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

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.