# Photosynthetic modulation and oxidative stress in Raphidocelis subcapitata exposed to environmentally relevant concentrations of a ketoconazole based commercial formulation

## TL;DR

This study examines how the antifungal drug ketoconazole affects a freshwater microalga, finding both stimulating and harmful effects depending on concentration and exposure time.

## Contribution

The study reveals the dual toxicity of ketoconazole on Raphidocelis subcapitata and highlights the importance of exposure duration in ecotoxicological assessments.

## Key findings

- Toxicity was observed at concentrations ≥ 1.9 µg/L, with an IC50 of 7.2 µg/L after 120 h.
- Low concentrations of ketoconazole stimulated photosynthetic activity, while higher levels induced oxidative stress.
- Exposure duration significantly influenced the physiological and biochemical responses of the microalga.

## Abstract

Antifungal drugs such as ketoconazole (KTZ) are increasingly detected in aquatic environments, raising concerns about their potential ecotoxicological effects on non-target organisms. In this study, we evaluated the physiological, biochemical, and morphological responses of the freshwater microalga Raphidocelis subcapitata exposed to environmentally relevant concentrations of KTZ. Initially, based on chronic exposure analyses, toxicity was observed at concentrations ≥ 1.9 µg/L, and the IC50 value was 7.2 µg/L after 120 h of exposure. Subsequently, assays using sub-inhibitory concentrations (2.8 and 5.6 µg L⁻¹) were conducted for 96 h and 192 h to evaluate selected endpoints, including changes in growth rate, photosynthetic pigments, cell morphology, lipid production, and oxidative stress, with exposure duration influencing these responses. These findings revealed a dual nature of KTZ toxicity: while low concentrations may stimulate photosynthetic activity, higher levels trigger oxidative stress. In addition, exposure time also influenced the effects observed in R. subcapitata. Our results underscore the importance of multivariate approaches in ecotoxicology and contribute to a deeper understanding of the environmental risks associated with pharmaceutical contaminants in freshwater ecosystems.

The online version contains supplementary material available at 10.1007/s10646-026-03066-z.