Silver nanoparticle (AgNP), neurotoxicity, and putative adverse outcome pathway (AOP): A review.

Summary

This review proposes the first integrated Aggregate Exposure Pathway/Adverse Outcome Pathway framework specific to AgNP-induced neurotoxicity. It synthesizes factors influencing toxicity (size, coating, shape, route), maps molecular initiating events to neurotoxic outcomes, and illustrates benchmark dose use to compare heterogeneous studies.

Key Findings

• Introduces the first AEP/AOP specifically linking AgNP exposure sources and routes to molecular initiating events and neurotoxic outcomes.
• Identifies key determinants of neurotoxicity, including particle size, coating, shape, and exposure route, with evidence of brain accumulation across studies.
• Demonstrates how benchmark doses can enable cross-study comparison of in vitro dose-response and in vivo exposure-response data.

Clinical Implications

Manufacturers and clinicians should consider minimizing AgNP exposure in leave-on products, optimize particle design (size/coating) to mitigate neurotoxicity risk, and support monitoring frameworks aligned with the proposed AOP.

Limitations

• Heterogeneity in AgNP types and exposure routes limits direct comparability.
• Not a PRISMA-based systematic review; potential selection bias in included studies.

Future Directions

Standardize particle characterization and exposure metrics, validate key event relationships in the AOP with longitudinal neurobehavioral studies, and derive health-protective exposure limits for consumer products.