Disposition of 4,4'-thiobis(6-t-butyl-m-cresol) in rats

LS Birnbaum, WC Eastin , L Johnson and HB Matthews

The absorption, distribution, metabolism, and excretion of 14C-labeled 4,4'-thiobis(6-t-butyl-m-cresol) (TBBC) was studied in male rats. Oral treatment showed a dose-related decrease in the rate of absorption due to a dose-related increase in retention time in the stomach. TBBC was incompletely absorbed after oral treatment, although the rate of absorption was proportional to the dose once the compound reached the small intestine. TBBC was rapidly distributed throughout the body with the liver being the major tissue depot. Significant amounts of the compound were also present in blood, muscle, skin, and adipose tissue. TBBC was initially rapidly cleared from all tissues except adipose, although a small percentage of the total dose tended to persist in liver and skin. Over half of the compound was excreted the first day, primarily via the bile into the feces. Little TBBC-derived radioactivity appeared in the urine. Metabolites of TBBC were present in the tissues at early times after administration, but were rapidly excreted. The major metabolite(s) appeared to be glucuronide conjugates of the parent compound. Thus, TBBC, an important antioxidant in the rubber and plastic industries, would tend to accumulate in liver and lipid-rich tissues upon chronic exposure, which if by the oral route, could also result in direct damage to the gastrointestinal tract.

Volume 11, Issue 6, pp. 537-543, 11/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics