Haemorrhages due to defective blood coagulation do not occur in mice and guinea-pigs fed butylated hydroxytoluene, but nephrotoxicity is found in mice.

Groups of ten male Slc:ddY mice were fed a purified diet containing butylated hydroxytoluene (BHT) at levels of 0, 1.35, 1.75, 2.28, 2.96, 3.85 or 5.00%. They were kept in cages with soft-wood chips as bedding for 30 days. Groups of five Slc:ddY male mice were kept in cages with stainless-steel wire-mesh bottoms (without wood-chip bedding) and fed BHT at 0, 0.5, 1.0 or 2.0% in the diet for 21 days. Male Crj:Hartley guinea-pigs were given a purified ration containing BHT at levels of 0, 0.125 or 0.25% (five animals per group) for 14 days, or at 0, 0.5, 1.0 or 2.0% for 17 days (six animals per group). When BHT was given to mice housed in the mesh-bottomed cages there were one, one and two deaths during the experiment in the 0.5, 1.0 and 2.0% dose groups, respectively. Lung haemorrhages were observed in these dead mice, but in all other mice and guinea-pigs no haemorrhages were found. Indices of prothrombin time and kaolin-activated partial thromboplastin time were significantly decreased by up to 30 and 40%, respectively, in the mice kept on wood-chip bedding, and by up to 40 and 60% in the mice kept in cages with wire bottoms. In guinea-pigs, the prothrombin index was significantly reduced only in the 1.0% BHT group. We conclude that the BHT-induced lung haemorrhages in mice are not caused by a severe reduction in the coagulation process, as they are in rats, and that BHT does not cause bleeding like that observed in rats. However, dose-related toxic nephrosis was found in mice given 1.35-5.0% BHT in the diet. The nephrotoxic ED50(1 month) was 2.3 g/kg body weight/day. The results suggest that an extremely large dose of BHT can cause renal toxicity in mice.