2,4,6-Tribromophenol (2,4,6-TBP) is a brominated flame retardant that accumulates in human tissues and is a potential toxicant. Previous studies found 2,4,6-TBP levels in human tissues were significantly higher than those of brominated flame retardants measured in the same samples. In contrast, the levels of 2,4,6-TBP in the environment and foodstuff are not elevated, suggesting a low potential for direct intake through environmental exposure or diet. Here, we hypothesized that high levels of 2,4,6-TBP in human tissues are partially from the indirect exposure sources, such as biotransformation of highly brominated substances. We conducted in vitro assays utilizing human and rat liver microsomes to compare the biotransformation rates of four highly brominated flame retardants, which could potentially transform to 2,4,6-TBP, including decabromodiphenyl ethane (DBDPE), 2,4,6-tris-(2,4,6-tribromophenoxy)-1,3,5-triazine (TTBP-TAZ), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), and tetrabromobisphenol A (TBBPA). Our results show that TTBP-TAZ rapidly metabolizes in both human and rat liver microsomes with a half-life of 1.1 and 2.2 h, respectively, suggesting that TTBP-TAZ is a potential precursor of 2,4,6-TBP. In contrast, 2,4,6-TBP was not formed as a result of biotransformation of TBBPA, BTBPE, and DBDPE in both human and rat liver microsomes. We applied suspect and target screening to explore the metabolic pathways of TTBP-TAZ and identified 2,4,6-TBP as a major metabolite of TTBP-TAZ accounting for 87% of all formed metabolites. These in vitro results were further tested by an in vivo experiment in which 2,4,6-TBP was detected in the rat blood and liver at concentrations of 270 ± 110 and 50 ± 14 μg/g lipid weight, respectively, after being exposed to 250 mg/kg body weight/day of TTBP-TAZ for a week. The hepatic mRNA expression demonstrated that TTBP-TAZ significantly activates the aryl hydrocarbon receptor (AhR) and promotes fatty degeneration (18 and 28-fold change compared to control, respectively) in rats.

2,4,6-三溴苯酚 (2,4,6-TBP) 是一种溴化阻燃剂，会在人体组织中蓄积，是一种潜在的有毒物质。先前的研究发现，人体组织中的 2,4,6-TBP 水平明显高于在相同样本中测得的溴化阻燃剂水平。相比之下，环境和食物中 2,4,6-TBP 的水平并未升高，表明通过环境暴露或饮食直接摄入的可能性较低。在这里，我们假设人体组织中高水平的 2,4,6-TBP 部分来自间接暴露源，例如高溴物质的生物转化。我们在体外进行利用人和大鼠肝微粒体进行的测定比较四种高度溴化阻燃剂的生物转化率，这些阻燃剂可能转化为 2,4,6-TBP，包括十溴二苯乙烷 (DBDPE)、2,4,6-三-(2, 4,6-三溴苯氧基)-1,3,5-三嗪 (TTBP-TAZ)、1,2-双(2,4,6-三溴苯氧基)乙烷 (BTBPE) 和四溴双酚 A (TBBPA)。我们的结果显示 TTBP-TAZ 在人和大鼠肝微粒体中快速代谢，半衰期分别为 1.1 和 2.2 小时，表明 TTBP-TAZ 是 2,4,6-TBP 的潜在前体。相反，2,4,6-TBP 不是由于 TBBPA、BTBPE 和 DBDPE 在人和大鼠肝微粒体中的生物转化而形成的。我们应用可疑和目标筛选来探索 TTBP-TAZ 的代谢途径并确定 2,4, 6-TBP 作为 TTBP-TAZ 的主要代谢物，占所有形成的代谢物的 87%。这些体外结果通过体内实验进一步检验，其中在大鼠血液和肝脏中检测到浓度分别为 270±110 和 50±14 μg/g 250 mg/kg 体重/天的 TTBP-TAZ，持续一周。肝脏 mRNA 表达表明 TTBP-TAZ 显着激活大鼠的芳基烃受体 ( AhR ) 并促进脂肪变性（与对照相比分别有 18 倍和 28 倍的变化）。