TOXICOLOGIC STUDIES OF 2,3,7,8-TETRACHLORODIBENZO-p-DIOXIN (TCDD) IN RATS

Rats were maintained on diets supplying 0.1, 0.01 and 0.001 μg TCDD/kg/day, equivalent to 2200, 210 and 22 ppt of TCDD. Ingestion of 0.1 μg/kg/day caused multiple indications of toxicity, including decreased weight gain, increased mortality, slightly decreased erythroid parameters, increased urinary excretion of porphyrins and delta-aminolevulinic acid and abnormal liver function tests. Gross and histopathologic changes were noted in the hepatic, lymphoid, respiratory and vascular tissues. This high dose level caused an increased incidence of hepatocellular carcinomas and squamous cell carcinomas of the lung, hard palate/nasal turbinates or tongue, whereas a reduced incidence of tumors was noted in the pituitary, uterus, mammary gland, pancreas and adrenal. Terminal liver and fat samples from these rats given diets containing 2200 ppt of TCDD contained 24,000 and 8100 ppt of TCDD, respectively. Rats maintained on diets containing 0.01 μg/kg/day (210 ppt) had a lesser degree of toxicity, limited primarily to increased urinary excretion of porphyrin plus liver and lung lesions. Terminal liver and fat samples contained 5100 and 1700 ppt TCDD, respectively. Ingestion of 0.001 μg/kg/day (22 ppt in the diet) caused no effects considered to be of any toxicologic significance. Terminal liver and fat samples each contained 540 ppt of TCDD.