Toxicity of butylated hydroxytoluene in mouse following oral administration

Male Swiss--Webster mice were given 400 mg/kg of butylated hydroxytoluene ([methyl-14C]toluene) by stomach tube. Radioactivity was measured in plasma, lung, liver and kidney from 0.5 h to 10 days later. Radioactivity associated with butylated hydroxytoluene (BHT) or its metabolites was highest in plasma and all tissues examined between 1 and 12 h after administration. After 24 h, less than 1% of the administered dose remained in the lung, kidney or liver. One day after BHT, DNA synthesis in lung increased and, on days 3, 4 and 5, was 6--8 times as high as in controls. DNA content of the lungs almost doubled. Synthesis and net increase of pulmonary DNA were dose-dependent. If BHT was given orally following injection of one single dose of urethane, adenoma formation in lung was enhanced. It is concluded that BHT, given by stomach tube and in doses higher than 100 mg/kg, produces extensive cell proliferation in mouse lung and acts as a promoting agent in adenoma development.