Optimised testing strategies for skin sensitization--the LLNA and beyond

Area of Science:

• Toxicology
• Dermatology
• In vitro testing

Background:

• The 21st-century toxicology field is shifting towards non-animal testing methods.
• Skin sensitization assessment is a key area for developing alternative methods.
• The widely used in vivo Local Lymph Node Assay (LLNA) has known limitations, including false positives and negatives.

Framework:

• Review of the LLNA's performance and limitations.
• Exploration of weight-of-evidence approaches for classification, labeling, and risk assessment.
• Assessment of the current status and progress of alternative testing strategies.

Implementation:

• Progress in developing in vitro methods for hazard identification, with some nearing validation.
• Recognition that (Quantitative) Structure-Activity Relationship ((Q)SAR) tools require further development for widespread practical use.
• Challenges remain in testing lipophilic substances and developing non-animal methods for potency assessment.

Implications:

• The findings support the transition towards validated non-animal methods for skin sensitization.
• Continued research and development are necessary to address remaining challenges in alternative toxicology.
• Enhanced risk assessment and regulatory compliance can be achieved through improved testing strategies.