Gastric retention and delayed absorption of a large dose of butylated hydroxytoluene in the rat

Abstract

1. After a single oral dose of 800 mg/kg of butylated hydroxytoluene to rats, the plasma concentration of 2,6-di-tert-butyl-4-methylene-2,5-cyclohexadienone (BHT quinone methide), an active metabolite of BHT, reached a maximum 18 h after dosing.

2. The gastrointestinal content of BHT remained constant from 0.5 to 12 h, and began to decline 18 h after dosing.

3. BHT concentrations in epididymal and subcutaneous adipose tissues also attained maxima 18 h after dosing.

4. Volumes and weights of stomachs and contents, and volumes of gastric contents of rats given 800 mg/kg BHT, were 2-3 times larger than those of controls 4-7 h after dosing, while there were no significant differences at 24-27 h after dosing.

5. Retention of ingested material in the stomachs was also observed when 18-h starved rats were given 800 mg/kg BHT.

6. Thirty minutes after intraduodenal administration of 800 mg/kg BHT to anaesthetized rats, BHT, but not BHT quinone methide, was 0.4–1.4 μg/ml in portal vein plasma. No BHT was detected in plasma from the aorta descendens. BHT and/or BHT radical, and BHT alone, were also found in liver and epididymal adipose tissue at 7-20 and 25-40/μg/g wet weight, respectively.

7. These results indicate that delay in attainment of maximum concentration of BHT or its metabolites in internal organs may be due to the long retention in the stomach, caused by high dosage and the inhibitory effect of BHT on gastric function. Moreover, most BHT may not enter lymphatic fluid but it can be absorbed into portal blood.