PuSH - Publication Server of Helmholtz Zentrum München: Comparative Toxicity of Four Chlorinated Dibenzo-p-dioxins (CDDs) and their Mixture. Part III: Structure-activity Relationship with Increased Plasma Tryptophan Levels, but no Relationship to Hepatic Ethoxyresorufin o-deethylase Activity.

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Weber, L.W.D. ; Lebofsky, M. ; Stahl, B.U. ; Kettrup, A. ; Rozman, K.K.

Comparative Toxicity of Four Chlorinated Dibenzo-p-dioxins (CDDs) and their Mixture. Part III: Structure-activity Relationship with Increased Plasma Tryptophan Levels, but no Relationship to Hepatic Ethoxyresorufin o-deethylase Activity.

Arch. Toxicol. 66, 484-488 (1992)

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Male Sprague-Dawley rats were treated with an LD20, an LD50, and an LD80 of 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), 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDD), respectively, and a mixture of the four homologues where each CDD was represented at one-fourth its previously established LD20, LD50, and LD80, respectively. Plasma tryptophan levels, liver ethoxyresorufin O-deethylase (EROD) activities, and liver weights were determined at 2 and 8 days after treatment. Plasma tryptophan levels were dose-dependently elevated, particularly at 8 days after treatment, by as much as 75% over control levels. EROD activity in CDD-treated animals was induced 27- to 28-fold, as compared with vehicle-treated controls, but did not show any dose-response. Liver weights were also significantly increased by the CDD treatments, but the increase was not dose related. There was no correlation between plasma tryptophan levels, a biomarker of acute toxicity of CDDs, and EROD activity, a biomarker of arylhydrocarbon (Ah) receptor-mediated enzyme induction. It is concluded that the acute toxicity of CDDs, which correlates and shows perfect structure-activity relationship with reduced activities of key enzymes of intermediary metabolism, and the induction of enzymes by much lower doses of CDDs in the liver, have different mechanisms of action.

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