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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and biological activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (1988)
    Springer
    Archives of toxicology 62 (1988), S. 359-368 
    Details
    ISSN: 1432-0738
    Keywords: 2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD ; Ethoxyresorufin O-deethylase ; Absorption ; Tissue distribution ; Pharmacokinetics ; Enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rat liver and adipose tissue, and hepatic ethoxyresorufin O-deethylase (EROD) activity were studied subsequent to a single subcutaneous injection of TCDD. Two types of experiments were performed to study: (a) time-dependent changes following a single injection of 300 ng TCDD/kg body wt (points 1–4), and (b) dose-dependent changes measurable after 7 days following a single injection (points 5–7). 1. Absorption of TCDD following a single subcutaneous injection was about 90% after 3 days and 98% after 5 days. 2. Following a single dose of 300 ng TCDD/kg body wt peak concentrations were: liver (after 3 days): 4.7±0.9 ng/g wet wt, and adipose tissue (after 7 days): 0.82±0.07 ng/g wet wt. 3. T1/2 of TCDD in liver was 13.6 days over the total experimental period (from day 10 to 91 of the study), apparently with an initial faster phase: 11.5 days (from day 10 to 49), and a slower period at the end of the experiment: 16.9 days (from day 49 to 91); in adipose tissue the t1/2 was 24.5 days (from day 14 to 91 of the study). 4. Maximum induction of EROD in the liver was observed (14-fold at 300 ng TCDD/kg body wt) 3–7 days following the injection; the activity was decreased to about one third of the maximum 3 weeks after the injection; increase in total cytochrome P-450 at this dose was only about 1.4-fold at the induction maximum. 5. The ratio of the TCDD concentrations in liver and adipose tissue increased considerably between doses of 3 ng TCDD/kg body wt (ratio∶about 0.74) and 3000 ng TCDD/kg body wt (ratio∶about 7.7). 6. The extent of EROD induction in the liver increased dose dependently. A significant effect was first observed with a dose of 3 ng TCDD/kg body wt (activity about +32% above control activity). The corresponding tissue concentration was about 10 pg TCDD/g liver wet wt. 7. An almost perfect linear relationship exists (when using a double-log plot) between the hepatic TCDD concentration and the EROD activity for tissue concentrations ranging from 40 to 30 000 pg TCDD/g wet wt.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00293624
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  • 2
    Electronic Resource
    Electronic Resource
    Absorption and tissue distribution of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in the rat (1989)
    Springer
    Archives of toxicology 63 (1989), S. 193-202 
    Details
    ISSN: 1432-0738
    Keywords: Absorption ; Tissue distribution ; Polychlorinated dibenzo-p-dioxins (PCDDs) ; Polychlorinated dibenzofurans (PCDFs)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A defined mixture of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) was parenterally administered to rats and absorption and tissue distribution were measured: 1) Toluene/DMSO (1+2; v/v) proved to be a convenient vehicle for the subcutaneous administration of the various PCDDs and PCDFs. Seven days after application the rate of absorption was 90% of the administered dose or even higher for almost all of the PCDDs/PCDFs in the mixture. In a few cases only (e.g. OCDD) the rate was found to be 84–89%; 2) Seven days after subcutaneous administration all 2378-substituted congeners were found in the liver, whereas only a few non-2378-substituted congeners could be measured in minor quantities. The 2378-substituted congeners also predominated in adipose tissue; however, most of the non-2378-substituted congeners were also detected; 3) The amount deposited within the liver as percentage of the administered dose differed for the various 2378-substituted PCDDs and PCDFs, ranging from 〈10% for OCDD or 2378-T4CDF, and between 60 and close to 100% for 12378-P5CDD or the H6CDDs. Therefore, the concentration ratio (liver/adipose tissue) was also found to be very different, ranging from 〈3 in the case of 2378-T4CDD or 2378-T4CDF to 〉40 in the case of 1234678-H7CDD, 23478-P5CDF, 123678-H6CDF, or 1234678-H7CDF; 4) Studies performed at the time period of ongoing absorption (13–14 h after injection) provided the first evidence that some of the non-2378-substituted congeners do reach substantial concentrations in hepatic tissue shortly after administration; 5) Subsequent to intraperitoneàl injection of the same PCDD/PCDF mixture the concentrations within the liver were found to be almost identical with that found after subcutaneous injection. In contrast, much higher concentrations of the congeners were found in (abdominal) adipose tissue; 6) In the liver of untreated rats of the same strain no T4CDDs/T4CDFs
