Standard Reference Material^® (SRM^®) 2585 can be considered as a model sample of settled indoor dust. At least 168 adsorbed chemicals were identified and quantified, generating a complex and potentially toxic mixture. Inhalable fractions PM₁₀ and PM_2.5 were isolated and compared to SRM^® 2585 for their intrinsic properties and their respiratory toxicity using pertinent normal human bronchoepithelial (NHBE) cells. The intrinsic oxidative potential (OP) of SRM^® 2585 and its subfractions was measured in acellular conditions, together with ROS generation and endotoxin content. For SRM^® 2585 and PM₁₀, cellular responses were evaluated on NHBE cells after 72 h exposure (1.1 to 110 µg/mL). The presence of endotoxins associated with an intrinsic prooxidant potential did not lead to the induction of an inflammatory response. Interestingly, cytokine production was decreased, strongly for IL-1β and to a lesser extent for IL-6. Only PM₁₀ induced an acute toxicity. In parallel, mutagenicity was evaluated from organic extracts. Mutagenic profiles indicated the concomitant presence of nitro-PAHs in addition to the previously reported PAHs. This could be of concern for long-term health effects in a context of chronic exposure.