Birnbaum L S, Eastin W C, Johnson L, Matthews H B
Drug Metab Dispos. 1983 Nov-Dec;11(6):537-43.
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.
在雄性大鼠中研究了14C标记的4,4'-硫代双(6-叔丁基间甲酚)(TBBC)的吸收、分布、代谢和排泄。口服给药显示，由于在胃中的停留时间呈剂量相关增加，吸收率呈剂量相关下降。口服给药后TBBC吸收不完全，尽管一旦该化合物到达小肠，吸收率与剂量成正比。TBBC迅速分布于全身，肝脏是主要的组织储存部位。该化合物在血液、肌肉、皮肤和脂肪组织中也有大量存在。TBBC最初从除脂肪组织外的所有组织中迅速清除，尽管总剂量的一小部分倾向于在肝脏和皮肤中持续存在。超过一半的化合物在第一天排出，主要通过胆汁排入粪便。尿液中几乎没有TBBC衍生的放射性。给药后早期，TBBC的代谢产物存在于组织中，但迅速排出。主要代谢产物似乎是母体化合物的葡萄糖醛酸共轭物。因此，TBBC是橡胶和塑料工业中的一种重要抗氧化剂，长期接触后会倾向于在肝脏和富含脂质的组织中蓄积，如果通过口服途径，也可能导致胃肠道直接损伤。
