Firefighting is recognized as one of the most dangerous occupations due to the frequent exposure to high concentrations of hazardous materials encountered at fire scenes. They are exposed to carbon monoxide, benzene, and particulate matter which contain high levels of toxic compounds, mostly generated by combustion of various materials. Several studies have linked these exposures to respiratory decline, airway inflammation, and neurological disorders. However, there are still few studies that associate the chemical composition of these aerosols with specific toxicological impacts on health. In the present work, the toxic effects of organic extracts from filters previously placed on firefighters¿ work clothing were analyzed using brain cell models. Three filter samples from firefighters working in different environments were employed in this study. On the one hand, the organic extracts of these filters were analysed using GC-MS as previously described in Villasclaras et al (2022) to characterize the chemical composition regarding biomass burning (BB) indicators and polycyclic aromatic hydrocarbons (PAHs) compounds. To investigate the toxic effect of these extracts, we employed the neuroblastoma cell line SH-SY5Y and brain organoids, obtained by 40-day differentiation from the human BJ-SeV-iPSC cells according to Pedrosa et al (2023). Cell viability and the release of reactive oxygen species (ROS) were evaluated after 72h of exposure at 30 dm3 eq. air/ml. To simulate the effects of acute and chronic exposure to brain cells, brain organoids were exposed to filter extracts for 72 hours at 30 dm3 eq. air/ml, and for 30 days at 8 dm3 eq. air/ml, respectively. Lipidomic analyses was carried out on lipid extracts from both acute and chronic exposed organoids. Chemical analysis of sample 1 (firefighter in fire periphery) had low levels of PAHs and BB indicators: sample 2 (firefighter with ignition torch) had higher values of PAHs, notably of benzofluoranthrenes (150 ng/m3) and benzo[a]pyrene (110 ng/m3). Sample 3 (firefighter fire control) had besides PAHs higher values of BB indicators, mostly of levoglucosan (93 ug/m3), and very high levels of retene (370 ng/m3), a PAH related to conifers burning. Concerning the neuroblastoma cell line, cell viability was not affected after 72h, and ROS only increased in samples 2 and 3 (150% and 300% versus vehicle, respectively, see Figure 1). In brain organoids, cell viability was not perturbed, and higher ROS values were also detected for sample 3 (200% respect the vehicle). The lipidomics results showed very different lipid profiles for each of the treatments, both for acute and chronic exposure. Important changes in signalling lipids, like ceramides, sphingosines and phosphatidylinositols have been observed. Altogether, the findings of this research indicate that the particulate matter accumulated in the small filters carried by the firefighters in their workwear can exert biological effects on neuroblastoma and brain cells. It is worth noting that very low doses under a chronic exposure of 30 days caused important lipid changes, suggesting that the occupational exposure of firefighters can pose a risk to their brain health.