Toxicological effects of hydroxychloroquine sulfate and chloroquine diphosphate substances on the early-life stages of fish in the COVID-19 pandemic context.

Hydroxychloroquine sulfate (HCQ) and chloroquine diphosphate (CQ) have been used at increased rates to treat COVID-19 but can constitute a potential environmental risk. The objective was to evaluate the toxicity of sublethal concentrations of HCQ and CQ in zebrafish embryos/larvae. The 50% lethal concentrations (LC₅₀) of HCQ and CQ at 96 h post-fertilization (hpf) were calculated by testing various concentrations on 2,160 embryos. The LC₅₀ obtained were 560 and 800 µM for HCQ and CQ, respectively. Next, the embryotoxicity assay was performed, where 1,200 embryos were subjected to sublethal concentrations of HCQ and CQ. The hatching and heart rates were recorded. After euthanasia, photomicrographs of all larvae were taken to measure the total length, pericardial and yolk sac areas. The embryos exposed to sublethal concentrations of HCQ and CQ showed delayed hatching at 72 hpf, as well as an increase in the heart rate, larger pericardial and yolk sac areas, and body malformations at 96 hpf. The findings show that HCQ and CQ are toxic to fish in the early development phases. Understanding the mechanisms of toxicity will help extrapolate the effects of 4-aminoquinoline derivatives when they reach the aquatic environment in the context of the COVID-19 pandemic.