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

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 their potential health implications. This scoping review provides a broad mapping of the published in vivo and in vitro literature addressing the biological and toxicological effects of iron oxide particles across different particle-size fractions (PM₁₀, PM₂.₅, PM₁.₀, and nanoscale) and exposure routes, including inhalation, intranasal instillation, and intravenous administration. No restrictive temporal boundaries, filtering criteria, or formal quality assessment were applied, with the aim of capturing the full scope of available experimental evidence. Across the literature, particle size emerges as a central determinant of toxicity, with ultrafine and nanoscale iron oxides exhibiting enhanced surface reactivity and cellular internalization compared with larger fractions. Iron oxide exposure is consistently associated with oxidative stress and inflammatory responses, while mitochondrial dysfunction, genotoxicity, and neurological effects are also frequently reported depending on particle characteristics and exposure context. Among crystalline phases, magnetite is most often associated with higher biological reactivity, whereas hematite and maghemite display more variable and context-dependent responses. Evidence from human studies, though limited, aligns with experimental findings by 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 existing knowledge gaps regarding iron oxide–containing PM, emphasizing the need for integrative approaches linking atmospheric particle characterization with toxicological research to support air-pollution biomonitoring and environmental health assessments.