The skin is the largest organ of the body and it provides an efficient barrier regulating the movement of water and electrolytes (Elias, 2006), essential for maintaining overall homeostasis.
Moreover, the skin barrier protects the body against potentially harmful stimuli, e.g. exposure to antigens, ultraviolet light, microorganisms, toxins, small particles. In addition to such natural and potentially noxious stimuli, the skin may be exposed to a wide range of chemicals, i.e. through occupational exposure or consumer products (e.g. solvents, detergents).
Local (=topical) exposure to chemicals can lead to adverse effects on the skin. The extent of severity and reversibility of effects distinguishes skin irritation from skin corrosion (=skin burns).
Irritant substances lead to a reversible local inflammatory reaction caused by the innate (non-specific) immune system of the affected tissue, while corrosive substances irreversibly damage the skin through the epidermis and into the dermis, beyond repair. As a consequence, the affected area can be regenerated only from the healthy skin surrounding the necrotic1 patch.
According to the OECD Test Guideline 431 on "In vitro Skin Corrosion: Human Skin Model Test", skin corrosion is further defined as the production of irreversible damage of the skin; namely, visible necrosis through the epidermis and into the dermis, following the application of a test substance for up to four hours.
Corrosive reactions include ulcers, bleeding, bloody scabs, and, by the end of observation at 14 days (in an animal experiment), discoloration due to blanching of the skin, complete areas of alopecia, and scars.
Corrosivity is not a risk factor that usually occurs with cosmetics, but could occasionally arise after a manufacturing error or misuse by the consumer. However, a cosmetic ingredient that has the intrinsic property to be corrosive is not necessarily excluded for use in cosmetics.
It is very much depending on its final concentration in the cosmetic product, the presence of “neutralising” substances, the excipients used, the exposure route, the conditions of use, the amounts applied, etc. (Zuang et al., 2005).
Because chemicals may pose even severe risks, there is the need to have data on skin corrosivity potential in order to ensure a high level of protection to human health and occupational safety with the goal of achieving sustainable development while enhancing competitiveness and innovation.
1Necrosis is the death of cells through injury or disease, especially in a localised area of a tissue organ.
Regulatory context and Legislation
[collapsed]Data on skin irritation/corrosion effects are required by several pieces of legislation, notably:
- the Classification, Labelling and Packaging (CLP) Regulation (1272/2008)
- the EU regulation on cosmetic products (EC 1223/2009)
- the REACH Regulation (1907/2006)
The EU CLP Regulation implements the UN Globally Harmonized System (GHS) for classification and labelling (C&L). The C&L categories for skin corrosion and irritation are based on visually observable effects on live rabbit skin following exposure (Draize skin corrosion test).
Corrosive substances are labelled 'Category 1'. This category contains three optional subcategories which correspond to the UN Packing Groups I, II and III for the transport of goods. The subcategories are implemented in the EU. They differ with regard to the exposure times required to elicit skin corrosion in the rabbit and are referred to as 1A ("strong corrosive"), 1B ("moderate corrosive") and 1C ("mild corrosive").
Currently, internationally accepted test methods for skin corrosion testing include the traditional animal test (Draize rabbit test) as well as in vitro test methods, including test methods based on reconstructed human epidermis technology (RhE) validated by EURL ECVAM. RhE models use normal (e.g. non-transformed) human keratinocytes that, during culturing, form a multi-layered epidermis including a stratum corneum at the top, functioning as a barrier.
The same RhE test methods, however using a different exposure protocol, are employed for skin corrosion testing. In addition, alternative methods for skin corrosion include the Transcutaneous Electrial Resistance (TER) assay, based on excised animal skin and the Corrositex assay, based on an in vitro protein matrix.
The following test methods have gained international regulatory acceptance:
- In vivo Draize rabbit test for skin corrosion/irritation testing (OECD, TG 404)
- In vitro Transcutaneous Electrical Rrsistance test, TER (OECD, TG 430)
- Reconstructed human skin models, EpiSkin, EpiDerm, SkinEthic, EpiCS (OECD, TG 431)
- Corrositex (OECD, TG 435)[/collapse]
EURL ECVAM validated test methods
The following alternative test methods have been validated by EURL ECVAM:
|OECD TG 430||Rat Transcutaneous Electrical Resistance (TER) test|
|OECD TG 431|
|OECD TG 435|
Test methods under validation by EURL ECVAM
There are currently no methods for skin corrosion under validation by EURL ECVAM.[/collapse]
Development and optimisation of alternative methods
[collapsed]Having validated all current RHE-based in vitro skin corrosion (Fentem et al., 1998; Barratt et al., 1998), EURL ECVAM is continuing to follow the development of this area with respect to new technologies, assays and emerging concepts of production of reconstructed tissues.
EURL ECVAM is actively contributing with its expertise to international projects aiming at the further improvement of current available alternative methods for skin corrosion and irritation.
During the recent past most efforts regarding the update and further improvement of test methods for regulatory use have taken place within an OECD expert group on skin corrosion and irritation bringing together scientists from various OECD member countries, regulators, test method developers as well as validation experts.[/collapse]