SUBCHRONIC CHRONIC TOXICITY OF 1,2,3,4,6,7,8-HEPTACHLORODIBENZO-P-DIOXIN (HPCDD) IN RATS .1. DESIGN, GENERAL OBSERVATIONS, HEMATOLOGY, AND LIVER CONCENTRATIONS/

Groups of 20 male and 20 female adult Sprague-Dawley rats were given f ive different doses of 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCD D). Total doses for males and females (30.9/18.5, 370/222, 2222/1333, 6667/4000, and 10000/6000 mu g/kg) were divided into four daily loadin g doses and six biweekly maintenance doses. Positive controls were adm inistered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, total dose 70/41. 9 mu g/kg). Liver concentrations, as determined by GC/MS, reflected qu ite accurately the calculated dose ratios. The dosing period was 13 we eks, after which half of the rats were necropsied and the rest provide d with an off-dose period of another 13 weeks. Body weight gain was do se-dependently reduced throughout the study. Mortality occurred dose-d ependently, starting on Day 22 and continuing until the end of the off -dose period. Mortality rates at the end of the off-dose period were 9 0 and 40% for males and 60 and 10% for females in the two highest dose groups. Clinical signs and necropsy findings suggested that the cause of death was related to wasting (early deaths), gastrointestinal and nasal hemorrhage (between Days 64 and 126), or anemia Gate deaths, aft er Day 111). Prothrombin times were prolonged intermittently, mainly a t the highest dose of HpCDD. Platelet counts were dose-dependently dec reased at the two highest doses of HpCDD and in the TCDD-treated group . This study demonstrates that the relative potency derived from acute toxicity studies is the same as that observed in this subchronic/chro nic toxicity study of HpCDD and TCDD, confirming the validity of 0.007 as the toxic equivalency factor (TEF) for HpCDD, which is in good agr eement with the international TEF Of 0.01. (C) 1997 Academic Press.