Acute and neurological toxicities of endosulfan I, endosulfan sulfate, endosulfan diol, and endosulfan ether in zebrafish (Danio rerio) embryos: Developmental effects on heart and brain formation

Environ Res. 2025 Jun 24:284:122235. doi: 10.1016/j.envres.2025.122235. Online ahead of print.

Abstract

Endosulfan (ES) is classified as a persistent organic pollutant (POP), and its use has been banned in the agricultural sectors of most countries. It is metabolized into several compounds, among which ES sulfate is frequently detected in the environment. In this study, the acute toxicities of α-ES, ES sulfate, ES diol, and ES ether were evaluated in zebrafish (Danio rerio) embryos. No acute toxicity was observed at tested concentrations ranging from 0.125 to 1.0 mg/L. However, severe morphological deformities were detected in embryos treated with α-ES and ES sulfate. Whole body length was significantly reduced in two chemicals-treated embryos. Electroencephalogram analysis revealed a marked increase in ictal-like events in embryos exposed to α-ES and ES sulfate. α-ES caused abnormal development of the midbrain and hindbrain at 72 h post-fertilization (hpf), while ES sulfate induced hindbrain malformation at the same stage. Abnormal atrial formation, along with cardiac dysfunction, was observed in embryos treated with α-ES and ES sulfate. These cardiac abnormalities were associated with the downregulation of amhc and gata4, genes involved in atrial and cardiac development. A significant increase in apoptotic cells was observed in the pericardial regions of embryos exposed to α-ES and ES sulfate. Collectively, these findings suggest that the transformation of ES into ES sulfate warrants concern due to its retention of ES toxicity and environmental persistence.

Keywords: Apoptotic cells; Brain and cardiac abnormalities; Endosulfan; Endosulfan sulfate; Ictal-like events; Zebrafish embryos.