Evidence of a Threshold Dose for Promotion of Hepatocarcinogenesis by Hexachlorobenzene in a Rat Medium-Term Liver Bioassay

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  • Ichihara Toshio
    Department of Experimental Pathology and Tumor Biology, Nagoya City University Medical Sciences DIMS Institute of Medical Science
  • Imai Norio
    Department of Experimental Pathology and Tumor Biology, Nagoya City University Medical Sciences DIMS Institute of Medical Science
  • Toda Yosuke
    DIMS Institute of Medical Science
  • Hagiwara Akihiro
    DIMS Institute of Medical Science
  • Tamano Seiko
    DIMS Institute of Medical Science
  • Shirai Tomoyuki
    Department of Experimental Pathology and Tumor Biology, Nagoya City University Medical Sciences

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The potential of hexachlorobenzene (HCB) to promote the development of glutathione S-transferase placental form (GST-P) positive foci in the male F344/DuCrj (F344) rat liver was evaluated with 11 different dietary doses, ranging from 0.002 to 75 ppm, using a medium-term liver bioassay system. No mortalities caused by HCB treatment were encountered, and no clinical changes were apparent. The numbers and areas of GST-P positive foci in the 0.002 ppm to 40 ppm groups were comparable with the control values, but those in the 75 ppm HCB group were slightly, albeit not significantly, increased. The present results indicate that HCB exerts weak promotion potential for rat liver carcinogenesis, but only at a dietary level of 75 ppm (5.27 mg/kg/day), thus providing evidence for the existence of a threshold.

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