Absorption and tissue distribution of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in the rat.
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 less than 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 less than 3 in the case of 2378-T4CDD or 2378-T4CDF to greater than 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 intraperitoneal 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 or P5CDDs/P5CDFs were detectable under our experimental conditions.
Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Federal Republic of Germany.
K
K
Abraham
T
T
Wiesmüller
H
H
Brunner
R
R
Krowke
H
H
Hagenmaier
D
D
Neubert
D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics*; D004147:Dioxins / Q000493:pharmacokinetics*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007408:Intestinal Absorption; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D001572:Benzofurans; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins