The
antioxidant food preservative
butylated hydroxyanisole (
BHA) was tested in an initiation-promotion protocol in which male F344 rats (6 wk old), 27 per group, were gavaged with a single dose of 200 mg
N-methyl-N'-nitro-N-nitrosoguanidine (
MNNG)/kg. After 3 wk on control diet, test diets containing 0, 60, 300, 1000, 3000, 6000 or 12,000 ppm
BHA were fed until termination of the experiment at approximately 110 wk, at which time most animals had died with stomach tumours.
MNNG caused a high incidence of tumours in the glandular stomach and forestomach of all groups. Administration of 12,000 and 6000 ppm
BHA, but not 3000 ppm or lower doses, caused statistically significant increases in the time-related incidence of
MNNG-induced forestomach tumours as analyzed by life table analysis.
BHA had no effect on the incidence of tumours in the glandular stomach or oesophagus. Tumour incidences in other organs were not related to
BHA dose. No increase in
hyperplasia in the oesophagus was evident in the high-dose
BHA-treated animals compared with the
MNNG-only group. This study provides corroboration that
BHA affects only forestomach
tumorigenesis and that the dose for enhancement of
tumorigenesis is at least 1500-fold greater than human exposure.