Porphyrogenic effect of chronic treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin in female rats. Dose-effect relationship following urinary excretion of porphyrins

The porphyrogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was evaluated in female rats treated chronically for 45 weeks with 0.01, 0.10, and 1.00 μg/kg TCDD per week. The time course of the urinary porphyrin pattern was followed in order to determine the qualitative and quantitative composition in urine and to test the sensitivity of a parameter such as porphyrins in urine as an indication of exposure to TCDD. The results showed that the dose of 0.01 μg/kg/week resulted in significantly enhanced excretion of coproporphyrin from 6 months onward; with the dose of 0.10 μg/kg/week coproporphyrinuria was observed after 3 months and was associated at 10 months with a significant rise in uroporphyrin. The highest dose (1.00 μg/kg/week) caused enhanced excretion of coproporphyrin from 2 months onward. This effect was associated, at 6 months, with an increase in heptacarboxylic porphyrin and uroporphyrin excretion. A marked porphyric state was established in this group of animals from 8 months onward as indicated by massive enhancement of total urinary porphyrin excretion (about 70 times higher than the control group) with a large prevalence of porphyrins with a high number of carboxyl groups and reversal of the coproporphyrin/uroporphyrin ratio. Accumulation of porphyrins was also observed in liver, spleen, and kidneys of this group of animals. Terminal livers of rats treated with 0.01, 0.10, and 1.00 μg/kg/week contained 1050, 4740, and 30,700 ppt, respectively. Comparison of our data with the literature on the porphyrogenic effect of hexachlorobenzene indicated that TCDD can be considered 1400 times more potent.