A Scoping Review of Magnetic Iron Oxide Toxicity Across Animal Models: Mechanistic Insights, Particle Size Effects, and Implications for Air Pollution Biomonitoring

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Abstract
Iron oxide particles (magnetite Fe3O4, hematite α-Fe2O3, and maghemite γ-Fe2O3) are prevalent constituents of atmospheric particulate matter (PM) and have gained increasing attention due to potential health implications. This scoping review provides a broad mapping of published in vivo and in vitro studies addressing the biological and toxicological effects of iron oxide particles across particle size fractions (PM10, PM2.5, PM1.0, and nanoscale) and exposure routes, including inhalation, intranasal instillation, and intravenous administration. As a scoping review, no formal risk-of-bias appraisal was conducted; however, studies were selected through predefined eligibility criteria and a structured screening workflow. Iron oxide exposure is consistently associated with oxidative stress and inflammatory responses, while mitochondrial dysfunction, genotoxicity, and neurological effects are frequently reported depending on particle characteristics and exposure context. Among studies with explicit crystalline phase identification, magnetite is most frequently associated with higher biological reactivity, whereas hematite and maghemite display more variable and context-dependent responses. Limited human evidence aligns with experimental findings, identifying magnetite-rich nanoparticles in neural and cardiovascular tissues alongside markers of oxidative and mitochondrial damage. Overall, this scoping review highlights dominant research trends, mechanistic pathways, and key knowledge gaps regarding iron oxide-containing PM, emphasizing the need for integrative approaches linking atmospheric particle characterization with toxicological research.
Funding Information
  • Secretaría de Ciencia, Humanidades, Tecnología e Innovación (CBF-2025-I-4343)

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