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

## TL;DR

This study finds that certain PAHs in children's toys can strongly activate a skin sensitization pathway, with mixtures showing increased risk.

## Contribution

First assessment of skin sensitization potential of specific PAHs in children's toys and their mixtures.

## Key findings

- B[k]F showed 34-fold higher pathway activation than B[a]P.
- PAH mixtures exhibited synergistic effects, except when composed solely of potent sensitizers.
- B[b]F, chrysene, and B[a]P were identified as significant sensitizers.

## Abstract

Children are particularly susceptible to environmental pollutants. This study assessed the skin sensitisation risk associated with polycyclic aromatic hydrocarbons (PAHs), prevalent in toys.

To evaluate the skin sensitisation potential of PAHs using the KeratinoSens assay.

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.

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.

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.

Our study evaluated the skin sensitisation risk of polycyclic aromatic hydrocarbons (PAHs) in toys, revealing that B[k]F, B[b]F and chrysene are highly potent sensitizers. Synergistic effects in PAH mixtures underscore the need to consider combined exposures when assessing environmental risks to children.