Health Risk Assessment for Rare Earth Ions: From End Point Identification of Cytotoxicity to Mixed Toxicity...

Area of Science:

• Environmental Science
• Toxicology
• Computational Biology

Background:

• Rare earth elements (REEs) are increasing environmental contaminants.
• Assessing REE health risks is difficult due to varied cytotoxicity data and complex exposures.

Purpose of the Study:

• To develop a comprehensive framework for assessing the cytotoxic risks of 16 rare earth ions (REIs).
• To establish a standardized, scalable, and integrative risk assessment toolkit for REEs and other emerging multielement contaminants.

Main Methods:

• Integrated high-throughput screening of single and binary REI exposures across eight human cell lines.
• Utilized machine learning models for predicting mixture cytotoxicity.
• Applied models to population exposure scenarios and validated with human primary hepatocytes.

Main Results:

• Identified ATP depletion as a robust benchmark point of departure (BPOD) for REE cytotoxicity.
• Revealed predominantly antagonistic interactions among REEs in binary exposures.
• Machine learning models showed strong predictive performance for mixture cytotoxicity.

Conclusions:

• The developed framework provides a reliable method for assessing REE health risks.
• High health risks were predicted for populations in mining areas, while general population risks were negligible.
• The study offers a standardized toolkit for evaluating emerging multielement contaminants.