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

Lynn M. Crosby

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

References

  • Ahotupa M., Huhtaniemi I. (1992). Impaired detoxification of reactive oxygen and consequent oxidative stress in experimentally cryptorchid rat testis. Biol Reprod 46: 1114-1118.[Abstract]
  • Ballmaier D., Epe B. (1995). Oxidative DNA damage induced by potassium bromate under cell-free conditions and in mammalian cells. Carcinogenesis 16: 335-342.[Abstract/Free Full Text]
  • DeAngelo A., George M., Kilburn S., Moore T., Wolf D. ( 1998). Carcinogenicity of Potassium bromate administered in the drinking water to male B6C3F, mice and F344/N rats. Toxicol Pathol 26: 724-729.[Abstract/Free Full Text]
  • Dunnick J., Elwell M., Bucher J. (1994). Comparative toxicities of o-, m-, and p-nitrotoluene in 13-week feed studies in F344 rats and B6C3F1 mice. Fundam Appl Toxicol 22: 411-421.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Fisher N., Hutchinson J., Hardy J., Ginocchio A., Waite V. (1979). Long-term toxicity and carcinogenicity studies of the bread improver potassium bromate. 1. Studies in rats. Food Cosmet. Toxicol 17: 33-39.
  • Frandson RD, Spurgeon TL (1992). Anatomy and Physiology of Farm Animals, 5th ed. Lea & Febiger, Philadelphia.
  • Ginocchio A., Waite V., Hardy J., Fisher N., Hutchinson J., Berry R. (1979). Long-term toxicity and carcinogenicity studies of the bread improver potassium bromate. 2. Studies in mice. Food Cosmet Toxicol 17: 41-47.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Gould DH (1977). Mesotheliomas of the tunica vaginalis propria and peritoneum in Fischer rats. Vet Pathol 14: 372-379.[Abstract]
  • Greene EC (1963). Anatomy of the Rat. Hafner, New York.
  • Hijnen W., Voogt R., Veenendaal H., Jagt H., Kooij D. (1995). Bromate reduction by denitrifying bacteria. Appl Environ Microbiol 61: 239-244.[Abstract]
  • Ilgren EG (1993).Mesotheliomas of Animals; A Comprehensive, Tabular Compendium of the World's Literature. CRC Press, Oxford, England.
  • International Agency for Research on Cancer (1986). Some naturally occurring and synthetic food components, furocoumarins and ultraviolet radiation. IARC Monogr Eval Carcinog Risk Chem Hum 40: 207-220.[Medline] [Order article via Infotrieve]
  • Kurokawa Y., Maekawa A., Takahashi M., Hayashi Y. (1990). Toxicity and carcinogenicity of potassium bromate—A new renal carcinogen. Environ Health Perspect 87: 309-335.[Web of Science][Medline] [Order article via Infotrieve]
  • Maekawa A., Ogiu T., Matsuoka C., Onodera H., Furuta K., Kurokawa Y., Takahashi M., Kokubo T., Tanigawa H., Hayashi Y., Nakadate M., Tanimura A. (1984). Carcinogenicity of low doses of N-ethyl-N-nitrosourea in F344 rats: A dose-response study. GANN 75: 117-125.[Web of Science][Medline] [Order article via Infotrieve]
  • Mossman BT, Spivack S. (1994). Regulation of antioxidant enzymes in lung after oxidant injury. Environ Health Perspect 102: 79-87.
  • Nickel RS, Seiferle E., Sack WO ( 1973). The Viscera of the Domestic Mammals. Springer-Verlag, New York.
  • Sai K., Uchiyama S., Ohno Y., Hasegawa R., Kurokawa Y. (1992). Generation of active oxygen species in vitro by the interaction of potassium bromate with rat kidney cell. Carcinogenesis 13: 333-339.[Abstract/Free Full Text]
  • Sai KT, Thomas DW, Dabbs JE, Hasegawa R., Kurokawa Y. (1994). Oxidative DNA damage induced by potassium bromate in isolated rat renal proximal tubules and renal nuclei. Cancer Lett 87: 1-7.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Sai KT, Umemura T., Hasegawa R., Kurokawa Y. (1991). Relation of 8-hydroxydeoxyguanosine formation in rat kidney to lipid per-oxidation, glutathione level and relative organ weight after a single administration of potassium bromate. Jpn J Cancer Res 82: 165-169.[CrossRef][Web of Science]
  • Tanigawa HO, Maekawa A. (1987). Spontaneous mesotheliomas in Fischer rats—A histological and electron microscopic study. Toxicol Pathol 15: 157-163.[Web of Science][Medline] [Order article via Infotrieve]
  • Umemura T., Sai K., Takagi A., Hasegawa R., Kurokawa Y. (1995). A possible role for oxidative stress in potassium bromate (KBrO3) carcinogenesis. Carcinogenesis 16: 593-597.[Abstract/Free Full Text]
  • US Environmental Protection Agency (1998). National primary drinking water regulations: Disinfectants and disinfection byprod
  • ucts notice of data availability: Proposed rule, 40 CFR Parts 141-142. Fed Register 63: 15673-15692.
  • US Environmental Protection Agency (1998). Draft water quality criteria methodology revisions: Human health; notice. Fed Register 63: 43755-43828.
  • World Health Organization ( 1964). Seventh report on the specifications for the identity and purity of food additives and their toxicological evaluation: Emulsifiers, stabilizers, bleaching and maturing agents. WHO Tech Rep 281: 164.

Toxicologic Pathology, Vol. 28, No. 2, 253-266 (2000)
DOI: 10.1177/019262330002800205
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This Article
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What's this?