A critical comparison of murine pathology and epidemiological data of TCDD, PCB126, and PeCDF

Abstract

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and dioxin-like compounds (DLCs) induce numerous toxicities, including developmental, endocrine, immunological, and multi-organ carcinogenic, in animals and/or humans. Multiple studies completed by the National Toxicology Program (NTP) focused on the effects caused in Harlan Sprague-Dawley rats by specific DLCs, among them the prototypical dioxin, TCDD. Because humans are exposed daily to a combination of DLCs, primarily via ingestion of food, the Toxic Equivalency Factor (TEF) was developed in order to evaluate health hazards caused by these mixtures. Herein we review the pathological effects reported in humans exposed to TCDD; 3,3',4,4',5-pentachlorobiphenyl (PCB 126); and 2,3,4,7,8,-pentachlorodibenzofuran (PeCDF) and compare them to similar changes seen in NTP murine studies performed with the same compounds. While there were differences in specific pathologies observed, clear consistency in the target organs affected (liver, oral cavity, cardiovascular system, immune system, thyroid, pancreas, and lung) could be seen in both human studies and rodent toxicity and carcinogenicity investigations.