Frederick Jace
Skin sensitisation occurs when our skin comes into topical contact with something that causes an allergic adverse reaction. When a chemical allergen comes into contact with an individual’s skin, they may be susceptible to reactions that provoke a cutaneous immune response that can develop into contact sensitisation. For this reason, skin sensitisation prediction tests are carried out to identify the chemicals and contact times that are likely lead to an adverse effect, guided by use Adverse Outcome Pathway (AOP) assessment.
What is skin sensitisation, and why is it essential to test for it?
Skin sensitisation is an immune response that is both an environmental and occupational health issue, known to be a leading cause of occupational illnesses throughout the UK, USA and Europe. Therefore, skin sensitisation predictive testing must form a critical part of the testing carried out for any new drug, cosmetic or pesticide, including industrial sector chemicals.
Allergic contact dermatitis associated with considerable morbidities, and whilst not life-threatening, can undoubtedly be life-limiting. Allergic contact dermatitis and many allergic diseases progress in two phases. The first is a phase of induction which requires an allergen reactive T cell expansion in lymph nodes to drain the exposure site. The second phase, the elicitation phase, will only arise after repeated exposure to the sensitising material and leads to an allergic response whereby localised cutaneous inflammatory reactions occur.
The problems with skin sensitisation testing
For many years the only method available for skin sensitisation prediction involved in vivo testing, which involved animal or human patch testing, particularly in the cosmetics industry. The UK Government is again facing new calls to replace animal testing. . Not only because of the UK Government’s requirements on businesses to use fewer animals in testing as part of their commitments since 2011, but to meet the ever-growing pressure of consumers wanting products that are not tested on animals. Animal skin sensitisation models also have limited effectiveness in detecting human skin sensitisers, so a switch to using human based in vitro/in chemico methods may be more protective.
Such adversity to animal use has driven industries to find alternatives to bring new products to market. The ethical and political push has led to a greater understanding of the biology behind skin sensitisation and new testing methods emerging that work using fully validated in vitro testing to reach the same and even better conclusions. Testing methods such as those offered by Gentronix, experts in predictive toxicology, contribute to the provision of skin toxicology testing assays that enable comprehensive dermal toxicology assessments for a wide variety of industries.
Testing
In vitro assays enable each key event to be addressed within the associated OECD test guidelines. KE1-DPRA – direct peptide reactivity assay (OECD 442C), KE2-KeratinoSensTM (OECD 442D) and KE3- h-CLAT (OECD 442E), which combine to make a predictive testing strategy as part of the IATA (Integrated Approach to Testing and Assessment) that is readily available, reproducible and repeatable in the pursuit of reducing animal testing. When positive results are identified, expert advice can be sought to move forward. Such testing reduces the time and expenses involved in safely carrying out skin sensitisation testing and product development. The development of new agrochemicals, cosmetics, and the products for the medical and pharmaceutical sectors can now benefit from lower cost, consistent testing strategies that these assay tests provide to handle the critical events of skin sensitisation.
A quick conclusion
KE1 represents the molecular initiation binding the chemical with protein to form haptens. It may require oxidation (pre-hapten) or host enzyme activation (pro-hapten) to react with skin proteins.
KE2 is keratinocyte activation by a sensitiser to induce a localised inflammatory response and altered keratinocyte gene expression.
KE3 is the dendritic cell (DC) activation which requires a sensitising material to bind to maturation markers on dendritic cells enabling their interaction and activation of allergen reacting T cells within lymph nodes. This leads to T Cell proliferation defining KE4 and enables a prediction of a susceptible individual’s ability to become sensitised.
