Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys.
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 greater than 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 the non-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.
Neubert
D
D
Institut für Toxikologie and Embryopharmakologie, Freie Universität Berlin, Federal Republic of Germany.
Wiesmüller
T
T
Abraham
K
K
Krowke
R
R
Hagenmaier
H
H
D000042:Absorption; D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics* / Q000633:toxicity; D001822:Body Burden; D002143:Callitrichinae; D004147:Dioxins / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D007279:Injections, Subcutaneous; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D001572:Benzofurans; D004147:Dioxins