Purpose: We developed a glutathione-containing screening (GCS) system capable of confirming toxicity at the substance screening stage aimed at reducing the time and cost of the cosmetic raw material development stage. Methods: Based on genotoxicity testing, a GCS system, comprising a direct and indirect system, was developed to reduce the time and cost to identify toxicity during the screening of candidate cosmetic substances. Toxicity potential was confirmed by identifying changes in the content of total glutathione (GSH), which conjugates only toxic substances, and those in the glutathione disulfide (GSSG)/GSH ratio. Results: Heptanal, a positive control substance in skin irritation tests, showed a decrease in total GSH and was identified as a direct-acting toxicant. Eugenol, a positive control substance in skin sensitization tests, showed a decrease in total GSH and an altered GSSG/GSH ratio and was identified as an indirect-acting toxicant. Conclusion: The GCS system could identify toxicity characteristics of skin irritation and sensitization. However, more positive chemicals are required to induce skin irritation or sensitization to challenge a chemical's toxic classification such as irritation or sensitization according to the GCS system, direct and indirect systems.
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