A new reconstructed human epidermis for in vitro skin irritation testing.
Different models of reconstructed human epidermis (RHE) are currently validated to assess skin irritation in vitro and ultimately to the animal replacement of the Draize test. The development of a new RHE model is a challenge for many laboratories, representing a potential gain of autonomy and improvement of technological knowledge. The Organization for Economic Co-operation and Development (OECD) encourages the development of new models and, for this purpose, offers a thorough guideline on quality control parameters (OECD TG 439 performance standards). This work aimed to develop an RHE model (i.e. USP-RHE) for in vitro skin irritation assays, following the OECD TG 439. The developed model presents a well-differentiated epidermis similar to the Validated Reference Methods (VRM) and to native human epidermis. Quality parameters, i.e. optical density of negative control, tissue integrity and barrier function, were similar to VRM and in accordance with OECD TG 439. Moreover, the USP-RHE model was shown to have 85,7% of specificity (6/7), 100% of sensitivity (6/6) and 92,3% of accuracy (12/13) when compared to in vivo UN GHS classification. The within-laboratory reproducibility was 92.3% (12/13). Thus, we demonstrated that USP-RHE model attends to all OECD TG 439 performance standards and is ready to be used by private and public laboratories and companies for future validation studies.
Clinical Chemistry & Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, Bloco 17, 05508-000 São Paulo, SP, Brazil.
Tatiana do Nascimento
TDN
Pedrosa
Clinical Chemistry & Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, Bloco 17, 05508-000 São Paulo, SP, Brazil.
Carolina Motter
CM
Catarino
Clinical Chemistry & Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, Bloco 17, 05508-000 São Paulo, SP, Brazil.
Paula Comune
PC
Pennacchi
Clinical Chemistry & Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, Bloco 17, 05508-000 São Paulo, SP, Brazil.
Sílvia Romano de
SR
Assis
Department of Clinical Analysis and Biomedicine, State University of Maringá, Avenida Colombo, 5790, CEP, 87020-900 Maringá, Paraná, Brazil.
Fabrícia
F
Gimenes
Department of Clinical Analysis and Biomedicine, State University of Maringá, Avenida Colombo, 5790, CEP, 87020-900 Maringá, Paraná, Brazil.
Márcia Edilaine Lopes
MEL
Consolaro
Clinical Chemistry & Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, Bloco 17, 05508-000 São Paulo, SP, Brazil.
Silvia Berlanga de Moraes
SBM
Barros
Clinical Chemistry & Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 580, Bloco 17, 05508-000 São Paulo, SP, Brazil. Electronic address: silvya@usp.br.
Silvya Stuchi
SS
Maria-Engler
D000826:Animal Testing Alternatives; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007509:Irritants / Q000633:toxicity*; D015603:Keratinocytes; D008954:Models, Biological; D023422:Skin Irritancy Tests
D007509:Irritants
Irritation assays; New skin models; OECD; RHE