With the advent of globalization and human innovation, new products made of various materials are available in the market. The materials these products are composed from could be of natural origin or synthetic with a possibility of posing detrimental effects to human health during usage. The first organ that comes in contact with any product used is the human skin making it the most susceptible tissue to possible harm. Any chemical or material which has a potential to elicit an allergic reaction on the skin is categorized as a skin-sensitizer otherwise, a non-sensitizer. The ultimate purpose of testing a product for possible skin sensitivity is to ensure safety of the end-user.
Foreseeing the likelihood of certain chemicals or materials used in products posing risk to end-user, the regulatory bodies proposed a requirement for manufacturers to have their products tested for presence of skin-sensitizers. Owing to the increasing presence of skin-sensitizers in products, skin sensitization test became a regulatory requirement in many countries. The Organization for Economic Cooperation and Development (OECD) came up with internationally agreed collection of guidelines for testing chemicals used by governments, industries, and independent laboratories to assess the safety of chemicals.
Pertaining to skin sensitization, OECD identified an Adverse Outcome Pathway (AOP) of four major key events (KE) leading to allergic contact dermatitis (ACD, a clinical outcome caused by exposure to skin sensitizers –
KE1: Covalent binding of the chemical with the surface of the skin
KE2: Release of cytokines and other pro-inflammatory factors in keratinocytes
KE3: Maturation and mobilization of dendritic cells
KE4: Antigen presentation to new T-cells and proliferation of memory T-cells
The KE3 is an important key biological event in which dendritic cells and other immunocompetent cells in the skin get activated with an increased expression of cell membrane markers and proinflammatory cytokines indicating cellular level immune response upon exposure to a skin-sensitizer. Of the test methods recognized by OECD addressing mechanisms under KE3 (OECD TG 442E), the GARD®skin (Genomic Allergen Rapid Detection) assay stands apart with its holistic approach in mimicking the human immune response following exposure to skin sensitizers.
The GARD®skin consists of biomarker signatures representing genes with known or relevant biological function which are part of the OECD defined KEs and also, mimic human immune response. GARD®skin redefined skin sensitization testing with state-of-the-art genomic and machine learning techniques to elaborate on pathway analysis of its biomarker signatures. In a single test, this multi-mechanistic in vitro assay identifies and measures genes responsible for –
1. Oxidative stress responses
2. Inflammasome complex formation
3. Pro-inflammatory cytokine and chemokine signalling, and dendritic cell activation and maturation
4. Pattern recognition receptors, heat shock proteins, and mitogen-activated protein kinase (MAPK) activation
5. Immunological self-defence mechanisms
6. Cell migration
7. Innate immune system activation and xenobiotic recognition
The GARD® technology platform is based on chemical stimulation and the analysis of relative expression levels of genomic biomarker signatures. It is comprised of four key elements:
1. SenzaCellTM: The first key element is the biological cell system called SenzaCellTM that mimics the human dendritic cells (a critical part of the human immune system that recognize allergens).
2. Training dataset: Training dataset of gene expression profiles from cellular exposures to a set of well-characterized chemical sensitizers and non-sensitizers is the second key element.
3. Genomic biomarker signature: By analysing the training dataset of relevant genes, a genomic biomarker signature is established.
4. Prediction model: Based on the gene expression patterns obtained from the genomic biomarker signature, machine-learning technology is used to create prediction models for the investigated endpoint. The predicted models are used to classify test chemicals in future.
With increasing interest in application of genomics and data processing techniques to interpret and understand skin sensitization, we are progressing towards accepting next-generation test models like GARD®skin as potential standalone tests. Embracing such testing protocols allows companies to stand out in the market and build lasting consumer trust by creating a safer tomorrow for all.
For most products from various industries including cosmetics, textiles, agrochemical and medical devices exported to the European Union (EU) regardless of the amount, skin sensitization evaluation is a mandatory regulatory requirement. Prioritizing skin sensitization ensures wellbeing of consumers and elevates a product’s safety.
GV Research Platform (GVRP) can help you elevate your product safety with GARD®skin technology being the authorized distributor of SenzaGen’s services in India. Unlock a wide range of skin sensitization testing services and add-ons by enrolling your products for GARD®skin sensitization testing services.
Sai Supriya has a 2 year experience in academic research and fair exposure to transition into industry. She enjoys delving deep into the new developments in the biotech, pharma industry and collaborating with people. She is zealous and keen to direct her best strengths to the role by being receptive to new ideas and challenges.