Liver response tests. IV. Application to short-term feeding studies with butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA)

Abstract

Preliminary studies involved oral administration to rats of 6 daily doses (500 mg/kg) of butylated hydroxytoluene (BHT; 3,5-di- tert-butyl-4-hydroxytoluene) or butylated hydroxyanisole (BHA; 3- tert-butyl-4-hydroxyanisole). Both BHA and BHT induced liver enlargement and increased daily output of urinary ascorbic acid. These changes paralleled each other closely in onset, degree and duration, being rapid but transient with BHA, and slower in onset yet more prolonged with BHT. Administration of BHA or BHT at a level of 0·1% in the diet of rats for 16 wk elicited similar changes, particularly in females. With BHT the effects were more pronounced and more prolonged, but despite continuation of treatment relative liver weight and urinary ascorbic acid had returned to control levels by 16 wk. In the case of BHA the effects were no longer manifest after 4 wk. There was no histopathological evidence of damage to the liver. Equally negative findings regarding liver response were obtained in the biochemical measurements and histochemical assessments of glucose 6-phosphatase and glucose 6-phosphate dehydrogenase activities. Both BHT and BHA brought about increases in adrenal weight. It is concluded that measurement of ascorbic acid excretion in the urine affords a promising means of detecting hyperfunctional liver enlargement and distinguishing it from toxic liver enlargement. Under the conditions of the present experiments neither BHT nor BHA exhibited evidence of hepatotoxicity.