Journal article
A new alternative method for testing skin irritation using a human skin model: a pilot study.
- Miles A Dermatology Clinic, Canton Vaud University Hospital (CHUV), Lausanne, Switzerland.
- Berthet A Institute of Work and Health (IST), University of Lausanne and Geneva, Lausanne, Switzerland.
- Hopf NB Institute of Work and Health (IST), University of Lausanne and Geneva, Lausanne, Switzerland.
- Gilliet M Dermatology Clinic, Canton Vaud University Hospital (CHUV), Lausanne, Switzerland.
- Raffoul W Reconstructive and Plastic Surgery Clinic, Canton Vaud University Hospital (CHUV), Lausanne, Switzerland.
- Vernez D Institute of Work and Health (IST), University of Lausanne and Geneva, Lausanne, Switzerland.
- Spring P Dermatology Clinic, Canton Vaud University Hospital (CHUV), Lausanne, Switzerland. Electronic address: Philipp.Spring@chuv.ch.
- 2013-11-12
Published in:
- Toxicology in vitro : an international journal published in association with BIBRA. - 2014
1-Bromohexane
Bentazon
Butylmethacrylate
DEHP
Draize test
Epiderm®
Episkin®
Folpet
Heptylbutyrate
Hexylsalicylate
Irritation scale
Isoproturon
Methylchloroisothiazolinone (MCI/MI)
Methylisothiazolinone (MI)
NaCl
Sodiumlaurylsulfate
Adult
False Negative Reactions
False Positive Reactions
Female
Humans
In Vitro Techniques
Irritants
Middle Aged
Models, Biological
Necrosis
Pilot Projects
Skin
Skin Diseases
Skin Irritancy Tests
Vacuoles
English
BACKGROUND
Studies assessing skin irritation to chemicals have traditionally used laboratory animals; however, such methods are questionable regarding their relevance for humans. New in vitro methods have been validated, such as the reconstructed human epidermis (RHE) model (Episkin®, Epiderm®). The comparison (accuracy) with in vivo results such as the 4-h human patch test (HPT) is 76% at best (Epiderm®). There is a need to develop an in vitro method that better simulates the anatomo-pathological changes encountered in vivo.
OBJECTIVES
To develop an in vitro method to determine skin irritation using human viable skin through histopathology, and compare the results of 4 tested substances to the main in vitro methods and in vivo animal method (Draize test).
METHODOLOGY
Human skin removed during surgery was dermatomed and mounted on an in vitro flow-through diffusion cell system. Ten chemicals with known non-irritant (heptylbutyrate, hexylsalicylate, butylmethacrylate, isoproturon, bentazon, DEHP and methylisothiazolinone (MI)) and irritant properties (folpet, 1-bromohexane and methylchloroisothiazolinone (MCI/MI)), a negative control (sodiumchloride) and a positive control (sodiumlaurylsulphate) were applied. The skin was exposed at least for 4h. Histopathology was performed to investigate irritation signs (spongiosis, necrosis, vacuolization).
RESULTS
We obtained 100% accuracy with the HPT model; 75% with the RHE models and 50% with the Draize test for 4 tested substances. The coefficients of variation (CV) between our three test batches were <0.1, showing good reproducibility. Furthermore, we reported objectively histopathological irritation signs (irritation scale): strong (folpet), significant (1-bromohexane), slight (MCI/MI at 750/250ppm) and none (isoproturon, bentazon, DEHP and MI).
CONCLUSIONS
This new in vitro test method presented effective results for the tested chemicals. It should be further validated using a greater number of substances; and tested in different laboratories in order to suitably evaluate reproducibility.
Studies assessing skin irritation to chemicals have traditionally used laboratory animals; however, such methods are questionable regarding their relevance for humans. New in vitro methods have been validated, such as the reconstructed human epidermis (RHE) model (Episkin®, Epiderm®). The comparison (accuracy) with in vivo results such as the 4-h human patch test (HPT) is 76% at best (Epiderm®). There is a need to develop an in vitro method that better simulates the anatomo-pathological changes encountered in vivo.
OBJECTIVES
To develop an in vitro method to determine skin irritation using human viable skin through histopathology, and compare the results of 4 tested substances to the main in vitro methods and in vivo animal method (Draize test).
METHODOLOGY
Human skin removed during surgery was dermatomed and mounted on an in vitro flow-through diffusion cell system. Ten chemicals with known non-irritant (heptylbutyrate, hexylsalicylate, butylmethacrylate, isoproturon, bentazon, DEHP and methylisothiazolinone (MI)) and irritant properties (folpet, 1-bromohexane and methylchloroisothiazolinone (MCI/MI)), a negative control (sodiumchloride) and a positive control (sodiumlaurylsulphate) were applied. The skin was exposed at least for 4h. Histopathology was performed to investigate irritation signs (spongiosis, necrosis, vacuolization).
RESULTS
We obtained 100% accuracy with the HPT model; 75% with the RHE models and 50% with the Draize test for 4 tested substances. The coefficients of variation (CV) between our three test batches were <0.1, showing good reproducibility. Furthermore, we reported objectively histopathological irritation signs (irritation scale): strong (folpet), significant (1-bromohexane), slight (MCI/MI at 750/250ppm) and none (isoproturon, bentazon, DEHP and MI).
CONCLUSIONS
This new in vitro test method presented effective results for the tested chemicals. It should be further validated using a greater number of substances; and tested in different laboratories in order to suitably evaluate reproducibility.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.tiv.2013.10.022
- PMID 24211334
- Persistent URL
- https://sonar.ch/global/documents/20166
Statistics
Document views: 25
File downloads: