Toxicity mechanisms and bioavailability of copper to fish based on an adverse outcome pathway analysis

Abstract

Copper (Cu) exists in a variety of forms in different aquatic environments, and affects their bioavailability. In this study we provide a systematic review on toxicity of Cu which focuses on identifying evidence in the mechanisms of Cu toxicity, and apply an adverse outcome pathway (AOP) analysis to identify multiple potential mechanisms and their interactions of Cu toxicity to fish. This analysis process included the mechanisms of behavior toxicant, oxidative toxicant, ion regulation disruption toxicity, as well as endocrine disruption toxicity. It was found that at low levels of Cu exposure, swimming, avoid predators, locating prey and other sensory functions will be impaired, and the organism will suffer from metabolic alkalosis and respiratory acidosis following the inhibition of the carbonic anhydrase active. The main pathway of acute toxicity of Cu to fish is the inhibition of the Na⁺/K⁺-ATPase enzyme, and lead to reduced intracellular sodium absorption, as well as Cu-induced increased cell permeability, in turn resulting in increased sodium ion loss, leading to cardiovascular collapse and respiratory insufficiency. The endocrine disruption toxicity of Cu to fish caused growth inhibition and reproductive reduction. In addition, there are several key pathways of Cu toxicity that are affected by hardness (e.g., Ca²⁺) and intracellular DOC concentrations, including inhibiting Cu-induction, improving branchial gas exchange, altering membrane transport functions, decreasing Na⁺ loss, and increasing Na⁺ uptake. The results of the AOP analysis will provide a robust framework for future directed research on the mechanisms of Cu toxicity.