Arachidonic acid release: an in vitro alternative for dermal irritancy testing

Area of Science:

• Toxicology
• In vitro testing
• Dermal irritation

Background:

• Validated in vitro alternatives exist for mutagenicity and ocular irritancy, but dermal irritancy assays lag.
• Human skin's irritant response involves eicosanoids derived from arachidonic acid.

Purpose of the Study:

• To investigate the release of [3H]arachidonic acid from cultured murine fibroblasts (C3H-10T1/2 cells) in response to anionic surfactants (AS) and finished products (FP).
• To establish a novel, mechanistically based in vitro screen for dermal irritancy testing.

Main Methods:

• Murine fibroblast cell lines were exposed to non-lethal concentrations of AS and FP.
• Statistical methods standardized results by comparing test substance responses to a positive control (sodium dodecyl sulfate - SDS).
• Relative potencies were calculated and correlated with in vivo dermal irritation indices from rabbit studies.

Main Results:

• The in vitro assay demonstrated significant correlations with in vivo dermal irritation data, particularly for pure anionic surfactants.
• Excluding certain finished products (extreme pH or insoluble) improved the overall in vivo-in vitro correlation.
• The release of [3H]arachidonic acid from cultured skin cells proved to be a reliable indicator of dermal irritancy.

Conclusions:

• The release of [3H]arachidonic acid from cultured skin cells offers a novel, mechanistically based in vitro screen for dermal irritancy.
• This method shows potential for reducing animal testing in dermal irritation assessments.
• Further refinement could lead to a widely applicable alternative assay for predicting skin irritation.