PMID- 34717176
OWN - NLM
STAT- MEDLINE
DCOM- 20220107
LR  - 20230102
IS  - 1873-6750 (Electronic)
IS  - 0160-4120 (Print)
IS  - 0160-4120 (Linking)
VI  - 158
DP  - 2022 Jan
TI  - Biotransformation of 2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine (TTBP-TAZ) 
      can contribute to high levels of 2,4,6-tribromophenol (2,4,6-TBP) in humans.
PG  - 106943
LID - S0160-4120(21)00568-7 [pii]
LID - 10.1016/j.envint.2021.106943 [doi]
AB  - 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 mug/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.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Zheng, Guomao
AU  - Zheng G
AD  - Paul H. O'Neill School of Public and Environmental Affairs Indiana University, 
      Bloomington, Indiana 47405, USA.
FAU - Melo, Luma
AU  - Melo L
AD  - School of Public Health, Indiana University, Bloomington, Indiana 47405, USA.
FAU - Chakraborty, Rishika
AU  - Chakraborty R
AD  - School of Public Health, Indiana University, Bloomington, Indiana 47405, USA.
FAU - Klaunig, James E
AU  - Klaunig JE
AD  - School of Public Health, Indiana University, Bloomington, Indiana 47405, USA.
FAU - Salamova, Amina
AU  - Salamova A
AD  - Paul H. O'Neill School of Public and Environmental Affairs Indiana University, 
      Bloomington, Indiana 47405, USA. Electronic address: asalamov@indiana.edu.
LA  - eng
GR  - R01 ES019620/ES/NIEHS NIH HHS/United States
GR  - R01 ES032392/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20211028
PL  - Netherlands
TA  - Environ Int
JT  - Environment international
JID - 7807270
RN  - 0 (2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine)
RN  - 0 (Flame Retardants)
RN  - 0 (Halogenated Diphenyl Ethers)
RN  - 0 (Hydrocarbons, Brominated)
RN  - 0 (Phenols)
RN  - 0 (Triazines)
RN  - YS6K3EU393 (2,4,6-tribromophenol)
SB  - IM
MH  - Animals
MH  - Biotransformation
MH  - Environmental Monitoring
MH  - *Flame Retardants/analysis/toxicity
MH  - Halogenated Diphenyl Ethers/toxicity
MH  - Humans
MH  - Hydrocarbons, Brominated
MH  - Phenols
MH  - Rats
MH  - Triazines/analysis/toxicity
PMC - PMC8688301
MID - NIHMS1751351
OTO - NOTNLM
OT  - 2,4,6-TBP
OT  - Biotransformation
OT  - In vitro
OT  - In vivo
OT  - TTBP-TAZ
COIS- Declaration of interests The authors declare that they have no known competing 
      financial interests or personal relationships that could have appeared to 
      influence the work reported in this paper.
EDAT- 2021/10/31 06:00
MHDA- 2022/01/08 06:00
PMCR- 2023/01/01
CRDT- 2021/10/30 20:10
PHST- 2021/08/13 00:00 [received]
PHST- 2021/09/24 00:00 [revised]
PHST- 2021/10/13 00:00 [accepted]
PHST- 2021/10/31 06:00 [pubmed]
PHST- 2022/01/08 06:00 [medline]
PHST- 2021/10/30 20:10 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - S0160-4120(21)00568-7 [pii]
AID - 10.1016/j.envint.2021.106943 [doi]
PST - ppublish
SO  - Environ Int. 2022 Jan;158:106943. doi: 10.1016/j.envint.2021.106943. Epub 2021 
      Oct 28.