Route of administration determines whether chloroform enhances or inhibits cell proliferation in the liver of B6C3F1 mice.

Chloroform administered by gavage has been shown to induce liver cancer in B6C3F1 mice; however, when administered in the drinking water, chloroform inhibited liver cancer in mice. The effect of chloroform administered by these two routes upon cell proliferation in mouse liver was determined. Female B6C3F1 mice were divided into five treatment groups: (1) chloroform (263 mg/kg body wt) by gavage in corn oil, (2) 1,800 ppm chloroform in drinking water, (3) 1,800 ppm chloroform in drinking water plus 10 ml/kg body wt corn oil by gavage, (4) 10 ml/kg body wt corn oil by gavage, and (5) untreated controls. Five days prior to termination, the mice were implanted subcutaneously with a 7-day osmotic minipump containing 30 mg/ml bromodeoxyuridine. Mice were terminated after 5, 12, 33, and 159 days of exposure. Chloroform administered by gavage in corn oil increased cell proliferation at all terminations, while, when administered in drinking water, cell proliferation was inhibited on Days 5 and 12. At 33 and 159 days, chloroform administered in the drinking water did not affect cell proliferation, even though the dose received by the animals was comparable to that given in corn oil by gavage. Therefore, cell proliferation was enhanced only by chloroform administered in corn oil by gavage, which corresponds to the hepatocarcinogenicity of chloroform administered by this route.