Hypochlorite-Driven Oxidative Dissolution Boosts Neurodevelopmental Toxicity of Cadmium Sulfide Nanoparticles in Zebrafish

Metal elements in aquatic environments are often transformed into metal sulfide nanoparticles (MSNPs), which are generally considered less toxic due to their low solubility. However, emerging evidence suggests that the oxidative dissolution of MSNPs can lead to the release of toxic metal ions. Here, we investigated the neurodevelopmental toxicity of cadmium sulfide nanoparticles (CdSNPs) in zebrafish under environmentally relevant oxidative conditions induced by hypochlorite, a common disinfectant used in wastewater treatment. We observed that the dissolution of CdSNPs in hypochlorite solutions followed an inverted U-shaped pattern with respect to hypochlorite concentration and reaction time over 24 h. Compared with CdSNP exposure alone, hypochlorite-mediated oxidative dissolution markedly potentiated neurodevelopmental toxicity, evidenced by abnormal light-dark behavioral responses in transgenic hb9:EGFP zebrafish. Mechanistic investigations revealed that the toxicity was primarily driven by dissolved cadmium ions released both in vitro and in vivo, which disrupted serotonergic, dopaminergic, and noradrenergic neurotransmitter systems. Metabolomic profiling and protein expression analyses revealed that cadmium disrupts the synthesis, metabolism, and receptor interactions of monoamine neurotransmitters. This study shows a previously underappreciated mechanism by which oxidative transformation under disinfection-relevant conditions enhances MSNP toxicity, offering critical insights into the ecological and health risks associated with metal sulfide nanoparticles in aquatic systems.