Toxicity Evaluation and Effect-Based Identification of Chlorine Disinfection Products of the Anti-COVID-19 Drug Chloroquine Phosphate

Abstract

Antiviral transformation products (TPs) generated during wastewater treatment are an environmental concern, as their discharge, in considerable amounts, into natural waters during a pandemic can pose possible risks to the aquatic environment. Identification of the hazardous TPs generated from antivirals during wastewater treatment is important. Herein, chloroquine phosphate (CQP), which was widely used during the coronavirus disease-19 (COVID-19) pandemic, was selected for research. We investigated the TPs generated from CQP during water chlorination. Zebrafish (Danio rerio) embryos were used to assess the developmental toxicity of CQP after water chlorination, and hazardous TPs were estimated using effect-directed analysis (EDA). Principal component analysis revealed that the developmental toxicity induced by chlorinated samples could be relevant to the formation of some halogenated TPs. Fractionation of the hazardous chlorinated sample, along with the bioassay and chemical analysis, identified halogenated TP387 as the main hazardous TP contributing to the developmental toxicity induced by chlorinated samples. TP387 could also be formed in real wastewater during chlorination in environmentally relevant conditions. This study provides a scientific basis for the further assessment of environmental risks of CQP after water chlorination and describes a method for identifying unknown hazardous TPs generated from pharmaceuticals during wastewater treatment.

Water Analysis: Emerging Contaminants and Current Issues

“…Several studies also investigated DBP formation from pharmaceuticals. For example, chloroquine phosphate, the anti-COVID-19 drug, was the focus of a pollutant DBP investigation by Hu et al, who used an EDA approach . Chlorination caused developmental toxicity in zebrafish embryos, and fractions (using preparative LC) were collected to determine the identity of the DBP(s) responsible.…”

High-Efficiency Effect-Directed Analysis Leveraging Five High Level Advancements: A Critical Review

“…124 These parameters of microalgal viability serve as an early warning of 25 Currently, Hu et al conducted a more sensitive investigation on the developmental toxicity induced by chloroquine phosphate and its transformation products by FET. 125 They expanded extensive endpoints on the phenotypes of mortality, malformation, and hatching rate. Additionally, Massei et al expanded the toxicological endpoint of zebrafish embryos to assess neurotoxicity in EDA.…”

“…Legler et al evaluated developmental abnormalities by measuring the phenotypes involving lack of swim bladder inflation and craniofacial deformities of extracts from municipal landfill soil in zebrafish . Currently, Hu et al conducted a more sensitive investigation on the developmental toxicity induced by chloroquine phosphate and its transformation products by FET . They expanded extensive endpoints on the phenotypes of mortality, malformation, and hatching rate.…”

Dual-Emission Single Sensing Element-Assembled Fluorescent Sensor Arrays for the Rapid Discrimination of Multiple Surfactants in Environments

“…Under the background of coexistence of coronavirus disease-19 (COVID-19) and human beings, surfactants are usually added into disinfectants to provide a synergistic effect with alcohols to inactivate the coronavirus. − However, the extensive use of disinfectants usually leads to the release of surfactants into the ecosystem, resulting in a series of environmental issues. In addition, exposure to surfactants with high concentrations can cause adverse health effects, such as irritation to human eyes and the skin. − In recent years, environmental health problems caused by surfactants have received extensive attention. − To date, many instrumental methods for surfactant detection have been developed, , but these techniques were hampered in wide applications due to high cost, tedious procedures, and time-consuming analysis. , Thus, it is essential to explore simple, efficient, and high-throughput methods to detect environmental surfactants for risk assessment.…”