Naproxen as an emerging pollutant in the aquatic environment: a review of toxicological effects on fish

Abstract

Naproxen (NPX) is a widely used nonsteroidal anti-inflammatory drug frequently detected in surface waters, generally at concentrations below acute thresholds, although substantially higher levels may occur in polluted wastewater discharges. Its continuous release into aquatic environments raises concerns regarding chronic exposure and its potential adverse effects on fish. This study aimed to synthesize the available evidence on NPX toxicity in fish, with particular emphasis on developmental alterations, morphological abnormalities, histopathological damage, endocrine disruption, and oxidative stress responses across different species and life stages.

The review was conducted using a structured search of international databases to identify studies on NPX occurrence and toxicity in fish. Selected publications were critically evaluated for the main biological endpoints and toxicological findings. The analysed studies revealed that early-life exposure to NPX can delay hatching and induce structural abnormalities, including pericardial and yolk sac edema, scoliosis, spina bifida, and paravertebral haemorrhage in Danio rerio and Cyprinus carpio embryos and larvae. Exposure to higher NPX concentrations was associated with thyroid dysfunction, male-biased sex ratios, reduced juvenile survival, and marked changes in estrogen receptor gene expression. Histopathological findings indicated concentration-dependent damage to the gill and kidney tissues, impairing gas exchange and osmoregulatory functions. Also, oxidative stress has been identified as a common toxicological endpoint occurring at environmentally comparable concentrations (≥1 μg/L) in juvenile Labeo rohita and adult Danio rerio. These findings support the recognition of NPX as an aquatic contaminant of concern and provide a scientific basis for its inclusion in environmental monitoring and pharmaceutical risk-assessment frameworks.