INCREASED COPPER CONCENTRATIONS IN RAT-TISSUES AFTER ACUTE INTOXICATION WITH 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN

Recently, acutely toxic doses of the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been reported to affect the hepatic distribution of essential metals in the rat. However, the reduced food intake by TCDD was not taken into account. Therefore, metal concentrations were determined in different rat tissues at the end of a toxicity study with TCDD in which a pair-fed control group was introduced. Male Sprague-Dawley rats received a single i. p. injection of corn oil/acetone with or without TCDD at 125-mu-g/kg. Controls and TCDD-treated rats were fed ad libitum; additionally, pair-fed controls received the amount of food consumed by their TCDD-treated partners 1 day before. Twenty-one days after dosing rats were killed and samples of liver, kidney and jejunum were taken for the analysis of Ca, Cu, Fe, Mg, Mn, and Zn. After acid digestion of the tissues metals were determined by atomic emission spectrometry (AES). The most outstanding effect of TCDD treatment was an increase of the copper levels in the kidney (4-fold, versus pair-fed controls) and in the liver (> 2-fold, versus pair-fed controls). Other metals were mainly affected by the reduced food intake only. Since Cu represents a trace metal the homeostasis of which depends on its biliary excretion and since TCDD is known to impair biliary flow and excretion, an impaired biliary excretion of Cu by TCDD is suggested as the causal mechanism.