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Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture

Part I: Acute toxicity and toxic equivalency factors (TEFs)

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Abstract

There is presently no scientifically proven method to assess the toxicity of environmental samples containing complex mixtures of chlorinated dibenzo-p-dioxins (CDDs) of known composition. Their risk assessment is currently based on the interim concept of toxicity equivalency factors (TEFs), with the unproven assumption that all interactions of CDDs are additive. To address this problem we conducted acute toxicity studies with four different CDDs, viz 2,3,7,8-tetrachlorodibenzo-p-dioxin (tetra-CDD), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (penta-CDD), 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (hexa-CDD) and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDD), all containing chlorine substituents in the crucial 2,3,7,8-positions. The homologues, dissolved in corn oil/acetone, were administered to groups of five male Sprague Dawley rats at several doses (at least three) by gastric intubation. The obtained mortality data were employed to calculate the LD20,50 and80 for each homologue. These data were subsequently used to prepare equipotent doses (expected mortality of 20, 50 and 80%) of a mixture containing all four homologues, each of them contributing one fourth of the toxicity, under the assumption of additive toxicity. The obtained LD50 value and (TEF) was for tetra-CDD 43 μg/kg (1), penta-CDD 206 μg/kg (0.2) hexa-CDD 887 μg/kg (0.05) and hepta-CDD 6325 μg/kg (0.007), respectively. The dose-response to the mixture confirmed the hypothesis of strict additivity in the acute toxicity of the four CDD homologues.

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Authors and Affiliations

  1. Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 39th and Rainbow Boulevard, 66 160-7717, Kansas City, KS, USA

    Bernhard U. Stahl & Karl Rozman

  2. Section of Environmental Toxicology, GSF - Institut für Toxikologie, W-8042, Neuherberg, Federal Republic of Germany

    Bernhard U. Stahl & Karl Rozman

  3. GSF - Institut für Ökologische Chemie, W-8042, Neuherberg, Federal Republic of Germany

    Antonius Kettrup

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  1. Bernhard U. Stahl
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  2. Antonius Kettrup
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  3. Karl Rozman
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Stahl, B.U., Kettrup, A. & Rozman, K. Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. Arch Toxicol 66, 471–477 (1992). https://doi.org/10.1007/BF01970671

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  • DOI: https://doi.org/10.1007/BF01970671

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