Tests were carried out to determine the toxic outcome of the interactions between butylated-hydroxytoluene (128370) (BHT) and a variety of other phenolic derivatives by investigating the in-vitro generation of BHT-quinone-methide in the presence of peroxidase enzymes, the effects of phenols on this reaction, and its in-vivo significance. In-vitro tests revealed that butylated-hydroxyanisole (25013165) (BHA) increased both the peroxidase binding of BHT to microsomal protein and the generation of BHT-quinone-methide. The metabolic activation of BHT was also promoted by eugenol (97530), methylparaben (99763), vanillin (121335), guaiacol (90051), ferulic- acid (1135246), and a series of other phenolic additives, but to a lesser degree than that induced by BHA. In-vitro studies carried out with lung, bladder, kidney medulla, and intestinal microsomes obtained from both animals and man, in the presence of hydrogen- peroxide (7722841) or arachidonic-acid (506321), supported the interaction of BHT and BHA. Subcutaneous injection of BHA to male CD- 1-mice, prior to the intraperitoneal injection of BHT, increased the ratio of lung to body weight of the animals as compared to mice treated with BHT alone.