What is Skin Sensitisation Testing?

Skin sensitisation resulting in allergic reactions and contact dermatitis, particularly in cosmetic or personal care products, is a fast-growing issue in the UK. In the area of occupational health, it is a fact that many productive hours are lost due to employees reacting badly to chemicals, where repeated or continual exposure to chemical agents can result in severe reactions.

In the case of occupational chemicals, it is thought that when a sensitising chemical compound achieves skin penetration and reaches the epidermis,  (sometimes requiring metabolic activation) it triggers the skin sensitisation process. In the case of cosmetics or personal care products, there is an immune reaction to exogenous reactive haptens, or pro haptens, which react with skin proteins. 

Skin sensitisation testing is used to determine if a chemical or other substance has the potential to cause an allergic reaction, such as allergic contact dermatitis (ACD), and toxicity testing is performed on any industrial chemical or cosmetic ingredient which can come into contact with skin.

A Potted History Of Skin Sensitisation Testing

Historically, the assessment of skin sensitivity has relied on animal testing, such as the local lymph node assay on mice (LLNA) or guinea pig testing, such as the maximisation and Buehler test. Whilst the LLNA is still the preferred assay to assess and predict skin sensitisation, animal testing is widely un-favoured by public opinion, and leading experts in predictive toxicology such as Gentronix are working hard to deliver innovative non-animal solutions for skin sensitisation and to deliver predictive toxicology products and services to global chemical sectors.

Skin sensitisation testing is essential for assessing the potential risks to human health of many industrial or domestic chemical or ingredient. It is compulsory in determining the safety or otherwise of consumer or industrial products. However, because of the ongoing debate around the ethics of animal testing, alternative methods such as in vitro and in-silico test models are increasingly being developed and validated.

How Does Testing Work?

When animals – usually a small test group of mice or guinea pigs – are used in skin sensitisation testing, they will have a small amount of the test substance applied to the skin. The animals are then observed for signs of irritation or inflammation of the skin test patch. The test substance may be applied multiple times to the same test subjects to acclimate the animals to the test substance. Eventually, the test substance will take a more concentrated form. Observations are taken multiple times to look for signs of any reaction – redness, swelling or itching – and if a reaction is seen, the test substance is considered a skin irritant.

In vitro and in chemico testing is typically performed with test substance dissolved in a solvent and applied to the peptides or cells of interest for assessing key steps of the adverse outcome pathway.

Stages Of ACD

The development of ACD following repeated exposure to a sensitising agent can be characterised in two separate stages, and they are:

  • Sensitisation, which is the induction of immunological memory triggered by the initial exposure
  • Elicitation, the appearance of the clinical allergic response following exposure to the allergen.

Understanding more about skin sensitisation 

The Adverse Outcome Pathway for Skin Sensitisation document is the globally accepted reference and understanding of the adverse outcome pathway (AOP) for skin sensitisation initiated by covalently binding to skin proteins. It identifies the key biological events* that underpin the sensitisation process and databases containing test results. AOPs can be incorporated into integrated testing and assessment approaches or chemical categories-based assessments.

*key events as specified in EU regulations which aim to protect human health and the environment include 

  • KE1 (haptenation)
  • KE2 release of pro-inflammatory cytokines
  • KE3 maturation and mobilisation of dendritic cells, immune-competent cells
  • KE4 antigen presentation to naïve T-cells and proliferation of memory T-cells