SUBCHRONIC TOXICITY OF 2,3,7,8-TETRABROMODIBENZO-P-DIOXIN IN RATS

2,3,7,8-Tetrabromodibenzo-p-dioxin (2,3,7,8-TBDD) was administered dai ly to male and female rats for 91 days by gavage. Ten male and 10 fema le rats per group received 0.01, 0.1, 1, 3, or 10 pg 2,3,7,8-TBDD/kg b ody weight per dose per day, solubilised in arachis oil. At 1 mu g/kg per day and above, body weight gain was dose-dependently reduced by tr eatment. Animals in the 3 and 10 pg/kg dose groups showed symptoms of wasting syndrome. Fifty per cent of the animals in the 3 mu g/kg dose- group died and all animals of the highest dose (10 mu g/kg) died or ha d to be killed in extremis. Hematological investigations indicated cha nges -mainly in the 1 and 3 mu g/kg dose-groups-in hemoglobin content, packed cell volume and number of thrombocytes. The prothrombin-time w as markedly prolonged after 3 mu g/kg in week 13. Clinical chemistry p erformed at the end of treatment revealed an increase in plasma alkali ne phosphatase (APh), aspartate aminotransferase, ASAT and alanine ami notransferase, ALAT (females only) in the highest surviving dose-group (3 mu g/kg). Marginal changes of APh and ASAT were seen in rats in th e 1 mu g/kg dose-group. In the same animals, total bilirubin was eleva ted. Triglycerides were reduced mainly at 1 and 3 mu g/kg. Serum thyro xin was reduced, beginning with a marginal change at 0.1 mu g/kg, trii odothyronine was elevated, starting with a dose of 1 mu g/kg, Thymus w eights were reduced in rats of the 1, 3 and 10 mu g/kg dose-groups. Hi stopathological analysis showed atrophy of the lymphatic tissue in thy mus and spleen. Investigations of the liver indicated peliosis hepatis after treatment with 3 or 10 mu g/kg. Activities of microsomal enzyme s (ethoxyresorufin O-deethylase, ethoxycoumarin O-deethylase, aryl hyd rocarbon hydroxylase, UDP-glucuronyltransferase) investigated in liver , lung and kidney were dose-dependently elevated after 13 weeks of tre atment. At a dose of 3.0 mu g/kg, activities were below those of the d ose 1.0 mu g/kg, probably due to liver toxicity. The induction ratio o f kidney was generally higher than in liver and lung. No signs of trea tment-related toxicity were observed in the 0.01 and 0.1 mu g/kg group s after the subchronic administration of 2,3,7,8-TBDD by gavage.