Whether to support medical or cosmetic products, skin sensitization testing is vital in ensuring there are no ill effects on the person using them.
However, both regulatory requirements and welfare concerns have led to organizations seeking to test the skin sensitization of their products through other means.
Thankfully, due to advances in understanding the chemical and biological events that lead to sensitization, there has been much development into non-animal test methods for skin sensitization.
The question is, how far do these non-animal testing procedures go? Are there challenges involved, and how far are we from seeing an acceptance by the regulators of non-animal testing methods regarding skin sensitization?
We asked the experts Gentronix to further explain the non-animal skin sensitization tests available.
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There are, of course, some challenges inaccurate prediction when it comes to skin sensitization. Potency prediction appears to be one such challenge, although GARD (Genomic Allergen Rapid Detection) could prove helpful in some cases.
That said, there has been a good amount of progress in the in vitro and in chemical approaches when predicting hazards. Such tools could be used to replace or partly replace historically animal methods.
They could also help with labeling and classification requirements. A positive result may need to be followed up with a lymph node assay – that way, organizations will be able to discriminate between GHS categories 1A and 1B.
At the time of posting, there are six such non-animal related methods for in vitro assays, and these address the initial three key skin sensitization events. They are validated and have been formulated into internationally recognized OECD test guidelines.
There is currently only one test method validated, which has achieved acceptance in terms of the regulatory requirements for KE1. This is the direct peptide reactivity assay (DPRA) which is an in chemico test. It measures the binding to skin proteins of the AOP by utilizing model synthetic peptides.
Two in vitro test methods have obtained regulatory acceptance for KE2. These are LuSens and KeratinoSens. These methods reflect that sensitizers could induce genes regulated by the ARE (Antioxidant Response Element) in keratinocytes.
By measuring the Nrf2 mediated activations of ARE-dependant genes in derived keratinocyte human cell lines.
When it comes to KE3, there are three validated in vitro methods. The OECD’s methods include the IL-8 Luc Assay, the human Cell Line Activation Test, and U-SENS. These methods all measure the biomarkers relating to dendritic cell maturation.
There are some limitations to this testing, and when you add the complexity of skin sensitization at an underlying biology level, this means that no single assay will be enough to predict the potential of skin sensitization.
However, there is a general assumption that a combination of such methods could replace animal-based testing for skin sensitization.
Further to this, the belief is that data derived from these assays, which align to the initial three vital elements of skin sensitization AOP, should be combined with relevant data such as any structural alert and cross reading from chemical analogs.
This means there must be an integrated approach to the assessment and testing of skin sensitization in accordance with IATA.
When it comes to whether the current applications of non-animal testing methods are enough to achieve regulatory approval, this is still a challenge.
While significant advances continue to be made, the long-term goal is still some way off for making accurate skin sensitization predictions without the use of animal testing.