Pneumotoxicity of butylated hydroxytoluene applied dermally to CD-1 mice

Pneumotoxicity of butylated hydroxytoluene (BHT) applied to the skin of CD-1 mice was investigated and compared with that of butylated hydroxyanisole (BHA). To 6 groups of 10 male mice and 10 female mice 0.1 ml of dimethylsulfoxide (DMSO) solutions containing 0, 5, 10, 20, or 30 mg of BHT or 30 mg of BHA were topically applied 3 times weekly for 4 weeks. Between the 4th and 8th day BHT-treated mice exhibited respiratory distress with subsequent dose-dependent mortality. At autopsy dead animals were found to have congestion and enlargement of the lung with oozing of froth from the trachea. Histologically, collapse of the alveoli and dilatation of the alveolar ducts associated with degeneration or necrosis of type I alveolar epithelial cells were evident. The lethal effect of BHT was more manifest in female than in male mice. In contrast, none of the BHA-treated or control mice showed lung abnormalities. In another series of experiments to study the species difference of BHT pneumotoxicity, F-344 rats of both sexes and male Syrian golden hamsters were exposed to BHT by dermal application 3 times weekly for 4 weeks at a dose of 240 mg in rats or 480 mg in hamsters. However, no pulmonary alterations were observed in either species.