Avaliação toxicológica dos antirretrovirais entricitabina e fumarato de tenofovir desoproxila em Microcystis novacekii e Chlorella vulgaris.

Abstract

Aquatic contamination by pharmaceutical residues, including antiretrovirals (ARV), has been reported in various water bodies worldwide. Among the ARV detected, emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), both used in the HIV pre-exposure prophylaxis (PrEP) regimen, have been found in surface and wastewater, posing potential ecotoxicological risks. Therefore, the objective of this study was to assess the potential toxic effects of these ARV, both individually and in combination, on the cyanobacterium Microcystis novacekii and the microalga Chlorella vulgaris, and to estimate their environmental risk. Ecotoxicological assays were conducted by exposing the organisms to different concentrations of the ARV, both individually and combined, over a 96-hour period. Median Effective Concentrations (EC50) were determined, and effects on cellular growth were evaluated. Results showed that, individually, TDF exhibited no toxicity to either organism, while FTC was classified as slightly toxic to M. novacekii. The combination of both drugs significantly increased toxicity in both species, suggesting a possible synergistic effect. For the pharmaceutical formulation containing FTC and TDF, a different response pattern was observed, with increased growth inhibition of the cyanobacterium and stimulation of microalgal growth, indicating a possible influence of excipients in the formulation on the test organisms. In the Environmental Risk Assessment (ERA), the ARV FTC presented a moderate risk to both test organisms in untreated effluents, representing a potential environmental threat. It is concluded that, although individual ARV exhibited low toxicity, their combination and the presence of excipients may enhance or alter toxicological effects and indicate a significant environmental risk. These findings underscore the need to evaluate drug combinations in ecotoxicological studies and highlight the importance of implementing regulations concerning the presence of pharmaceutical residues in water, as well as developing effective wastewater treatment methods to mitigate the impact of these emerging contaminants.