Exploring the Activation of the Keap1-Nrf2-ARE Pathway by PAHs in Children's Toys

Lauenstein J, van de Weyer S, Alsaleh R, Wiedmer C, Büttner A, Kersch C, Schmitz-Spanke S (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Contact Dermatitis Wiley-Blackwell

DOI: 10.1111/cod.14792

Abstract

Background: Children are particularly susceptible to environmental pollutants. This study assessed the skin sensitisation risk associated with polycyclic aromatic hydrocarbons (PAHs), prevalent in toys. Objectives: To evaluate the skin sensitisation potential of PAHs using the KeratinoSens assay. Methods: Individual PAHs (acenaphthylene, anthracene, benzo[a]anthracene, benzo[a]pyrene (B[a]P), benzo[b]fluoranthene (B[b]F), benzo[e]pyrene, benzo[g,h,i]perylene, benzo[k]fluoranthene (B[k]F), chrysene, fluoranthene, fluorene, naphthalene, phenanthrene, pyrene and triphenylene) and ternary mixtures containing B[a]P were assessed for their ability to activate the Keap1-Nrf2-ARE pathway in human keratinocytes. The concentration addition model and additive index were used to predict and analyse mixture effects. Results: Among the individual PAHs, B[k]F demonstrated the most potent activation of the pathway, exhibiting a 34-fold higher potency relative to B[a]P. B[b]F, chrysene and B[a]P also exhibited significant activation, while the remaining PAHs displayed negligible or weak activation. Notably, PAH mixtures exhibited synergistic effects, except for those composed solely of potent sensitizers. Conclusions: This study provides the first assessment of the skin sensitization potential of these PAHs. The findings suggest that B[k]F, B[b]F and chrysene may pose a higher risk of skin sensitisation than previously thought. Additionally, the synergistic effects observed in mixtures highlight the importance of considering combined exposures when assessing PAH exposure risk.

Authors with CRIS profile

Jonas Lauenstein Department of Anaesthesiology Rasha Alsaleh Professur für Biomarker in der Arbeitsmedizin Andrea Büttner Lehrstuhl für Aroma- und Geruchsforschung Christian Kersch Lehrstuhl für Arbeits-, Sozial- und Umweltmedizin Simone Schmitz-Spanke Professur für Biomarker in der Arbeitsmedizin

Involved external institutions

Hochschule Anhalt DE Germany (DE)

How to cite

APA:

Lauenstein, J., van de Weyer, S., Alsaleh, R., Wiedmer, C., Büttner, A., Kersch, C., & Schmitz-Spanke, S. (2025). Exploring the Activation of the Keap1-Nrf2-ARE Pathway by PAHs in Children's Toys. Contact Dermatitis. https://doi.org/10.1111/cod.14792

MLA:

Lauenstein, Jonas, et al. "Exploring the Activation of the Keap1-Nrf2-ARE Pathway by PAHs in Children's Toys." Contact Dermatitis (2025).

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