Acute toxicity, inductive effects of liver enzymes and distribution in the liver of 1,2,3,7,8-pentachlorodibenzo-p-dioxin in rats

Acute toxicity, inductive effects of liver enzymes and liver persistency of 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PenCDD) were compared with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) using male Wistar rats. 1,2,3,7,8-PenCDD treatment at a dose of 0.1 mumol/kg resulted in significant depression of growth of rats from a day to 28 days after treatment. However, the effect was relatively less than that of 2,3,7,8-TCDD. On 5 days, similarly to 2,3,7,8-TCDD-treated group, liver hypertrophy and thymic atrophy were observed in 1,2,3,7,8-PenCDD-treated groups. In addition, 1,2,3,7,8-PenCDD showed potent 3-methylcholanthrene-type inducing ability. For example, the activities of benzo(a)pyrene 3-hydroxylase and DT-diaphorase were 25-fold and 10-fold of control, respectively. On 30 days, about 50% of the inductive effects on 5 days were maintained in both 1,2,3,7,8-PenCDD- and 2,3,7,8-TCDD-treated groups. Amount of 1,2,3,7,8-PenCDD distributed to the liver on 5 days was about 80-90% of dose and was about 1.5 times greater than that of 2,3,7,8-TCDD. About 50% of dose of 1,2,3,7,8-PenCDD remained even on 30 days after treatment. From these results, it is suggested that 1,2,3,7,8-PenCDD possessing the potent acute toxicity comparable to 2,3,7,8-TCDD and higher persistency in the liver might be more important than 2,3,7,8-TCDD in terms of the chronic toxicity.