Valence-Dependent Transformation of Copper-Based Pesticides: Divergent Sulfidation Pathways and Differential Toxicity of Cu, Cu2O, and Cu(OH)2 in Zebrafish.

Copper-based particulates, from nanomaterials to commercial pesticides, are widely used in agriculture. Runoff from high-dose applications leads to accumulation in aquatic systems, where they interact with sulfide-rich environments. Although sulfidation is considered as a detoxification pathway for metal-based nanomaterials, its effects on the developmental toxicity of copper-based pesticides with different oxidation states remains unclear. Herein, we investigated the sulfidation of copper nanoparticles (Cu NPs), Cu2O, and Cu(OH)2 pesticides to link physicochemical transformations with zebrafish developmental toxicity. Transformation pathways were valence-dependent, i.e., Cu NPs formed Cu2S via a core-shell mechanism, whereas Cu2O and Cu(OH)2 transformed via dissolution-precipitation. After sulfidation, Cu NPs and Cu2O exhibited reduced copper ion release and alleviated hatching inhibition. In contrast, sulfidation of Cu(OH)2 aggravated hatching inhibition. Sulfidation also led to organic additives removal, improving survival despite persistent hatching inhibition in the Cu(OH)2 group. Histological and cellular analyses confirmed cardiac injury and apoptosis after exposure to copper-based particles and their sulfidation products. Transcriptional profiling showed that sulfidation partially normalized cardiac development genes in Cu NPs and Cu2O groups but not in the Cu(OH)2 group. These findings demonstrate that sulfidation does not universally mitigate copper toxicity, highlighting the importance of copper oxidation states in environmental risk assessment.