# Bioaccumulation and toxicity of imatinib, cyclophosphamide and its transformation product carboxyphosphamide in the freshwater mussel Elliptio complanata

## TL;DR

This study examines how two cancer drugs, cyclophosphamide and imatinib, affect freshwater mussels, finding that imatinib is more bioavailable and potentially more toxic.

## Contribution

The study provides new insights into the bioaccumulation and toxicity of antineoplastic drugs in freshwater mussels, highlighting imatinib's potential environmental risks.

## Key findings

- Cyclophosphamide showed low bioaccumulation but was linked to oxidative stress and changes in gonad indices.
- Imatinib had higher bioavailability and was associated with DNA damage and reduced neural activity in mussels.
- Chronic exposure to these drugs from wastewater could pose environmental risks despite low short-term concentrations.

## Abstract

Pharmaceutical compounds primarily enter the environment through wastewater treatment plants, where they are not completely removed. Antineoplastic drugs, such as cyclophosphamide and imatinib, are particularly concerning due to their cytotoxic effects at low concentrations. The purpose of this study was to determine the bioavailability and toxicity of these 2 drugs to freshwater mussels, known to thrive in urban areas. Freshwater mussels Elliptio complanata were exposed to increasing concentrations (4, 20, and 100 µgL− 1) of cyclophosphamide and imatinib for 96 h at 15 °C. Although a low bioaccumulation factor of 0.27 was measured for cyclophosphamide, its level in tissues was correlated with lipid peroxidation in gonads and gonadosomatic index (GSI), which could suggest that it is involved in oxidative stress and increased GSI. The metabolite carboxyphosphamide was never detected in mussel tissue. Imatinib was more bioavailable with a measured bioaccumulation factor of 2.3. Tissue levels of imatinib were correlated with DNA damage (DNAd) in both the digestive gland and gonads while decreased acetylcholine esterase activity was observed, suggesting that it is involved in decreased neural activity and DNAd in mussels. Based on these findings, imatinib could disrupt the repair of oxidized DNAd, leading to the accumulation of alkali-labile sites in DNA. While the short-term exposures resulted in low cytostatic concentrations in mussel tissues, chronic exposure from continuous wastewater releases with the rising use of cytostatic drugs for cancer treatments could still pose a potential environmental risk that warrants further investigation.

The online version contains supplementary material available at 10.1007/s10646-025-02976-8.