Biosoluble AES wools are increasingly used since considered not hazardous, however, few toxicity studies are available. We evaluated cytotoxic, genotoxic-oxidative and inflammatory effects of two differently soluble AES wools, AES1 (high MgO percentage) and AES2 (high CaO percentage), on alveolar (A549) and bronchial (BEAS-2B) cells. Fiber dimensions and dissolution in cell media were evaluated by SEM analysis. Cell viability, LDH release, direct/oxidative DNA damage (fpg-comet assay) and IL-6, IL-8 and TNF-α release (ELISA), were analysed after 24 h exposure to 2-200 μg/ml. On A549 cells AES1 induced LDH release, slight direct DNA damage and oxidative DNA damage with very high IL-6 release at 100 μg/ml; AES2 induced higher DNA damage than AES1 and slight oxidative DNA damage. On BEAS-2B cells we found direct DNA damage (higher for AES1) and slight oxidative DNA damage (associated to slight increased IL-6 and IL-8 release for AES1). The higher genotoxicity of more soluble AES2 on A549 cells could be explained by higher respirable fibers % and fiber number/μg found after 24 h in RPMI-medium at 100 μg/ml. The higher membrane damage, oxidative DNA damage and inflammation induced by AES1 in A549 cells could be due to the higher D and silica percentage. These findings suggest further investigations on AES toxicity.