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The comparatively strong effect of kaolin on NR8383 cells found here differs from earlier findings, which demonstrated a cytotoxicity of 100 µg/mL kaolin on NR8383 cells after 5 days only [29]. Again, the low cytotoxicity of kaolin in that study may be explained by the presence of 10% serum, known to mitigate the in vitro response of silica [30,31]. However, the attenuated cytotoxicity described by Gao and co-workers [29] is in line with the moderate in vivo response seen here in the rat lung for kaolin, suggesting that the milieu of the inner lung surface mainly composed of lung surfactant and lung lining fluid mitigates kaolin effects. Especially, dipalmitoylphosphatidylcholine (DPPC), the major phospholipid of the lung surfactant, inhibited cytotoxic effects of quartz and kaolin [29]. The lower toxicity of kaolin compared to quartz, as found here in vivo, has also been documented in cell studies [26]. However, bentonite particles bind to proteins and surfactant components as well [32], but for bentonite, a protein and/or lipid corona formation was not sufficient to inhibit inflammatory effects. Interestingly, the CD68 staining intensity of many alveolar macrophages was low in bentonite-laden lungs (c.f. Figure 6h), suggesting beginning cell damage upon bentonite inclusion. Meanwhile, there is compelling evidence that the toxicity of silica material, including quartz and amorphous silica as well, is linked up with the steric organization of superficially located silanol groups responsible for membranolytic activity, cell surface receptor interaction, and proteasome activation [31]. As kaolin and bentonite share tetrahedric SiO₂ layers at their outer surface [33], a silica-like bioactivity may be expected for both aluminosilicates, whereby bentonite with its larger BET surface (51.9 vs. 24 m²/g) should be about twice as reactive. Furthermore, a bolus administration of particles with a large surface may adsorb high amounts of lung surfactant compromising normal lung function [34]. Such a disturbance of the inner lung milieu may especially apply for bentonite, which adsorbs proteins faster and more effectively than kaolin (Haase, personal communication). Adsorption of proteins by bentonite may also explain the biphasic responses observed here for the activities of LDH and GLU in cell culture supernatant. It may be speculated that these enzymes are bound and inactivated by bentonite and that this effect is especially evident under serum-free conditions.