PMID- 34607038
OWN - NLM
STAT- MEDLINE
DCOM- 20220107
LR  - 20220107
IS  - 1873-6750 (Electronic)
IS  - 0160-4120 (Linking)
VI  - 158
DP  - 2022 Jan
TI  - Use of (Q)SAR genotoxicity predictions and fuzzy multicriteria decision-making 
      for priority ranking of ethoxyquin transformation products.
PG  - 106875
LID - S0160-4120(21)00500-6 [pii]
LID - 10.1016/j.envint.2021.106875 [doi]
AB  - Ethoxyquin (EQ; 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline) has been used as 
      an antioxidant in feed for pets and food-producing animals, including farmed fish 
      such as Atlantic salmon. In Europe, the authorization for use of EQ as a feed 
      additive was suspended, due to knowledge gaps concerning the presence and 
      toxicity of EQ transformation products (TPs). Recent analytical studies focusing 
      on the detection of EQ TPs in farmed Atlantic salmon feed and fillets reported 
      the detection of a total of 27 EQ TPs, comprising both known and previously not 
      described EQ TPs. We devised and applied an in silico workflow to rank these EQ 
      TPs according to their genotoxic potential and their occurrence data in Atlantic 
      salmon feed and fillet. Ames genotoxicity predictions were obtained applying a 
      suite of five (quantitative) structure-activity relationship ((Q)SAR) tools, 
      namely VEGA, TEST, LAZAR, Derek Nexus and Sarah Nexus. (Q)SAR Ames genotoxicity 
      predictions were aggregated using fuzzy analytic hierarchy process (fAHP) 
      multicriteria decision-making (MCDM). A priority ranking of EQ TPs was performed 
      based on combining both fAHP ranked (Q)SAR predictions and analytical occurrence 
      data. The applied workflow prioritized four newly identified EQ TPs for further 
      investigation of genotoxicity. The fAHP-based prioritization strategy described 
      here, can easily be applied to other toxicity endpoints and groups of chemicals 
      for priority ranking of compounds of most concern for subsequent experimental and 
      mechanistic toxicology analyses.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Rasinger, J D
AU  - Rasinger JD
AD  - Institute of Marine Research (IMR), Bergen, Norway. Electronic address: 
      jra@hi.no.
FAU - Frenzel, F
AU  - Frenzel F
AD  - German Federal Institute for Risk Assessment (BfR), Dept. Food Safety, Berlin, 
      Germany.
FAU - Braeuning, A
AU  - Braeuning A
AD  - German Federal Institute for Risk Assessment (BfR), Dept. Food Safety, Berlin, 
      Germany.
FAU - Bernhard, A
AU  - Bernhard A
AD  - Institute of Marine Research (IMR), Bergen, Norway.
FAU - Ornsrud, R
AU  - Ornsrud R
AD  - Institute of Marine Research (IMR), Bergen, Norway.
FAU - Merel, S
AU  - Merel S
AD  - Institute of Marine Research (IMR), Bergen, Norway; National Research Institute 
      for Agriculture, Food and Environment (INRAE), Lyon-Villeurbanne, France.
FAU - Berntssen, M H G
AU  - Berntssen MHG
AD  - Institute of Marine Research (IMR), Bergen, Norway.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211001
PL  - Netherlands
TA  - Environ Int
JT  - Environment international
JID - 7807270
RN  - 0 (Antioxidants)
RN  - 9T1410R4OR (Ethoxyquin)
SB  - IM
MH  - *Animal Feed/analysis
MH  - Animals
MH  - Antioxidants
MH  - DNA Damage
MH  - *Ethoxyquin
MH  - Fishes
OTO - NOTNLM
OT  - Analytic hierarchy process
OT  - Antioxidants
OT  - Multicriteria decision-making
OT  - Mutagenicity
OT  - Risk assessment
OT  - Toxicity prediction
EDAT- 2021/10/05 06:00
MHDA- 2022/01/08 06:00
CRDT- 2021/10/04 20:17
PHST- 2021/06/03 00:00 [received]
PHST- 2021/08/16 00:00 [revised]
PHST- 2021/09/08 00:00 [accepted]
PHST- 2021/10/05 06:00 [pubmed]
PHST- 2022/01/08 06:00 [medline]
PHST- 2021/10/04 20:17 [entrez]
AID - S0160-4120(21)00500-6 [pii]
AID - 10.1016/j.envint.2021.106875 [doi]
PST - ppublish
SO  - Environ Int. 2022 Jan;158:106875. doi: 10.1016/j.envint.2021.106875. Epub 2021 
      Oct 1.