Toxicologic Pathology

 

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Toxicologic Pathology, Vol. 35, No. 7, 865-879 (2007)
DOI: 10.1080/01926230701618516

Invited Review

A Critical Comparison of Murine Pathology and Epidemiological Data of TCDD, PCB126, and PeCDF

Katsuhiko Yoshizawa1,2, Allison Heatherly3, David E. Malarkey3, Nigel J. Walker4 and Abraham Nyska

1 Toxicologic Pathology, Drug Safety Research Laboratories, Astellas Pharma Inc., Yodogawa, Osaka 532-8514, Japan
2 Pathology II, Kansai Medical University, Moriguch, Osaka 570-8506, Japan
3 Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, USA
4 Environmental Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, USA
5 Toxicologic Pathologist, Timrat 23840, Israel

Correspondence: Address correspondence to Abraham Nyska, Toxicological Pathologist, Haharuv 18, P.O. Box 184, Timrat, 23840, Israel. E-mail:anyska{at}bezeqint.net

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.

Key Words: Carcinogenesis • dioxin • human • PCB126 • PeCDF • rodent • TCDD

Abbreviations: AhR, aryl hydrocarbon receptor • ATSDR, Agency for Toxic Substances and Disease Registry • CYP, cytochrome P450 • DLC, dioxin-like compound • IARC, International Agency for Research on Cancer • NTP, National Toxicology Program • PCB 126, 3, 3', 4, 4'5-pentachlorobiphenyl • PCDD, polychlorinated dibenzodioxin • PCDF, polychlorinated dibenzofuran • PeCDF, 2, 3, 4, 7, 8-pentachlorodibenzofuran • TCDD, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin • TBG, thyroxine-binding globulin • UGT, UDP-glucuronosyltransferases


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