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A critical comparison of murine pathology and epidemiological data of TCDD, PCB126, and PeCDF
Katsuhiko Yoshizawa1, Allison Heatherly, David E Malarkey
1Toxicologic Pathology, Drug Safety Research Laboratories, Astellas Pharma Inc., Yodogawa, Osaka, Japan.
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.
Insights
Dioxin-like compounds (DLCs) cause toxicities in humans and animals. This review compares human and rodent studies, finding consistent target organs like the liver and immune system affected by DLC exposure.
Area of Science:
- Environmental Toxicology
- Comparative Pathology
- Toxicology
Background:
- Dioxin-like compounds (DLCs) are environmental contaminants causing significant toxicities.
- Human exposure to DLCs, primarily through diet, necessitates understanding mixture toxicity.
- The Toxic Equivalency Factor (TEF) aids in assessing health risks from DLC mixtures.
Purpose of the Study:
- To review human pathological effects of specific DLCs: TCDD, PCB 126, and PeCDF.
- To compare human pathologies with findings from National Toxicology Program (NTP) rodent studies.
- To identify consistent target organs affected by DLCs in both humans and rodents.
Main Methods:
- Literature review of human case studies involving TCDD, PCB 126, and PeCDF exposure.
- Comparative analysis of human pathology data with NTP rodent toxicity and carcinogenicity study results.
- Identification and collation of common pathological findings and affected organ systems.
Main Results:
- Consistent target organs were identified in both human and rodent studies, including the liver, oral cavity, cardiovascular system, immune system, thyroid, pancreas, and lung.
- While specific pathologies varied, the overall pattern of organ susceptibility to DLCs showed significant overlap.
- NTP rodent studies provided valuable comparative data for understanding human health risks.
Conclusions:
- Human and rodent studies show remarkable consistency in target organs affected by dioxin-like compounds.
- Comparative pathology is crucial for extrapolating animal toxicity data to human risk assessment.
- Understanding DLC toxicity is vital for public health, especially concerning dietary exposure to mixtures.
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