PMID- 27129947
OWN - NLM
STAT- MEDLINE
DCOM- 20170512
LR  - 20170512
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 376
DP  - 2017 Feb 1
TI  - Toxicity evaluation of the photoprotective compound LQFM048: Eye irritation, skin 
      toxicity and genotoxic endpoints.
PG  - 83-93
LID - S0300-483X(16)30037-3 [pii]
LID - 10.1016/j.tox.2016.04.007 [doi]
AB  - A new molecule, LQFM048, originally designed through molecular hybridization 
      using green chemistry approach, is in development as a photoprotective agent. Eye 
      irritation, skin toxicity and genotoxicity evaluations are mandatory for 
      predicting health risks. In this context, the purpose of this study was to 
      investigate the eye irritation potential of LQFM048 by combining Short Time 
      Exposure (STE), Bovine Corneal Opacity and Permeability (BCOP) associated with 
      corneal histomorphometry and Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). 
      Additionally, skin toxicity was evaluated by interleukin-18 production in the 
      HaCaT keratinocyte, Local Lymph Node Assay (LLNA:BrdU-ELISA) method, 3T3 Neutral 
      red uptake (NRU) assay and in vivo phototoxicity test. Genotoxic potential of 
      LQFM048 was also analyzed by cytokinesis-block micronucleus assay (MNvit 
      test-cytoB) in HepG2 cells. Our results showed that LQFM048 did not induce eye 
      irritation and it was classified as UN GHS No Category for both STE and BCOP 
      assays and non-irritating for HET-CAM test. LQFM048 showed non-potential skin 
      sensitization with stimulation index (SI=0.7) in the LLNA:BrdU-ELISA method. 
      Corroborating in vivo tests, it did not promote significant cytotoxicity in HaCaT 
      cells and it showed similar levels of IL-18 when compared to control. 
      Furthermore, LQFM048 induced non-phototoxic potential with photo-irritation 
      factor (PIF) and mean photo effect (MPE) of 1 and -0.138, respectively, for 3T3 
      cells. Similarly, it was not phototoxic for in vivo testing with or without 
      exposure to UVA, showing SI values of 1 and 1.2, respectively. The micronucleus 
      test showed that LQFM048 was not genotoxic, under the conditions tested.In 
      conclusion, LQFM048, a heterocyclic compound obtained through an environmentally 
      acceptable simple synthetic route, seems to be safe for human use, especially for 
      the development of a new sunscreen product, since it is neither an eye irritant, 
      nor a contact allergen, nor mutagenic and nor phototoxic.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - de Avila, Renato Ivan
AU  - de Avila RI
AD  - Laboratorio de Farmacologia e Toxicologia Celular-LFTC/FarmaTec, Faculdade de 
      Farmacia, Universidade Federal de Goias, Goiania, GO, Brazil.
FAU - de Sousa Vieira, Marcelo
AU  - de Sousa Vieira M
AD  - Laboratorio de Farmacologia e Toxicologia Celular-LFTC/FarmaTec, Faculdade de 
      Farmacia, Universidade Federal de Goias, Goiania, GO, Brazil.
FAU - Gaeti, Marilisa Pedroso Nogueira
AU  - Gaeti MP
AD  - Laboratorio de Tecnologia Farmaceutica-FarmaTec, Faculdade de Farmacia, 
      Universidade Federal de Goias, Goiania, GO, Brazil.
FAU - Moreira, Larissa Cleres
AU  - Moreira LC
AD  - Laboratorio de Farmacologia e Toxicologia Celular-LFTC/FarmaTec, Faculdade de 
      Farmacia, Universidade Federal de Goias, Goiania, GO, Brazil.
FAU - de Brito Rodrigues, Lais
AU  - de Brito Rodrigues L
AD  - Laboratorio de Farmacologia e Toxicologia Celular-LFTC/FarmaTec, Faculdade de 
      Farmacia, Universidade Federal de Goias, Goiania, GO, Brazil.
FAU - de Oliveira, Gisele Augusto Rodrigues
AU  - de Oliveira GA
AD  - Laboratorio de Farmacologia e Toxicologia Celular-LFTC/FarmaTec, Faculdade de 
      Farmacia, Universidade Federal de Goias, Goiania, GO, Brazil.
FAU - Batista, Aline Carvalho
AU  - Batista AC
AD  - Laboratorio de Patologia Bucal, Faculdade de Odontologia, Universidade Federal de 
      Goias, Goiania, GO, Brazil.
FAU - Vinhal, Daniela Cristina
AU  - Vinhal DC
AD  - Laboratorio de Quimica Farmaceutica Medicinal (LQFM), Faculdade de Farmacia, 
      Universidade Federal de Goias, Goiania, GO, Brazil.
FAU - Menegatti, Ricardo
AU  - Menegatti R
AD  - Laboratorio de Quimica Farmaceutica Medicinal (LQFM), Faculdade de Farmacia, 
      Universidade Federal de Goias, Goiania, GO, Brazil.
FAU - Valadares, Marize Campos
AU  - Valadares MC
AD  - Laboratorio de Farmacologia e Toxicologia Celular-LFTC/FarmaTec, Faculdade de 
      Farmacia, Universidade Federal de Goias, Goiania, GO, Brazil. Electronic address: 
      marizeufg@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20160426
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Irritants)
RN  - 0 (Sunscreening Agents)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Cattle
MH  - Cell Line, Transformed
MH  - Cell Survival/drug effects/physiology/radiation effects
MH  - Chickens
MH  - Cornea/*drug effects/physiology/radiation effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical/methods
MH  - Female
MH  - Hep G2 Cells
MH  - Humans
MH  - Irritants/administration & dosage/*toxicity
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mutagenicity Tests/methods
MH  - Random Allocation
MH  - Skin/*drug effects/metabolism/radiation effects
MH  - Sunscreening Agents/*toxicity
MH  - Ultraviolet Rays/adverse effects
OTO - NOTNLM
OT  - Alternative methods
OT  - Eye irritation
OT  - Genotoxicity
OT  - Heterocyclic derivative
OT  - Phototoxicity
OT  - Skin sensitization
EDAT- 2016/05/01 06:00
MHDA- 2017/05/13 06:00
CRDT- 2016/05/01 06:00
PHST- 2015/11/20 00:00 [received]
PHST- 2016/04/17 00:00 [revised]
PHST- 2016/04/25 00:00 [accepted]
PHST- 2016/05/01 06:00 [pubmed]
PHST- 2017/05/13 06:00 [medline]
PHST- 2016/05/01 06:00 [entrez]
AID - S0300-483X(16)30037-3 [pii]
AID - 10.1016/j.tox.2016.04.007 [doi]
PST - ppublish
SO  - Toxicology. 2017 Feb 1;376:83-93. doi: 10.1016/j.tox.2016.04.007. Epub 2016 Apr 
      26.