Topical exposure to chemicals can lead to adverse skin effects. According to the severity and reversibility of effects one distinguishes skin corrosion (=skin burns) from skin irritation.
Corrosive substances irreversibly damage the skin beyond repair, while irritant substances lead to a reversible local inflammatory reaction caused by the innate (non-specific) immune system of the affected tissue: in response to chemically-induced tissue trauma and cell damage, skin cells release inflammatory mediators (chimokines and cytokines) which increase the diameter and permeability of blood vessels, attract immune cells (e.g. mast cells, neutrophiles) to the site of injury and trigger the migration of immune cells through the endothelium into the tissue where they participate in antigen clearance and tissue repair.
Moreover inflammatory mediators stimulate nerve endings leading to itching and stinging sensations.
Regulatory context and legislation
While some chemicals will only trigger an irritant response after repeated exposure of the same skin area (=cumulative irritants), other chemicalscause irritation even after a one-time exposure (=acute irritants).
Current regulatory requirements focus on the assessment of the acute irritation potential of chemicals in order to support the risk management associated with the handling and transport of chemicals, but also possible exposure to acutely irritant substances contained in various products.
Data on skin irritation effects are required by several pieces of legislations, notably:
- the Cosmetics Directive (76/768/EEC, which will be repealed, from July 2013 onwards, by the EU regulation on cosmetics products (EC 1223/2009)
- the Classification, Labelling and Packaging (CLP) Regulation (1272/2008)
- the REACH Regulation (1907/2006)
Currently, internationally accepted test methods for skin irritation testing include the traditional in vivo animal test (Draize rabbit test) as well as in vitro test methods (Table 1).
All accepted in vitro test methods are based on on human keratinocytes (the Reconstructed human Epidermis or RhE) validated by ECVAM. These keratonicytes, during culturing, form a multi-layered epidermis including a stratum corneum at the top, functioning as a barrier.
The following test methods have achieved regulatory acceptance:
- In vivo Draize rabbit test for skin corrosion/irritation testing: OECD test guideline 404
- In vitro skin irritation tests based on reconstructed human skin (EpiSkin, EpiDerm, SkinEthic): OECD test guideline 439 [/collapse]
EURL ECVAM validated test methods
The following methods have been validated by EURL ECVAM:
- EpiSkin Skin Irritation Test (SIT)
- EpiDerm Skin Irritation Test (SIT)
- SkinEthic Skin Irritation test (SIT)
- epiCS Skin Irritation Test (SIT)[/collapse]
Test methods under validation by EURL ECVAM
There are currently no test methods for in vitro skin irritation testing under validation at EURL ECVAM
However, EURL ECVAM continues to receive submissions of external test method validation studies performed in reference to the EURL ECVAM performance standards.
These submissions are evaluated by EURL ECVAM and, if found compliant with the performance standards, will be forwarded for ESAC peer review.[/collapse]
Development and optimisation of alternative methods
EURL ECVAM has been the lead organisation for the drafting and regulatory acceptance of TG 439 on in vitro skin irritation and is continuing activities in collaboration with the OECD test guidelines programme in view of improving the scientific use of in vitro skin irritation test methods, their standardisation but also their evaluation and validation.
The latter concerns at present predominantly so-called me-too methods i.e. test methods that are similar to the methods validated by ECVAM in 2007 and which were used to define the Performance Standards of in vitro skin irritation testing.
EURL ECVAM is regularly collaborating with OECD on updates of TG 439 in view of integrating recently validated and accepted test methods for in vitro skin irritation test method into this test guideline.
In addition, EURL ECVAM experts are participating in the OECD expert group on skin corrosion / irritation and have recently (2012-2013) been involved in the development of guidance on Integrated Approaches to Testing and Assessment (IATA) for skin irritation and skin corrosion testing.
The IATA builds on the Integrated Testing Strategy for skin corrosion/irritation testing originally developed for the EU REACH legislation under the coordination of ECVAM (2006-2007), but provides more prescriptive guidance based on additional data and experiences that became available in the past seven years.[/collapse]