Assessment of Human Skin Irritation:
Validation of In Vitro Models
May 2003
Executive Summary:
|
|
EpiDerm™ Skin Model
|
The worldwide drive to refine, reduce and/or replace animal-based testing of cosmetics and personal care products has accelerated and is quickly transitioning from "laudable goal" into validated studies targeted to the interests of the regulatory community in the United States and European Union.
This white paper summarizes the scientific findings from two recently published studies performed in support of the EU's efforts to validate reconstructed skin kits (in vitro skin models) as alternative methods for the assessment of several parameters, including human skin irritation [1] [2]. The 3 year project, 'Testing and Improvement of Reconstructed Skin Kits in Order to Elaborate European Standards', is a comprehensive multi-laboratory, multi-country project headed by L'Oreal (France), and including Beiersdorf (Germany), Wella Cosmital (Switzerland) and Leiden University (The Netherlands) sponsored by the European Union (EC DG XII). Importantly, there is precedence for data generated in EU (ECVAM) studies forming the core data set for submission to US regulators thru the ICCVAM process [3].
The project's purpose was to characterize several commercially available in vitro skin models with regard to tissue architecture and lipid composition, and to assess those models' utility in skin irritation, percutaneous absorption and metabolism studies. With regard to skin irritation, the major goals were to identify the in vitro test method endpoint(s) that best correlated in vitro test results to skin irritation symptoms observed in human subjects (best in vivo to in vitro correlation) and to identify the in vitro skin model(s) that demonstrated both high relevance and high reproducibility.
MatTek Corporation's EpiDerm™ human cell-derived, organotypic in vitro skin model was evaluated in both studies and performed exceedingly well in both. Key points from these studies as they relate to EpiDerm and the assessment of skin irritation include:
- Best Endpoint Relevance - The MTT ET-50 Tissue Viability Assay1 was found to be the most predictive endpoint for human skin irritation (the best in vivo to in vitro correlation).
- Best Skin Model Relevance - EpiDerm achieved the best in vivo to in vitro correlation of all of the in vitro skin models tested (R = 0.94). Ranking was based on MTT ET-50 Tissue Viability Assay.
- Best Skin Model Reproducibility - EpiDerm had the best intra-lot and inter-lot reproducibility (lowest coefficients of variation) of all the in vitro skin models tested, based on MTT ET-50 Tissue Viability Assay results.
To date, EpiDerm has been formally validated by European regulators [4], and proposed for formal acceptance by American regulators [3], as an alternative to animal testing for predicting the dermal corrosivity of new chemical and cosmetic formulations. EpiDerm is also performing superbly in ongoing phototoxicity validation testing.
EpiOcular™, another MatTek organotypic in vitro tissue model designed to assess ocular irritancy, is in the process of being formally validated as an alternative to the Draize Rabbit Eye Test. This effort is being sponsored by Colgate-Palmolive [5] via the ICCVAM [6] process in the United States. Colgate organized this formal multi-laboratory initiative with participation by 3M Corporation and Kimberly-Clark [7]. Avon Products recently presented EpiOcular-based research that established a reference database of in vitro ocular irritation scores for a cross-section of currently marketed cosmetic and personal care products [8]. Avon researchers also found that data generated using the EpiOcular model allowed them to distinguish differences in mild, milder and mildest ("sub-draize") formulations.
In Europe ECVAM has identified EpiOcular as a promising alternative approach for ocular irritation testing [5] with preliminary studies by ZEBET (Germany's Center for Documentation and Evaluation of Alternative Methods to Animal Experiments).
What do these study results mean to cosmetics and personal care product manufacturers, and to their ingredient suppliers? If they sell their products in the European Union, their Product Development/Product Safety Departments should be actively considering alternative toxicological test methods. They should also seek assurance that those alternative test methods are based on in vitro models that are either accepted by regulators, or are performing well in ongoing validation testing that meets regulatory criteria, such as MatTek's EpiDerm in vitro skin model and EpiOcular in vitro model for ocular irritation.
Latest Skin Irritation Measurement Information
To download a copy of the complete 11 page MatTek Skin Irritation Validation White Paper (PDF format), please click on the following link: "Skin Irritation White Paper".
====================
Footnote
1. MTT ET-50 Tissue Viability Assay: a quantitative method for evaluating a tissue's viability in response to external factors. ET-50: time of exposure for a test article to reduce tissue viability to 50%.
====================
References - Executive Summary Section
1. Faller, C. and Bracher, M. Reconstructed skin kits: reproducibility of cutaneous irritancy testing. Skin Pharmacology and Applied Skin Physiology 15 (Suppl 1) 74-91 (2002)
2. Faller, C., Bracher, M., Dami, N. and Roguet R. Predictive ability of reconstructed human epidermis equivalents for the assessment of skin irritation of cosmetics. Toxicology In Vitro 16, 557-572, (2002)
3. ICCVAM Evaluation of EPISKIN™, EpiDerm™ (EPI-200), and the Rat Skin Transcutaneous Electrical Resistance (TER) Assay: In Vitro Test Methods for Assessing Dermal Corrosivity Potential of Chemicals. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). NIH Publication 02-4502, June (2002)
4. Statement on the Application of the EpiDerm™ Human Skin Model for Skin Corrosivity Testing. ECVAM Scientific Advisory Committee (ESAC), European Centre for the Validation of Alternative Methods (ECVAM), March (2000)
5. Evaluating the ocular irritation potential of 54 test articles using the EpiOcular human tissue construct model (OCL-200). Blazka, M.E., Harbell, J.W., Klausner, M., Merrill, J., Kubilus, J., C Kloos, C., Bagley, D.M. Society of Toxicology Meeting, Poster # 1070 March (2003)
6. NIEHS (National Institute of Environmental Health Sciences), Validation and Regulatory Acceptance of Toxicological Test Methods: A Report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods, NIH Publication No. 97-3981, March (1997)
7. Blazka, M.E., Harbell, J.W., Klausner, M., Raabe, H., Kubilus, J., Hsia, F., Minerath, B., Bagley, D.M. Colgate-Palmolive's programme to validate the EpiOcular™ human tissue construct model (OCL-200). ATLA, 27, 331, (1999)
8. McCain, N.E., Binetti, R.R., Gettings, S.D., Jones, B.C. Assessment of ocular irritation ranges of market-leading cosmetic and personal-care products using an in vitro tissue equivalent. The Toxicologist, 66 (1-S), 243, Soc. of Toxicol. (Reston, VA), Abstract #1191, (2002)
|
