Human Neural Organoids and Nerve-on-Chip Models for Environmental Neurotoxicity: Integrating Central and Peripheral Nervous System Platforms with Precision Neuropharmacology

Environmental neurotoxicity affects the central nervous system (CNS), peripheral nervous system (PNS) and the interfaces that regulate toxicant access. This review evaluates human neural organoids and nerve-on-chip systems for investigating exposure responses and neuroprotective interventions. Direct environmental-toxicant evidence is stronger in CNS models, where studies identify developmental, cellular and activity changes. Most three-dimensional PNS studies establish capabilities through genetic disease, metabolic injury or chemotherapy exposure; environmental hazard assessment requires validation in the intended platform. Comparisons across toxicant classes depend on neural identity, developmental stage, exposure duration and delivered dose. Recurring stress responses suggest convergent injury processes, while causal mechanisms and functional rescue require targeted evidence. We distinguish starting-cell quality, differentiation variability and final-model attributes, and organize evaluation around model identity, functional competence, assay performance and qualification for a defined context of use. Broader use in hazard screening and regulatory decision support requires measured exposure, appropriate biological replication, application-specific reference compounds and independent interlaboratory testing.