The metabolism of 2,6-di-tert.-butyl-4-hydroxymethylphenol (Ionox 100) in the dog and rat.
1. A single oral dose of [(14)C]Ionox 100 to rats is almost entirely eliminated in 11 days: 89.1-107.2% of the (14)C is excreted and 0.29+/-0.02% of the dose is present in the carcass plus viscera after removal of the gut. Rats exhibit an individual variation in the elimination pattern, 15.6-70.8% of (14)C being excreted in the urine and 75.2-27.0% in the faeces during 11 days. 2. After the oral administration of [(14)C]Ionox 100 to dogs, 87.1-90.3% of the (14)C is excreted in the faeces and urine during 4 days. 3. Dogs and rats do not show a species difference in this pattern of elimination. 4. The rate of elimination from dogs and rats given a single dose of Ionox 100 is not affected by the size of the dose and the presence of triglyceride fat in the diet. 5. Ionox 100 is completely metabolized in dogs and rats: unchanged Ionox 100 is absent from the urine and faeces, and from the carcass when elimination is complete. In rats, 3,5-di-tert.-butyl-4-hydroxybenzoic acid accounts for 50-85% of a dose of Ionox 100 and (3,5-di-tert.-butyl-4-hydroxybenzoyl beta-d-glucopyranosid)uronic acid for 47-10%; in dogs, the unconjugated acid accounts for 85% and the ester glucuronide for 10-12%. 3,5-Di-tert.-butyl-4-hydroxyhippuric acid is not formed. Other metabolites, which have been detected in small quantity in the faeces and urine of animals dosed with Ionox 100, have not been identified. 6. 3,5-Di-tert.-butyl-4-hydroxybenzoic acid and (3,5-di-tert.-butyl-4-hydroxybenzoyl beta-d-glucopyranosid)uronic acid are also the major metabolites of Ionol (2,6-di-tert.-butyl-p-cresol) in rats. 7. The elimination of Ionox 100 metabolites from rats is faster than that of Ionol and its metabolites. Unlike Ionol, unchanged Ionox 100 could not be detected in the bodies of these animals.
Wright
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Tunstall Laboratory, Shell Research Ltd., Sittingbourne, Kent.
Akintonwa
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Crowne
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Hathway
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