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The development of novel renewable fuels is paramount for reducing carbon emissions and mitigating climate change. Biofuels, such as biodiesel and lignin-based fuels could play an important role for this endeavour, particularly in Sweden. However, particles generated from combustion of such fuels could have a negative impact on human health, similar to traditionally used fuel. Knowledge on these aspects is scarce. The aim of this project is to evaluate lung toxicity of particles generated from combustion of novel biofuels such as ‘new generation’ biodiesel and lignin-based fuels that are originating from raw forest material. To this end the project will use advanced 3D in vitro models of the human lungs and experimental setups that resemble human exposure, i.e. acute and chronic exposure (3 months) at low, realistic doses. Traditional toxicological endpoints (e.g. inflammation, DNA damage) will be combined with RNA-sequencing in order to gain deep insight into potential mechanisms of toxicity and generate new hypotheses. We will also use 3D models representative of vulnerable populations such as individuals with asthma. The 3D models will be co-cultured with immune cells to evaluate the influence of the immune component for toxicity. Diesel exhaust particles will be used as reference particles for benchmarking. Overall, this project will provide relevant information on the toxicity of novel fuels that is of critical value for risk assessment and sustainable development.