| Exocrine Pancreatic Pathology in Female Harlan Sprague-Dawley Rats after Chronic Treatment with 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Dioxin-like Compounds Abraham Nyska,1 Micheal P. Jokinen,2 Amy E. Brix,3 Donald M. Sells,4 Michael E. Wyde,5 Denise Orzech,5 Joseph K. Haseman,6 Gordon Flake,1 and Nigel J. Walker7 1Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA; 2Pathology Associates--A Charles River Company, Durham, North Carolina, USA; 3Experimental Pathology Laboratories, Research Triangle Park, North Carolina, USA; 4Battelle Columbus Laboratories, Columbus, Ohio, USA; 5Toxicology Operation Branch, 6Biostatistics Branch, and 7Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA Abstract
We evaluated the effect of chronic exposure to dioxin and dioxin-like compounds on the pancreas in female Harlan Sprague-Dawley rats. This investigation represents part of an ongoing National Toxicology Program initiative to determine the relative potency of chronic toxicity and carcinogenicity of polychlorinated dioxins, furans, and biphenyls. Animals were treated by gavage for up to 2 years with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) , 3,3´,4,4´,5-pentachlorobiphenyl (PCB-126) , 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) , or a toxic-equivalency-factor (TEF) mixture of these agents ; control animals received corn oil-acetone vehicle alone. A complete necropsy was performed on all animals, and a full complement of tissues was collected and examined microscopically. Administration of each of the four compounds was associated with increased incidences of several nonneoplastic changes in the exocrine pancreas, including cytoplasmic vacuolation, chronic active inflammation, atrophy, and arteritis. Low incidences, but higher than those in the historical database, of pancreatic acinar adenoma and carcinoma were seen in the TCDD, PeCDF, and TEF-mixture groups. These results indicate that the pancreatic acini are target tissues for dioxin and certain dioxin-like compounds. Key words: carcinogenesis, dioxin, furans, inflammation, pancreas, polychlorinated biphenyls. Environ Health Perspect 112:903-909 (2004) . doi:10.1289/ehp.6869 available via http://dx.doi.org/ [Online 4 March 2004]
Address correspondence to A. Nyska, Laboratory of Experimental Pathology, MD B3-06, NIEHS, P.O. Box 12233, Research Triangle Park, NC 27709 USA. Telephone: (919) 541-4282. Fax: (919) 541-7666. E-mail: nyska@niehs.nih.gov We thank J. Johnson, J. Dunnick, and R. Miller for their critical review of the manuscript ; M.H. Puccini and N. Flagler for expert preparation of the illustrations ; and J. Bucher, A. van Birgelen, D. Orzech, C. Smith, and M. Hejtmancik for their valued contributions to study design and conduct. The authors declare they have no competing financial interests. Received 19 November 2003 ; accepted 4 March 2004.
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