Lung hemorrhagic toxicity of butylated hydroxyanisole in the rat

Male Sprague-Dawley rats were injected intraperitoneally (i.p.) with butylated hydroxyanisole (BHA) at doses of 0, 1, 4, 16, 64, 256, 384, 576, 864, 1296 and 1944 mg/kg/day for 7 days. Deaths occurred in a dose- and time-dependent manner when BHA was given in amounts greater than 576 mg/kg. The LD50 was 881 (484-1440) mg/kg. Intracranial hemorrhage was found in the dead rats, and lung hemorrhage was observed in the survivors given BHA at doses greater than 384 mg/kg/day. Histopathologically, intra-alveolar hemorrhages, thickening of alveoli and deposition of lipids in the lungs were observed. The prothrombin index was decreased only in rats given BHA at a level of 384 mg/kg/day. These observations suggest that BHA and/or its metabolite cause pulmonary hemorrhagic damage in rats. The mechanism of hemorrhage may be different from that of bleeding induced by butylated hydroxytoluene.