The dermal sensitization threshold (DST) approach for mixtures evaluated as negative in in vitro test methods;...

Area of Science:

• Cosmetic science
• Toxicology
• Dermal exposure assessment

Background:

• Cosmetic ingredients, like botanical extracts, can be complex mixtures containing skin sensitizers.
• Previous in vitro test batteries (KeratinoSens™ and h-CLAT) showed lower sensitivity for some sensitizers compared to murine local lymph node assays (LLNA).
• Uncertainty arises from decreased sensitivity in in vitro methods for certain sensitizers in mixtures.

Purpose of the Study:

• To develop a risk assessment strategy for cosmetic ingredient mixtures with negative results from in vitro test batteries.
• To minimize uncertainty associated with the reduced sensitivity of in vitro methods for specific sensitizers.
• To establish a reliable dermal sensitization threshold for mixtures (mixture DST).

Main Methods:

• A risk assessment strategy was developed assuming a no expected sensitization induction level of mixtures (mixture NESIL) for mixtures with negative in vitro results.
• 146 sensitizers were assessed using in vitro and LLNA data, considering the assumption of indeterminate constituents in mixtures.
• Calculated 95th percentile probabilities of mixture NESILs to derive the mixture DST.

Main Results:

• A mixture DST of 6010 μg/cm² was derived for mixtures yielding negative results in the binary in vitro test battery.
• The developed approach was found to be practical for risk assessments in the cosmetic industry.
• Feasibility studies confirmed the utility of the proposed risk assessment strategy.

Conclusions:

• The novel risk assessment strategy effectively incorporates the DST approach and in vitro test data.
• This method provides a robust framework for evaluating the dermal sensitization potential of cosmetic ingredient mixtures.
• The strategy enhances the reliability of risk assessments for cosmetic products containing complex mixtures.