PNNL

Abstract

One of the most significant challenges in environmental human health assessment is to evaluate hazards from exposure to environmental chemical mixtures. Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous contaminants typically found as mixtures in gaseous and particulate phases in ambient air pollution associated with petrochemicals from Superfund sites and burning of fossil fuels. However, little is understood about how PAHs in mixtures contribute to toxicity in lung cells. To investigate mixture interactions and component additivity from environmentally relevant PAHs, two synthetic mixtures were created from PAHs identified in passive air samplers at a legacy creosote site impacted by wildfires. Primary human bronchial epithelial cells differentiated at the air liquid interface (ALI-HBECs) were treated with PAH mixtures at environmentally relevant proportions and evaluated for differential expression of transcriptional biomarkers related to xenobiotic metabolism, oxidative stress response, barrier integrity, and DNA damage response by qPCR. Results were utilized in two Independent Action (IA) models to evaluate the mixture response. Both IA models exhibited trends that were unlike the observed mixture response trend suggesting possible interactions and similar or mostly similar mechanisms of action between the mixture components. Overall, this study provides an example of mixture toxicity assessment with currently available methods and evidence for the interpretability and usefulness of mixture toxicity assessments. In addition, these data demonstrate the need for more complex yet interpretable mixture response evaluation methods.