2,6-di-tert-butyl-4-methylene-2,5-cyclohexadienone (BHT quinone methide): an active metabolite of BHT causing haemorrhages in rats

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Abstract
Male Sprague-Dawley rats and male ICR mice, species respectively susceptible and resistant to the haemorrhagic effect of butylated hydroxytoluene (BHT), were administered BHT quinone methide (2,6-di-tert-butyl4-methylene-2,5-cyclohexadienone) orally; 24 or 48 h later the plasma concentrations of blood coagulation factors II (prothrombin), VII, IX and X were determined. BHT quinone methide caused a decrease in factors II, VII, IX and X in a dose-dependent manner after 48 h, while a similar dose of BHT did not. Haemorrhages in epididymis or thymus were found in BHT quinone methide-treated rats. These findings may support the belief that BHT quinone methide is an active metabolite which disturbs the vitamin K redox cycle in BHT-induced haemorrhage.