HISTOPATHOLOGY OF INTERSCAPULAR BROWN ADIPOSE-TISSUE, THYROID, AND PANCREAS IN 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN (TCDD)-TREATED RATS

The time course of histological changes was studied in rats lethally intoxicated (150 .mu.g/kg) with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In addition to TCDD-caused tissue damage described by others, the thyroid, pancreas, and interscapular brown adipose tissue (IBAT) were identified as tissues affected by TCDD. Because histological changes in the thyroid and pancreas occurred late (7 days after dosing), these effects are viewed as secondary due to altered hormonal homeostases. Both light and electron microscopic examination of IBAT identified this tissue as a target in TCDD toxicity. Histological changes in IBAT are characterized by three phases: (1) "fatty" IBAT (Days 1 to 3 after dosing); (2) fat depletion accompanied by glycogen accumulation (Days 4 to 7 after dosing); and (3) complete fat and glycogen depletion together with massive cellular damage (Days 8 to 14), particularly affecting the mitochondria. It is concluded that brown adipose tissue is a primary target in TCDD toxicity. It seems that destruction of brown adipose tissue by TCDD leads to an energy imbalance resulting in reduced oxygen consumption which forces animals to contribute a greater proportion of energy to the maintenance of their body temperature by anaerobic pathways. It is suggested that this less efficient energy utilization is the cause of a wasting syndrome.