length of the investigated chemicals and effects on microsomal enzymatic activities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00569231
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Single and repeated dose pharmacokinetics of thio-TEPA in patients treated for ovarian carcinoma (1987)
    Springer
    Cancer chemotherapy and pharmacology 19 (1987), S. 143-148 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Triethylenethiophosphoramide (thio-TEPA) pharmacokinetics were studied in 15 patients being treated for epithelial ovarian carcinoma. Unchanged thio-TEPA was assayed in serum and urine by means of a gas chromatographic procedure. No accumulation or alteration of the pharmacokinetics occurred during therapy, which was continued for up to 7 months with biweekly administrations of 20 mg, after two initial loading courses with 20 mg daily for 3 consecutive days 2 weeks apart. No significant difference in the pharmacokinetics between i. m. and i. v. administration was demonstrated. However, three patients showed a reduced absorption ability from the i. m. injection site to the systemic circulation and an apparent increase in the elemination half-life (3.86±0.97 h), which could be of clinical relevance. A first-order elimination process with a short elimination half-life (∼1.5 h) was demonstrated for thio-TEPA in all patients after i.v. administration. The apparent volume of distribution averaged 50 1. The renal clearance was below 1% of the total-body clearance, which averaged 412 ml/min. The urinary excretion of unchanged thio-TEPA was complete within 8 h after administration, with an average urinary recovery of 0.14% of the dose. Calculation of the area under the serum concentration vs time curve revealed wide variation between patients (range 517–1480 ng/h ml-1), indicating the need for drug monitoring during therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00254567
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    Paper (German National Licenses)
    Fulltext
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