The phenolic antioxidant butylated hydroxytoluene (BHT) was patented in 1947 and received approval for use as a food additive and preservative by the Food and Drug Administration (FDA) in 1954. Since 1959, BHT has been generally recognized as safe (GRAS) for use in foods and is one of the most commonly used antioxidants in foods containing fats.
A bioassay of BHT for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice.
Groups of 50 rats and 50 mice of each sex were administered BHT at one of two doses, either 3,000 or 6,000 ppm; the rats for 105 weeks and the mice for 107 or 108 weeks. Matched controls consisted of 20 untreated rats and 20 untreated mice of each sex. All surviving animals were killed at the end of administration of the test chemical.
Mean body weights of the dosed rats and mice were lower than those of the corresponding controls and were dose related throughout most of the bioassay. Survival was not affected significantly in the dosed groups of rats or mice, and the survival was 60% or greater in all dosed or control groups of rats and mice of each sex at the end of the bioassay. Sufficient number of animals were at risk for the development of late-appearing tumors.
Alveolar/bronchiolar carcinomas or adenomas occurred in the female mice at a significant incidence in the low-dose group (P=0.009) but not in the high dose group, and the incidences were not significantly dose related (control 1/20, low-dose 16/46, high-dose 7/50). Thus, these lung tumors in the female cannot clearly be related to the administration of the BHT. No tumors occurred in either male or female rats at incidences that were significantly higher in dosed groups than in corresponding control groups. Nonneoplastic lesions that may have been related to the administration of the test chemical included focal alveolar histiocytosis at increased incidences in the dosed female rats and various lesions of the liver at increased incidences in the dosed male mice.
It is concluded that under the conditions of this bioassay, BHT was not carcinogenic for F344 rats or B6C3F1 mice.