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Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys

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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.

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Abbreviations

PCDDs/PCDFs:

polychlorinated dibenzo-p-dioxins and dibenzofurans

T4CDDs/T4CDFs:

tetra-chlorinated dibenzo-p-dioxins and dibenzofurans

P5CDDs/P5CDFs:

penta-chlorinated dibenzo-p-dioxins and dibenzofurans

H6CDDs/H6CDFs:

hexa-chlorinated dibenzo-p-dioxins and dibenzofurans

H7CDDs/H7CDFs:

hepta-chlorinated dibenzo-p-dioxins and dibenzofurans

OCDD/OCDF:

octa-chlorinated dibenzo-p-dioxin and dibenzofuran

DMSO:

dimethylsulfoxide

TE-factor:

Toxic equivalency factor, used for risk assessment, is assumed to compare the toxicity of the congener with that of 2,3,7,8-T4CDD (toxicity = 1)

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Authors and Affiliations

  1. Institut für Toxikologie and Embryopharmakologie, Freie Universität Berlin, Garystrasse 5, D-1000, Berlin 33, Federal Republic of Germany

    Diether Neubert, Klaus Abraham & Ralf Krowke

  2. Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, D-7400, Tübingen, Federal Republic of Germany

    Thomas Wiesmüller & Hanspaul Hagenmaier

Authors
  1. Diether Neubert
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  2. Thomas Wiesmüller
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  3. Klaus Abraham
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  4. Ralf Krowke
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  5. Hanspaul Hagenmaier
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Additional information

Data presented in this paper are part of the doctoral thesis of Thomas Wiesmüller submitted to the Fakultät für Chemie und Pharmazie, Eberhard-Karls-Universität, Tübingen

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Neubert, D., Wiesmüller, T., Abraham, K. et al. Persistence of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in hepatic and adipose tissue of marmoset monkeys. Arch Toxicol 64, 431–442 (1990). https://doi.org/10.1007/BF01977624

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  • DOI: https://doi.org/10.1007/BF01977624

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