SUBCHRONIC (13-WEEK) TOXICITY OF HEPTACHLORODIBENZO-P-DIOXIN IN MALE SPRAGUE-DAWLEY RATS

A 13-week oral toxicity study with 1,2,3,4,6,7,8-heptachlorodibenzo-p- dioxin (HpCDD) was performed in Sprague-Dawley rats. Rats received HpC DD at five different dose levels or 2,3,7,8-tetrachlorodibenzo-p-dioxi n (TCDD) at one dose level. The doses were divided into 4 daily loadin g doses and 6 biweekly maintenance doses. At the end of the 13-week do sing period half of the rats were scheduled for necropsy and the other half after another 13-week off-dose period. This preliminary report c ontains only data from male rats during the 13-week main study period. At the two highest doses of HpCDD and in the TCDD dosage group the bo dy weight or body weight gain was reduced. Mortality was 15, 50 and 5% , respectively. Wasting syndrome was the primary cause of death, but s ome rats died of hemorrhage without wasting, which may be related to t he dose-dependent decrease in platelet counts. Phosphoenolpyruvate car boxykinase (PEPCK), the rate limiting enzyme of gluconeogenesis, was d ecreased only at the two highest dose levels of HpCDD and in the TCDD group, all of which also showed mortality. Ethoxyresorufin O-deetylase (EROD) was induced dose-dependently in all treated groups. Serum tota l thyroxine (T4) concentrations were decreased beginning at the middle dose of HpCDD. The study demonstrates that the toxicity observed afte r subchronic exposure to HpCDD is very similar to that of TCDD. Most i mportantly, most of the effects after subchronic and acute dose exposu re are identical, confirming the validity of 0.007 as the toxic equiva lency factor for HpCDD.