Climate change is increasing the risk of wildfires which frequently extend into the wildland-urban interface (WUI).WUI fires burn a mixture of vegetation structures and vehicles and there is a marked research gap regardingpopulation exposures and health effects. Woodsmoke contains a toxic mixture of known and suspectcarcinogens including but not limited to benzene aldehydes and polycyclic aromatic hydrocarbons (PAHs).However wildland fire exposure monitoring has generally been limited to particulates for the general public andPAHs for firefighters. Firefighters a high exposure group are requesting participatory research to measure WUIfire exposures and effects and identify effective interventions. Silicone wrist bands can measure exposurebeyond PAHs and urine metabolomics can identify both exposures and effects. While cancer or other diseasescaused by firefighting exposures can take many years to develop metabolomic and epigenetic (microRNA andDNA methylation) endpoints can serve as sub-clinical biomarkers of toxicity. Interventions of firefighter interestinclude rapid provision of exposure data improved personal protective equipment (PPE) more rapid dermaldecontamination and administrative controls. We hypothesize that: a) use of silicone wristbands and targetedurinary analyses (hydroxylated PAHs) will identify high-exposure settings and activities and that untargetedmetabolomics will reveal novel environmental compounds of concern; b) the urine metabolome and microRNAswill change acutely with exposures and cumulative exposures will be associated with long-term DNA methylationchanges in firefighters; and c) interventions chosen by firefighters will significantly reduce exposures. We willtest these hypotheses through evaluating firefighter exposures during WUI responses measuring toxic effectsand evaluating interventions to reduce exposures. Our fire service research champions have enrolled LosAngeles County and Orange County firefighters who could respond to WUI fires in the Fire Fighter Cancer CohortStudy (FFCCS) a fire service-academic community-engaged research collaborative. For the proposed researchwe will measure exposures of firefighters during WUI responses using silicone wristbands and pre- and post-exposure urine for targeted (hydroxylated PAHs) and untargeted (metabolomics) analyses. Occupationalfireground characteristics (type of fire PPE time at fire activities) will be recorded. Using urine and bloodcollected at baseline and post-exposure we will evaluate acute effects with changes in endogenous metabolites(pre/post urine) and microRNA (pre/post blood). Longer-term changes in DNA methylation will be evaluatedcomparing baseline blood samples to three years afterwards. Exposure reduction interventions selected by thefire service will be evaluated comparing intervention and activity control groups with pre- and post-exposurewristband and urinary PAH metabolite measurements. We anticipate that the proposed research will provide amore complete measure of the WUI fire exposure and associated toxicity and identify interventions thatsignificantly reduce chemical exposures to firefighters and inform overall public health responses.