Adverse effects and underlying mechanism of rare earth elements

BACKGROUND: Rare earth elements (REEs) have found broad application in a range of industries, including electronics, automotive, agriculture, and healthcare. However, their widespread utilization and release into the environment pose potential risks of human exposure. Despite extensive research on REEs toxicity, the relationship between exposure and subsequent health concerns remains ambiguous. Given that the biological effects of REEs can vary based on their design and application, assessing their toxicity can be highly challenging. OBJECTIVE: This review is to offer a thorough comprehension of REEs' application and toxicity, guiding future research and policy-making to safeguard public health and environmental integrity. METHODS: A systematic search across PubMed, Web of Science, Cochrane Library, and Embase was conducted using the terms: ("rare earth" OR "lanthanoid") AND ("health hazard" OR "toxic" OR "adverse health effect"). From 5,924 initial records, 89 studies were selected through deduplication and two-stage screening to assess systemic toxicity of REEs. An additional 100 articles on REEs mechanisms and applications were incorporated via citation tracking. All selections followed PRISMA guidelines with dual-author verification to ensure rigor. CONCLUSION: The review emphasizes REEs' applications in various domains and documents potential environmental pathways. Furthermore, it elaborates on current processes to assess REEs-related toxicity across different model organisms and cell lines, estimating health threats posed by REEs exposure. Finally, based on the findings of both in vivo and in vitro experiments, the potential toxic mechanisms of REEs are detailed. To guide future research and policy development to safeguard public health and environmental integrity.