The biologically effective dose in inhalation nanotoxicology

Area of Science:

• Nanotoxicology
• Environmental Health Sciences
• Materials Science

Background:

• The biologically effective dose (BED) is crucial for understanding how toxins cause harm.
• In nanoparticle (NP) toxicology, the BED is the specific entity within a dose that drives toxic effects, influencing structure-activity relationships and regulatory assessments.
• Traditional dose metrics like mass are insufficient for NPs, as surface area, shape, and dissolution properties also play significant roles.

Purpose of the Study:

• To review current knowledge on the biologically effective dose (BED) for various types of nanoparticles (NPs).
• To highlight the importance of BED in predicting and understanding NP toxicity.
• To discuss challenges and future directions in nanotoxicology related to BED.

Main Methods:

• Review of existing literature on nanoparticle (NP) biologically effective dose (BED).
• Analysis of NP properties such as solubility, ion release, surface charge (zeta potential), oxidative potential, and physical dimensions (aspect ratio).
• Discussion of toxicological outcomes including oxidative stress, inflammation, genotoxicity, and frustrated phagocytosis.

Main Results:

• For soluble NPs (e.g., copper, zinc), released ions can indicate BED, with rapid dissolution in acidic environments leading to inflammation.
• For insoluble NPs, zeta potential is a potential BED metric, reflecting interactions with biological compartments like the phagolysosome.
• Oxidative potential is a widely studied BED indicator, correlating with NP-induced cell toxicity, inflammation, and DNA damage.
• High aspect ratio NPs (fibers, nanoplatelets) pose unique risks due to deposition patterns and incomplete phagocytosis, leading to inflammation.

Conclusions:

• Understanding the biologically effective dose (BED) is critical for assessing nanoparticle (NP) toxicity.
• Different NP types require distinct BED metrics, including ion release, zeta potential, oxidative potential, and consideration of physical characteristics.
• Further research is needed to fully elucidate and utilize BED for comprehensive NP risk assessment and safe design.