# Chronic Exposure to Niclosamide Disrupts Structure and Metabolism of Digestive Glands and Foot in Cipangopaludina cathayensis

## TL;DR

Long-term exposure to niclosamide harms the digestive and foot tissues of a freshwater snail, potentially disrupting its survival and ecosystem role.

## Contribution

This study reveals chronic niclosamide exposure disrupts inter-organ metabolic coupling in non-target snails, a novel toxicological mechanism.

## Key findings

- Niclosamide accumulates more in snail digestive glands than foot tissues, causing structural and metabolic damage.
- Digestive gland metabolism impairment correlates with foot tissue atrophy and locomotor dysfunction.
- Chronic exposure may destabilize mollusk populations and pose ecosystem risks.

## Abstract

Niclosamide is widely used to control snails that transmit schistosomiasis. However, it can also harm non-target freshwater snails with important ecological functions. In this study, the mud snail Cipangopaludina cathayensis was exposed to environmentally relevant concentrations of niclosamide for 60 days to evaluate its chronic toxic effects. Niclosamide accumulated more in the digestive glands than in the foot, causing tubular atrophy, inflammatory responses, and depletion of essential nutrients. Structural damage was also observed in the foot tissue, including vacuolization and muscle fiber atrophy. Alteration in the nutrient metabolism in the digestive glands may adversely influence foot function, indicating a metabolic linkage between these organs. Such impairments could compromise snail survival, feeding, and movement, thereby posing potential ecosystem risks. These findings underscore the need for more environmentally responsible use of niclosamide.

Niclosamide has been the primary molluscicide for schistosomiasis control for over 50 years, but its chronic effects on inter-organ interactions in non-target mollusks remain poorly understood. Cipangopaludina cathayensis, a dominant species in East Asian schistosomiasis-endemic regions, was chronically exposed to environmentally relevant concentrations of niclosamide to assess its toxic effects. Digestive glands accumulated more niclosamide than the foot tissues. Prolonged exposure was associated with metabolic impairment of the digestive glands, characterized by tubular atrophy, inflammatory reactions, and depletion of nutrient components. Foot tissues exhibited epithelial lesions and muscle fiber atrophy. Alterations in foot structure were associated with changes in digestive gland nutrient status. Niclosamide exposure may weaken the metabolic coupling between these organs, thereby impairing locomotor function. At the population level, persistent niclosamide exposure may destabilize mollusk trophic-level populations, ultimately leading to ecological consequences. Our findings demonstrate the toxicological risks of niclosamide to freshwater mollusks.