Environmental impact assessment of COVID-19 therapeutic solutions. A prospective analysis

Several medicinal products for human use are currently under consideration as potential treatment for COVID-19 pandemic. As proposals cover also prophylactic use, the treatment could be massive, resulting in unprecedent levels of antiviral emissions to the aquatic environment. We have adapted previous models and used available information for predicting the environmental impact of representative medicinal products, covering the main groups under consideration: multitarget antiparasitic (chloroquines and ivermectin), glucocorticoids, macrolide antibiotics and antiviral drugs including their pharmacokinetic boosters. The retrieved information has been sufficient for conducting a conventional environmental risk assessment for the group of miscellaneous medicines; results suggest low concern for the chloroquines and dexamethasone while very high impact for ivermectin and azithromycin, even at use levels well below the default value of 1% of the population. The information on the ecotoxicity of the antiviral medicines is very scarce, thus we have explored an innovative pharmacodynamic-based approach, combining read-across, quantitative structure-activity relationship (QSAR), US EPA's Toxicity Forecaster (ToxCast) in vitro data, pharmacological modes of action, and the observed adverse effects. The results highlight fish sublethal effects as the most sensitive target and identify possible concerns. These results offer guidance for minimizing the environmental risk of treatment medication for COVID-19.