ZnO Nanoparticle Exposure Disrupted Iron-Sulfur Protein Functions to Increase Macrophage Erythrophagocytosis and Disturb Systemic Iron Recycling.

Summary

In mice, ZnO nanoparticle exposure caused anemia by disrupting splenic iron metabolism. This involved macrophage metabolic reprogramming that increased erythrophagocytosis and an impaired ferroportin response, leading to iron retention and defective iron recycling. These mechanistic insights directly inform risk assessment of ZnO used in sunscreens and other cosmetics.

Key Findings

• ZnO nanoparticle exposure in mice produced overt anemia linked to disrupted splenic iron metabolism.
• Macrophage metabolic reprogramming increased erythrophagocytosis while ferroportin response was blunted, causing iron retention.
• Findings implicate iron–sulfur protein dysfunction and defective macrophage iron recycling as central mechanisms.

Clinical Implications

Cosmetic safety assessments should incorporate endpoints for reticuloendothelial iron handling (e.g., ferroportin signaling, erythrophagocytosis) and consider systemic exposure from chronic dermal use. Regulatory testing may need to evaluate hematologic effects in long-term exposure models.

Limitations

• Preclinical mouse data; human exposure–response relationships remain untested
• Exposure levels, routes, and chronicity relative to consumer sunscreen use are not fully defined

Future Directions

Quantify dermal absorption and systemic distribution of cosmetic-grade ZnO NPs in humans and assess hematologic endpoints in chronic exposure studies; evaluate formulation factors that mitigate macrophage iron disruption.