Modeling PAH Mixture Interactions in a Human In Vitro Organotypic Respiratory Model.

One of the most significant challenges in human health risk 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 the 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. The primary human bronchial epithelial cells differentiated at the air-liquid interface were treated with PAH mixtures at environmentally relevant proportions and evaluated for the differential expression of transcriptional biomarkers related to xenobiotic metabolism, oxidative stress response, barrier integrity, and DNA damage response. Component additivity was evaluated across all endpoints using two independent action (IA) models with and without the scaling of components by toxic equivalence factors. Both IA models exhibited trends that were unlike the observed mixture response and generally underestimated the toxicity across dose suggesting the potential for non-additive interactions of components. Overall, this study provides an example of the usefulness of mixture toxicity assessment with the currently available methods while demonstrating the need for more complex yet interpretable mixture response evaluation methods for environmental samples.

The chemistry and toxicology of vaping.

Vaping is the process of inhaling and exhaling an aerosol produced by an e-cigarette, vape pen, or personal aerosolizer. When the device contains nicotine, the Food and Drug Administration (FDA) lists the product as an electronic nicotine delivery system or ENDS device. Similar electronic devices can be used to vape cannabis extracts. Over the past decade, the vaping market has increased exponentially, raising health concerns over the number of people exposed and a nationwide outbreak of cases of severe, sometimes fatal, lung dysfunction that arose suddenly in otherwise healthy individuals. In this review, we discuss the various vaping technologies, which are remarkably diverse, and summarize the use prevalence in the U.S. over time by youths and adults. We examine the complex chemistry of vape carrier solvents, flavoring chemicals, and transformation products. We review the health effects from epidemiological and laboratory studies and, finally, discuss the proposed mechanisms underlying some of these health effects. We conclude that since much of the research in this area is recent and vaping technologies are dynamic, our understanding of the health effects is insufficient. With the rapid growth of ENDS use, consumers and regulatory bodies need a better understanding of constituent-dependent toxicity to guide product use and regulatory decisions.