Toxicity of the Antiretrovirals Lamivudine, Dolutegravir, and Tenofovir on the Microalga Chlorella vulgaris
Abstract
This study evaluated the toxicity of the three antiretrovirals: dolutegravir (DTG), tenofovir (TDF), and lamivudine (3TC), both as commercial medicines and active pharmaceutical ingredients (APIs), on the microalga Chlorella vulgaris. Acute (4-d) and chronic (14-d) toxicity tests were conducted following OECD Guideline 201 (2011). Among the evaluated substances, DTG-API showed the highest toxicity, while 3TC was the least toxic. Results indicate that excipients modulate toxicity and that chronic exposures may induce tolerance mechanisms in C. vulgaris. DTG-API was classified as “toxic,” with EC50 values of 3.3 mg/L (acute) and 5.9 mg/L (chronic). DTG-Med also showed acute toxicity (EC50 = 7.1 mg/L) but was almost nontoxic chronically. TDF-Med was considered “slightly toxic” acutely (EC50 = 92.9 mg/L) and “practically non-toxic” in chronic exposure. TDF-API showed higher chronic toxicity (EC50 = 88.7 mg/L) compared to its commercial form. 3TC-Med and 3TC-API were “practically non-toxic” under both conditions. Hormesis effects were observed at low concentrations of TDF-Med. Overall, APIs were more toxic than commercial medicines, suggesting a role of excipients in reducing toxicity. In addition, the Environmental Risk Assessment identified 3TC as the compound with the highest risk quotients, particularly in surface waters and wastewater treatment plant effluents, where medium to high ecological risks were observed (RQ > 7.0). In contrast, TDF presented insignificant risk…
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