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Origin and Distribution of Potassium Bromate-Induced Testicular and Peritoneal Mesotheliomas in Rats

US Environmental Protection Agency and Department of Toxicology, North Carolina State University, Research Triangle Park, North Carolina 27711,

Kevin T. Morgan

GlaxoWellcome Inc, 5 Moore Drive, Research Triangle Park, North Carolina 27709, lmc78819{at}glaxowellcome.com

Betty Gaskill

GlaxoWellcome Inc, 5 Moore Drive, Research Triangle Park, North Carolina 27709

D.C. Wolf

US Environmental Protection Agency, TW Alexander Drive, Research Triangle Park, North Carolina 27711

A.B. Deangelo

US Environmental Protection Agency, TW Alexander Drive, Research Triangle Park, North Carolina 27711

Tissue sections were examined from a 2-year bioassay of male Fischer 344 rats treated with potassium bromate administered in drinking water. All animals exhibiting peritoneal mesotheliomas also had mesotheliomas of the tunica vaginalis testis mesorchium (the reverse was not true), and the correlation of these 2 types of mesotheliomas was highly significant (r2 = 0.98). Mapping of the tunica vaginalis tumors at all time points and at all bromate concentrations revealed a pattern of increasing incidence of tumor formation on the mesothelium of the tunica vaginalis testis as a function of proximity to the mesorchial ligament. Thus, the mesorchium appears to be the major mesothelial target site for potassium bromate-mediated carcinogenesis. The frequency of occurrence of mesotheliomas by location was tunica vaginalis testis (25%), mesosplenium (20%), mesentery (10%), mesojejunum/mesocolon (8%), bladder (6.5%), mesogastrium (13%), liver serosa (5%), and kidney, small intestine, and rectum (1% each). A complete cross-section of the rat testis was prepared and used to construct a complete map of the mesothelium. Any attempt to determine the role of local dose and tissue susceptibility for the purpose of interspecies risk extrapolation must take into account the complex anatomy and physiology of this region of the visceral and testicular suspensory apparatus. Improved histologic approaches are needed for adequate assessment of this delicate suspensory system.

Key Words: Rat testis • tunica vaginalis • water disinfection byproducts • mesorchium • carcinogenesis • risk assessment

Toxicologic Pathology, Vol. 28, No. 2, 253-266 (2000)
DOI: 10.1177/019262330002800205


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