COMBINED EFFECTS OF PHARMACEUTICAL COMPOUNDS AND MICROPLASTICS ON FISH HEALTH: A REVIEW OF EXPOSURE, TOXICITY, AND ECOLOGICAL RISKS
Pharmaceutical compounds and microplastics are ubiquitous aquatic pollutants that frequently co-exist in aquatic environments; however, their combined effects on fish cannot be accurately predicted from studies investigating each pollutant individually. Pharmaceutical compounds can disrupt conserved molecular targets even at low concentrations, whereas microplastics are particulate materials that also act as surfaces capable of sorbing, transporting, and releasing chemical contaminants. This review synthesizes current knowledge on the co-exposure of fish to pharmaceuticals and microplastics, with a particular focus on toxicokinetics, organ toxicity, and associated ecological risks. Findings from direct co-exposure studies indicate that interactions range from synergistic and additive to antagonistic, depending on factors such as particle size, polymer composition, plastic aging, biofilm formation, water chemistry, exposure sequence, pharmaceutical properties, and tissue-specific uptake. The intestine and the gut–liver axis have emerged as particularly vulnerable targets, while the plastisphere may harbor increased abundances of antibiotic resistance genes and exert stronger selective pressure under antibiotic co-exposure. However, most available studies have employed pristine spherical polystyrene microplastics, short exposure durations, and concentrations exceeding environmentally relevant levels. Furthermore, only a limited number of studies have incorporated mixture toxicity models or investigated sub-organismal mechanisms to predict population-level effects. Current evidence suggests that, under environmentally realistic conditions, microplastics should not generally be regarded as vectors of pharmaceutical contaminants but rather as carriers, sinks, sources, and independent stressors. Future risk assessments should prioritize environmentally aged microplastics, realistic pharmaceutical mixtures, time-dependent internal exposure, species-specific sensitivity, and adverse outcome pathways to improve ecological risk predictions.