Celestial hazards: immunological and pulmonary effects of lunar and Martian regolith simulants

Lunar and Martian dusts present emerging health hazards to astronauts, particularly during long-duration missions such as those planned under NASA's Artemis program. These extraterrestrial regoliths possess unique physicochemical properties-such as angular morphology, high surface area, and reactive mineral phases-that distinguish them from terrestrial dust and may influence their biological activity. This review synthesizes current findings from in vitro and in vivo toxicological studies involving lunar and Martian dust and their simulants. Lunar dust, which contains elevated levels of silica and nanophase metallic iron, has been associated with pulmonary inflammation, neutrophilic infiltration, and indications of fibrotic remodeling in animal models. Cell-based assays have also reported apoptosis, necrosis, and pro-inflammatory cytokine production in macrophages, epithelial cells, and fibroblasts following exposure. Martian dust simulants have shown cytotoxic effects and preliminary signs of neurotoxicity in vitro, although these findings are limited and based on analogs that may not fully represent actual Martian material. These findings show certain challenges of extrapolating human risk from simulants that may not fully replicate the properties of actual regolith. Future research must prioritize physiologically relevant inhalation models, and chronic low-dose exposure scenarios. These studies should also account for the combined impact of spaceflight-associated stressors-such as radiation, microgravity, and altered breathing mechanics-on toxicity outcomes. Mechanistic studies incorporating transcriptomic and proteomic tools, alongside standardized methodologies, will be essential for establishing evidence-based safety thresholds for human space exploration.