Histologic and Autoradiographic Studies on the Forestomach of Hamsters Treated With 2-tert-Butylated Hydroxyanisole, 3-tert-Butylated Hydroxyanisole, Crude Butylated Hydroxyanisole, or Butylated Hydroxytoluene2

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Abstract
The inductions of hyperplasia and neoplastic lesions in the forestomach of Syrian golden hamsters by 2-tert-butylated hydroxyanisole [(2-tert-BHA) CAS: 121-00-6], 3-tert-butylated hydroxyanisole [(3-tert-BHA) CAS: 88-32-4], crude butylated hydroxyanisole [(BHA) CAS: 25013-16-5], and butylated hydroxytoluene [(BHT) CAS: 128-37-0] were compared histopathologically and autoradiographically. In hamsters fed the 2-tert-BHA diet, severe hyperplasia developed from week 4, reaching a maximum level in week 16 of 0.56 cm/10 cm basement membrane (bm), and papillomatous lesions appeared in week 16 (0.13 cm/10 cm bm). In hamsters fed 3-tert-BHA or crude BHA, severe hyperplasia developed from week 1, which reached a maximum level in week 4 of 3.63 cm/10 cm bm with 3-tert-BHA and 5.10 cm/10 cm with crude BHA; it then decreased. Papillomatous lesions were found in week 3 in hamsters fed 3-tert-BHA and in week 4 in hamsters fed crude BHA; they increased to maximum levels in week 16 of 0.50 cm/10 cm bm with 3-tert-BHA and 0.29 cm/10 cm bm with crude BHA. Mild hyperplasia occurred slightly more often in hamsters fed the BHT diet than in the control group. BHT induced no severe hyperplasia and papillomatous lesions. Changes in the labeling index of the forestomach epithelium paralleled the histologic changes, except in hamsters fed the BHT diet in which no significant increase in the labeling index was observed throughout the experiment. These data suggest that the tumorigenic action of crude BHA on hamster forestomach is largely due to 3-tert-BHA and that BHT does not induce forestomach tumors in hamsters.