Assessing the acute toxicity of photodegraded anthracene with in vitro and in vivo skin models

The Gulf Coast of Texas is heavily inundated with petroleum refineries that release Polycyclic Aromatic Hydrocarbons (PAHs) into nearby waters, and these chemicals may pose a threat to human health when they interact with environmental conditions. PAHs are a group of hundreds of different chemicals, and the Environmental Protection Agency has identified 16 priority PAHs. Many of these chemicals are acute skin irritants and can cause skin, lung, bladder, and liver cancer with chronic exposure. Humans can be exposed when they interact with contaminated air, soil, and water. Recent studies have demonstrated that abiotic factors such as UV light, salinity, and pH can modify PAH structure, however, it is unknown how these modifications affect acute toxicity to the human skin barrier. The objectives of this study were to characterize the phototoxic effects of a priority PAH, anthracene by testing photodegradation treatments on cell culture and animal models. Gas chromatography and mass-spectroscopy confirmed the presence of 1,9-anthraquinone and phthalic acid, both known skin irritants, in photodegradation products. Keratinocyte cell culture was used to assess the impacts of photodegraded anthracene on cell migration, viability, and stratification development. We found that longer photodegradation times resulted in decreased cell viability and increased migration. A unique three-dimensional stratification assay demonstrated that photodegraded anthracene reduces differentiation in apical keratinocytes. Relative gene expression analysis suggests that keratinocytes bypass TLR-4 activation and utilize IL-1?, IL-1?, and TNF-? to produce an inflammatory response. Mus musculus studies indicate that extracellular matrix remodeling may be induced by 4, 8, and 24-hour photodegraded intermediates by keratinocyte-derived Il-1?, S100a9, Mmp1, and Connexin43. The results of this study indicate that photodegradation can produce intermediates that may elicit dermal inflammation, and the presence of these intermediates should be evaluated in bays with high foot-traffic.