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Olfactory Epithelial Metaplasia and Hyperplasia in Female Harlan Sprague–Dawley Rats Following Chronic Treatment with Polychlorinated Biphenyls
1 Laboratory of Experimental Pathology Correspondence: Address correspondence to: Dr. Abraham Nyska, Laboratory of Experimental Pathology, MD B3-06, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709-9998, USA; e-mail:nyska{at}niehs.nih.gov
The National Toxicology Program recently completed a series of studies to evaluate the relative potency for toxicity and carcinogenicity of several polyhalogenated aromatic hydrocarbons including dioxin-like compounds (DLCs) and polychlorinated biphenyls. Female Sprague–Dawley rats were administered by gavage for up to 2 years with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); 3,3',4,4',5-pentachlorobiphenyl (PCB126); 2,3,4,7,8-pentachlorodibenzofuran (PeCDF); 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153); a tertiary mixture of TCDD, PCB126, and PeCDF; a binary mixture of PCB126 and 153; or a binary mixture of PCB126 and 2,3',4,4',5-pentachlorobiphenyl (PCB118); control animals received corn oil-acetone vehicle (99:1) alone. Nasal epithelial changes were observed only in animals exposed for 2 years to the higher doses of the binary mixtures of PCB126 + PCB153 (1000 ng/kg and 1000 ug/kg) and PCB126 + PCB118 (216 and 360 ng TCDD equivalents/kg). In both studies, the changes were of the same nonneoplastic nature, localized to nasal sections II and III located, respectively, at the level of the incisive papilla anterior to the first palatial ridge (section II) and through the middle of the second molar teeth (section III). The changes consisted of hyperplasia of the respiratory epithelium (level II) and metaplasia of olfactory epithelium to respiratory epithelium with further hyperplasia of the metaplastic respiratory epithelium (levels II and III). Variable amounts of acute inflammatory exudate appeared within the lumen of the nasal cavity, overlying the affected epithelium. Occasionally, the inflammation eroded through the skull and into the adjacent olfactory bulbs.
Key Words: Dioxin • furans • polychlorinated biphenyls • nasal cavity • olfactory epithelium • metaplasia • hyperplasia • toxic equivalency factor Abbreviations: AhR, aromatic hydrocarbon receptor • DLC, dioxin-like compound • H&E, hematoxylin and eosin • NTP, National Toxicology Program • PBDE, polybrominated diphenyl ether • PCB126, 3,3',4,4',5-pentachlorobiphenyl • PCDD, polychlorinated dibenzodioxin • PCDF, poly-chlorinated dibenzofuran • PCN, polychlorinated naphthalene • PeCDF, 2,3,4,7,8-pentachlorodibenzofuran • PHAH, polyhalogenated aromatic hydrocarbon • PWG, Pathology Working Group • QA, Quality Assurance • TEF, Toxic Equivalency Factor • TEQ, TCDD Toxic Equivalents • WHO, World Health Organization
Toxicologic Pathology, Vol. 33, No. 3,
371-377 (2005) This article has been cited by other articles:
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