Investigations on cell proliferation in B6C3F1 mouse liver by diethanolamine

Diethanolamine (DEA) has been shown to induce liver tumours in B6C3F1 mice in a previous 2-year dermal study. To elucidate the mode of action groups of eight male and eight female B6C3F1 mice were dermally exposed to daily DEA doses of 0 or 160 mg/kg body weight/day for 1 week. Reversibility was assessed after a 3-week treatment-free recovery period. Subsequently groups of 10 male B6C3F1 mice were dermally exposed to daily DEA doses of 0 or 160 mg/kg body weight for 1, 4 or 13 weeks. Finally, groups of 8 male B6C3F1 mice were dermally exposed to daily DEA doses of 0, 10, 20, 40, 80, and 160 mg/kg body weight for 1 and 13 weeks. Following a 1-week treatment, DEA caused increased cell proliferation (5-bromo-2′-deoxyuridine (BrdU) method) in zone 3 (central vein region) of the liver lobules at 160 mg/kg body weight. Reversibility of liver cell proliferation was demonstrated in the recovery phase. In the subsequent studies increased cell proliferation was observed at 10 mg/kg body weight or higher after 13 weeks of treatment. These results support the hypothesis that sustained liver cell proliferation is a potential non genotoxic mode of action by which DEA promotes liver tumours in B6C3F1 mice.