Toxicity evaluation of the photoprotective compound LQFM048: Eye irritation, skin toxicity and genotoxic endpoints

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• 作者：Renato Ivan de Á ; vila^a ; ¹ ; Marcelo de Sousa Vieira^a ; ¹ ; Marilisa Pedroso Nogueira Gaeti^b ; Larissa Cleres Moreira^a ; Laí ; s de Brito Rodrigues^a ; Gisele Augusto Rodrigues de Oliveira^a ; Aline Carvalho Batista^c ; Daniela Cristina Vinhal^d ; Ricardo Menegatti^d ; Marize Campos Valadares^a ; ^{marizeufg@gmail.com}
• 关键词：Alternative methods ; Eye irritation ; Genotoxicity ; Heterocyclic derivative ; Phototoxicity ; Skin sensitization
• 刊名：Toxicology
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：376
• 期：Complete
• 页码：83-93
• 全文大小：2018 K
• 卷排序：376

文摘

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.