Abstract
First responders, particularly firefighters, are chronically exposed to carcinogens, including polycyclic aromatic hydrocarbons (PAHs) and per- and polyfluoroalkyl substances (PFAS), yet biological consequences, especially in female firefighters, remain undercharacterized. Traumatic brain injury (TBI), frequently encountered by first responders, lacks therapeutics deployable outside hospitals. This dissertation bridges both domains through exposure characterization, microbiome-integrated risk assessment, and nanotechnology-based neuroprotection.
A GC-MS method was developed to quantify 16 priority PAHs as unmetabolized parent compounds in firefighter urine across three cohorts. Fire-related activity was the dominant determinant of PAH internalization, with even a single fire call producing significant elevations, underscoring cumulative risk over a firefighting career. To extend this work, vaginal swabs from female firefighters were analyzed for PAHs, high-risk HPV, and microbial composition against community controls. Firefighters carried higher PAH burden, associated with HPV infection and dysbiosis implicated in cervical dysplasia, suggesting a pathway elevating reproductive cancer risk. In parallel, firefighting foam toxicity was evaluated in human kidney cells, with significant impairment of proliferation below operational concentrations tied to PFAS and surfactant composition.
To address TBI, drug nanoparticles were synthesized from vanilloid compounds with high stability and negligible cytotoxicity, and then delivered intranasally in a rodent model, producing rapid, localized brain cooling. Core temperature remained near baseline, demonstrating targeted, carrier-free nanodrug-induced hypothermia and a viable point-of-injury neuroprotective strategy.
This dissertation advances discovery and technologies for individuals working in high-risk occupational settings, characterizing multi-route carcinogen exposure in firefighters and establishing a nanodrug delivery platform for first responders treating TBI.