A carcinogenesis reversibility study of the effects of butylated hydroxyanisole on the forestomach and urinary bladder in male Fischer 344 rats.
A reversibility study was initiated to determine if the length of feeding with 2% butylated hydroxyanisole (BHA) altered the incidence of forestomach lesions observed after a 24-month observation period. Groups of male Fischer 344 rats were fed 2% BHA for 0, 3, 6, 12, and 24 months and then the basal diet for the completion of the 24-month experimental period. Subgroups were serially sacrificed for histopathological examination and [methyl-3H]thymidine radioautography at the time when each group of animals was transferred to the basal diet and also at 15 months. The results showed that except for carcinomas and some epithelial downgrowths, cellular proliferation, measured by radioautography in the epithelium lining the greater and the lesser curvature of the forestomach, remained dependent on the continuous presence of 2% BHA for, at least, 12 months. Superficial hyperplasias, inflammatory lesions and many of the papillomas regressed after cessation of treatment at 12 months. The epithelial downgrowths did not appear to enlarge after the BHA was withdrawn. The squamous cell carcinomas occurred in almost identical yields whether the rats were fed 2% BHA for 12 months and then returned to the basal diet for 12 months or received 2% BHA continuously for 24 months. It is shown here that at several times, 2% BHA stimulated the [methyl-3H]thymidine labelling index of the transitional epithelium of the urinary bladder and that at 3 months the no observed effect level was greater than 0.5% BHA. The significance of the studies on the forestomach and bladder epithelia are discussed. It is concluded that the lesions induced by BHA are most unlikely to be relevant to humans exposed to much lower levels of BHA.
Nera
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EA
Toxicology Research Division, Bureau of Chemical Safety, Health Protection Branch, Ottawa, Ontario, Canada.
Iverson
F
F
Lok
E
E
Armstrong
C L
CL
Karpinski
K
K
Clayson
D B
DB
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002083:Butylated Hydroxyanisole / Q000009:adverse effects*; D002273:Carcinogens; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013270:Stomach / Q000187:drug effects; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology; D013936:Thymidine / Q000031:analogs & derivatives; D014316:Tritium; D001743:Urinary Bladder / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
D002273:Carcinogens; D014316:Tritium; D002083:Butylated Hydroxyanisole; C012439:methylthymidine; D013936:Thymidine