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Cellular exposure to diluted exhaust gas is a promising method to assess the adverse effects of road traffic on human health. To fully understand the potential correlation between emission patterns, vehicle technologies and cellular toxicity in real-world scenarios, further research is needed. This study evaluates the toxicity of exhaust emissions from two advanced technology vehicles in real-world driving conditions. One vehicle is a gasoline direct injection (GDI) with a particle filter (GPF), while the other is a gasoline port fuel injection (PFI) hybrid without a GPF. The vehicles were tested on a chassis dyno using a Real Driving Emissions (RDE) test cycle that replicates on-road conditions. The test cycle included both cold and hot starting engine conditions. Human epithelial A549 cells were exposed to diluted exhaust using an Air Liquid Interface (ALI) system to assess toxicity. Τhe particle dose during cell exposure simulated human inhalation in an urban environment.