PMID- 34119701
OWN - NLM
STAT- MEDLINE
DCOM- 20210930
LR  - 20210930
IS  - 1872-7077 (Electronic)
IS  - 1382-6689 (Linking)
VI  - 87
DP  - 2021 Oct
TI  - Assessing the chemical-induced estrogenicity using in silico and in vitro 
      methods.
PG  - 103688
LID - S1382-6689(21)00106-X [pii]
LID - 10.1016/j.etap.2021.103688 [doi]
AB  - Multiple substances are considered endocrine disrupting chemicals (EDCs). 
      However, there is a significant gap in the early prioritization of EDC's effects. 
      In this work, in silico and in vitro methods were used to model estrogenicity. 
      Two Quantitative Structure-Activity Relationship (QSAR) models based on Logistic 
      Regression and REPTree algorithms were built using a large and diverse database 
      of estrogen receptor (ESR) agonism. A 10-fold external validation demonstrated 
      their robustness and predictive capacity. Mechanistic interpretations of the 
      molecular descriptors (C-026, nArOH,PW5, B06[Br-Br]) used for modelling suggested 
      that the heteroatomic fragments, aromatic hydroxyls, and bromines, and the 
      relative bond accessibility areas of molecules, are structural determinants in 
      estrogenicity. As validation of the QSARs, ESR transactivity of thirteen 
      persistent organic pollutants (POPs) and suspected EDCs was tested in vitro using 
      the MMV-Luc cell line. A good correspondence between predictions and experimental 
      bioassays demonstrated the value of the QSARs for prioritization of ESR agonist 
      compounds.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Goya-Jorge, Elizabeth
AU  - Goya-Jorge E
AD  - ProtoQSAR SL., CEEI (Centro Europeo de Empresas Innovadoras), Parque Tecnologico 
      de Valencia, 12 Av. Benjamin Franklin, 46980, Paterna, Valencia, Spain; 
      Department of Food Science, Faculty of Veterinary Medicine-FARAH, University of 
      Liege, 10 Av. Cureghem, 4000, Sart-Tilman, Liege, Belgium. Electronic address: 
      egoya@uliege.be.
FAU - Amber, Mazia
AU  - Amber M
AD  - The Institute for Global Food Security, School of Biological Sciences, Queen's 
      University Belfast, 19 Chlorine Gardens, BT9 5DL, Belfast, Northern Ireland, 
      United Kingdom. Electronic address: m.amber@qub.ac.uk.
FAU - Gozalbes, Rafael
AU  - Gozalbes R
AD  - ProtoQSAR SL., CEEI (Centro Europeo de Empresas Innovadoras), Parque Tecnologico 
      de Valencia, 12 Av. Benjamin Franklin, 46980, Paterna, Valencia, Spain; MolDrug 
      AI Systems SL, 45 Olimpia Arozena Torres, 46018, Valencia, Spain. Electronic 
      address: rgozalbes@protoqsar.com.
FAU - Connolly, Lisa
AU  - Connolly L
AD  - The Institute for Global Food Security, School of Biological Sciences, Queen's 
      University Belfast, 19 Chlorine Gardens, BT9 5DL, Belfast, Northern Ireland, 
      United Kingdom. Electronic address: l.connolly@qub.ac.uk.
FAU - Barigye, Stephen J
AU  - Barigye SJ
AD  - ProtoQSAR SL., CEEI (Centro Europeo de Empresas Innovadoras), Parque Tecnologico 
      de Valencia, 12 Av. Benjamin Franklin, 46980, Paterna, Valencia, Spain; MolDrug 
      AI Systems SL, 45 Olimpia Arozena Torres, 46018, Valencia, Spain. Electronic 
      address: sjbarigye@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20210610
PL  - Netherlands
TA  - Environ Toxicol Pharmacol
JT  - Environmental toxicology and pharmacology
JID - 9612020
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Estrogens)
RN  - 0 (Receptors, Estrogen)
SB  - IM
MH  - Algorithms
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Computer Simulation
MH  - Endocrine Disruptors/chemistry/classification/*toxicity
MH  - Estrogens/chemistry/classification/*toxicity
MH  - Humans
MH  - Models, Chemical
MH  - Quantitative Structure-Activity Relationship
MH  - Receptors, Estrogen/antagonists & inhibitors/*metabolism
OTO - NOTNLM
OT  - Endocrine disruptor
OT  - Estrogen receptor
OT  - Persistent organic pollutant
OT  - Predictive toxicology
OT  - QSAR
OT  - Reporter gene assay
EDAT- 2021/06/14 06:00
MHDA- 2021/10/01 06:00
CRDT- 2021/06/13 20:42
PHST- 2021/03/04 00:00 [received]
PHST- 2021/06/07 00:00 [revised]
PHST- 2021/06/08 00:00 [accepted]
PHST- 2021/06/14 06:00 [pubmed]
PHST- 2021/10/01 06:00 [medline]
PHST- 2021/06/13 20:42 [entrez]
AID - S1382-6689(21)00106-X [pii]
AID - 10.1016/j.etap.2021.103688 [doi]
PST - ppublish
SO  - Environ Toxicol Pharmacol. 2021 Oct;87:103688. doi: 10.1016/j.etap.2021.103688. 
      Epub 2021 Jun 10.