The Way Forward

Validated in vitro methods are available for skin irritation testing without animals for the hazard assessment of most agents within the EU. However, the total elimination of animals for skin irritation testing depends upon the acceptance of the validated in vitro methods by the regulatory authorities (Grindon, et al., 2007). Additionally, the assessment of reversibility and the dose response data needed for risk assessment for skin irritation cannot be totally replaced with the current validated in vitro methods (ECVAM, 2005). For these latter testing applications, additional refinement of the in vitro methods and their validation for the intended purposes needs to be completed.

In vitro methods for skin corrosion are sufficient for both hazard and risk assessment purposes in the EU and for many regulatory purposes in the US. Acceptance of in vitro data for skin corrosion depends upon the regulatory authority, and a case can usually be made for its acceptance.

A recent report by the Fund for the Replacement of Animals in Medical Experiments (FRAME) reviewed integrated testing strategies for skin corrosion and irritation, and proposed a decision-tree tiered testing scheme that could be used to eliminate animal use for skin testing in the EU REACH program (Grindon, et al., 2007). These scientists also identified the need for better in silico models for skin irritation/corrosion and for improving the predictivity of existing in vitro skin models. Some specific recommendations they made for in vitro skin models were:

• wider use of the IL-1α endpoint
• research to identify additional toxicity endpoints
• improved in vitro skin models, including co-culture models
• in vitro protocols for repeat dose testing and recovery

For more on The Way Forward, read the following invited commentary on skin irritation/corrosion toxicity testing:

• The Way Forward for In Vitro Skin Irritation Testing by Patrick Hayden