A review on in silico prediction of the environmental risks posed by pharmaceutical emerging contaminants

Computer-aided (in silico) prediction has shown good potential to support the environmental risk assessment (ERA) of pharmaceutical emerging contaminants (PECs), allowing low-cost, animal-free, high-throughput screening of multiple potential risks posed by a wide variety of pharmaceuticals in the environment based on insufficient toxicity data. This review provided recent insights regarding the application of in silico approaches in prediction for environmental risks of PECs. Based on the review of 20 included articles from 8 countries published since 2018, we found that the researchers' interest and concern in this research topic were sharply aroused since 2021. Recently, in silico approaches have been widely used for the prediction of bioaccumulation and biodegradability, lethal endpoints, developmental toxicity, mutagenicity, other eco-toxicological effects such as ototoxicity and hematological toxicity, and human health hazards of exposure to PECs. Particular attention has been given to the simultaneous discernment of multiple environmental risks and health effects of PECs based on mechanistic data of pharmaceuticals using advanced bioinformatic methods such as transcriptomic analysis and network pharmacology prediction. In silico software platforms and databases used in the included studies were diversified, and there is currently no standardized and accepted in silico model for ERA of PECs. Date suggested that in silico prediction of the environmental risks posed by PECs is still in its infancy. Considerable critical challenges need to be addressed, including consideration of environmental exposure concentration for PECs, interactions among mixtures of PECs and other contaminants coexisting in environments, and development of in silico models specific to ERA of PECs.