PMID- 35468502
OWN - NLM
STAT- MEDLINE
DCOM- 20220524
LR  - 20220524
IS  - 1879-2448 (Electronic)
IS  - 0043-1354 (Linking)
VI  - 218
DP  - 2022 Jun 30
TI  - In vivo toxicity evaluations of halophenolic disinfection byproducts in drinking 
      water: A multi-omics analysis of toxic mechanisms.
PG  - 118431
LID - S0043-1354(22)00385-2 [pii]
LID - 10.1016/j.watres.2022.118431 [doi]
AB  - Halophenolic disinfection byproducts (DBPs) in drinking water have attracted 
      considerable concerns in recent years due to their wide occurrence and high 
      toxicity. The liver has been demonstrated as a major target organ for several 
      halophenolic DBPs. However, little is known about the underlying mechanisms of 
      liver damage caused by halophenolic DBPs. In this study, 2,4,6-trichlorophenol 
      (TCP), 2,4,6-tribromophenol (TBP) and 2,4,6-triiodiophenol (TIP) were selected as 
      representative halophenolic DBPs and exposed to C57BL/6 mice at an 
      environmentally-relevant concentration (0.5 mug/L) and two toxicological 
      concentrations (10 and 200 mug/L) for 12 weeks. Then, a combination of 
      histopathologic and biochemical examination, liver transcriptome, serum 
      metabolome, and gut microbiome was adopted. It was found that trihalophenol 
      exposure significantly elevated the serum levels of alkaline phosphatase and 
      albumin. Liver inflammation was observed at toxicological concentrations in the 
      histopathological examination. Transcriptome results showed that the three 
      trihalophenols could impact immune-related pathways at 0.5 mug/L, which further 
      contributed to the disturbance of pathways in infectious diseases and cancers. 
      Notably, TBP and TIP had higher immunosuppressive effects than TCP, which might 
      lead to uncontrolled infection and cancer. In terms of serum metabolic profiles, 
      energy metabolism pathway of citrate cycle and amino acid metabolism pathways of 
      valine, leucine, and isoleucine were also significantly affected. Integration of 
      the metabolomic and transcriptomic data suggested that a 12-week trihalophenol 
      exposure could prominently disturb the glutathione metabolism pathway, indicating 
      the impaired antioxidation and detoxification abilities in liver. Moreover, the 
      disorder of the intestinal flora could interfere with immune regulation and host 
      metabolism. This study reveals the toxic effects of halophenolic DBPs on 
      mammalian liver and provides novel insights into the underlying mechanisms of 
      hepatotoxicity.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Jiang, Xiaoqin
AU  - Jiang X
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, Nanjing, 210023, Jiangsu, China.
FAU - Shi, Peng
AU  - Shi P
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, Nanjing, 210023, Jiangsu, China.
FAU - Jiang, Liujing
AU  - Jiang L
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, Nanjing, 210023, Jiangsu, China.
FAU - Qiu, Jingfan
AU  - Qiu J
AD  - Key Laboratory of Pathogen Biology of Jiangsu Province, Department of Pathogen 
      Biology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.
FAU - Xu, Bin
AU  - Xu B
AD  - State Key Laboratory of Pollution Control and Resource Reuse, College of 
      Environmental Science and Engineering, Tongji University, Shanghai, 200092, 
      China.
FAU - Pan, Yang
AU  - Pan Y
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, Nanjing, 210023, Jiangsu, China. Electronic 
      address: panyang@nju.edu.cn.
FAU - Zhou, Qing
AU  - Zhou Q
AD  - State Key Laboratory of Pollution Control and Resource Reuse, School of the 
      Environment, Nanjing University, Nanjing, 210023, Jiangsu, China. Electronic 
      address: zhouqing@nju.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220408
PL  - England
TA  - Water Res
JT  - Water research
JID - 0105072
RN  - 0 (Chlorophenols)
RN  - 0 (Disinfectants)
RN  - 0 (Drinking Water)
RN  - 0 (Water Pollutants, Chemical)
SB  - IM
MH  - Animals
MH  - *Chlorophenols/toxicity
MH  - *Disinfectants/analysis/toxicity
MH  - Disinfection
MH  - *Drinking Water/analysis
MH  - Halogenation
MH  - Mammals
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Water Pollutants, Chemical/chemistry
MH  - *Water Purification
OTO - NOTNLM
OT  - Drinking water
OT  - Immunotoxicity
OT  - In vivo toxicity
OT  - Multi-omics
OT  - Phenolic disinfection byproducts
EDAT- 2022/04/26 06:00
MHDA- 2022/05/25 06:00
CRDT- 2022/04/25 20:18
PHST- 2021/12/08 00:00 [received]
PHST- 2022/03/18 00:00 [revised]
PHST- 2022/04/06 00:00 [accepted]
PHST- 2022/04/26 06:00 [pubmed]
PHST- 2022/05/25 06:00 [medline]
PHST- 2022/04/25 20:18 [entrez]
AID - S0043-1354(22)00385-2 [pii]
AID - 10.1016/j.watres.2022.118431 [doi]
PST - ppublish
SO  - Water Res. 2022 Jun 30;218:118431. doi: 10.1016/j.watres.2022.118431. Epub 2022 
      Apr 8.