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316368
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  • 3
    Electronic Resource
    Electronic Resource
    Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys (1990)
    Springer
    Archives of toxicology 64 (1990), S. 431-442 
    Details
    ISSN: 1432-0738
    Keywords: Tissue distribution ; Toxicokinetics ; Elimination ; Half-life ; Polychlorinated dibenzo-p-dioxins (PCDDs) ; Polychlorinated dibenzofurans (PCDFs) ; Marmoset monkeys (Callithrix jacchus)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A defined mixture of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) was subcutaneously administered to marmoset monkeys (Callithrix jacchus). Tissue concentrations in hepatic and adipose tissue were measured at different times after treatment (1–28 weeks). One week after application high concentrations could be detected for the 2,3,7,8-substituted congeners only. The percent of the administered dose in whole liver differed for the various 2,3,7,8-substituted congeners, ranging from 24.5±4.5% for 2,3,7,8-TCDD to 74.1±4.9% for 2,3,4,6,7,8-H6CDF. Therefore, the concentration ratio (liver/adipose tissue) was also very different, ranging from about 1 (2,3,7,8-T4CDD or 2,3,7,8-T4CDF) to 〉10 in the case of some higher chlorinated PCDDs and PCDFs. Half-lives of PCDDs and PCDFs were very different for the various 2,3,7,8-substituted congeners. For the most toxic compound (2,3,7,8-T4CDD) a t/2 of about 8 weeks in hepatic tissue and about 11 weeks in adipose tissue was found when calculated from data obtained later than 6 weeks after injection. For 2,3,7,8-T4CDD and 1,2,3,7,8-P5CDD the decreases in hepatic concentrations were much faster during the first 6 weeks after administration (t/2 of 4 weeks). This was apparently due to redistribution phenomena. Half-life increased with increasing degrees of chlorination. In some cases (e.g. OCDD, OCDF) no significant decrease in tissue concentrations could be observed after 28 weeks. The shortest t/2 was determined for 2,3,7,8-T4CDF: shorter than 6 days in hepatic tissue and about 10 days in adipose tissue. Calculation of the body burden of thenon-2,3,7,8-substituted PCDDs/PCDFs 1 week after injection revealed that all groups of isomers were present at less than 5%. Consequences of these findings for the use of TCDD-toxic-equivalency factors are discussed and a change in strategy is suggested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01977624
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  • 4
    Electronic Resource
    Electronic Resource
    Elimination of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in rat faeces (1989)
    Springer
    Archives of toxicology 63 (1989), S. 75-78 
    Details
    ISSN: 1432-0738
    Keywords: Polychlorinated dibenzo-p-dioxins (PCDDs) ; Polychlorinated dibenzofurans (PCDFs) ; Elimination ; Faeces
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A defined mixture (of a composition characteristic of that present in incinerator fly ash) of polychlorinated dibenzo-p-dioxins and -furans (PCDDs and PCDFs) was subcutaneously administered to rats and the elimination of the unchanged congeners via faeces was measured. 1) All congeners administered could be found in faeces. 2) The rates of elimination via faeces were rather different for the different congeners. 3) The most toxic congeners, 2378-T4CDD and 12378-P5CDD, were present in unmetabolized form in faeces to 〈 4% and 〈 8% of the administered dose within the first week. Thus, parenteral administration clearly minimizes contamination of the animal quarters when compared with corresponding oral dosing. 4) The rate of unchanged elimination was apparently especially pronounced for the higher chlorinated PCDDs and PCDFs. The highest excretion rate was found for 1234678-H7CDD (up to 30% of administered dose). 5) No obvious differences were observed in the rates of elimination of the unchanged substances via faeces of the 2378-substituted or the non-2378-substituted isomers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00334639
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