Quantitative Adverse Outcome Pathway Analysis of Hatching in Zebrafish with CuO Nanoparticles

• Published in: Environmental science & technology 2015-10, Vol.49 (19), p.11817-11824
• Main Authors: Muller, Erik B, Lin, Sijie, Nisbet, Roger M
• Format: Article
• Language: English
• Subjects: Animals; Bioaccumulation; Copper; Copper - pharmacokinetics; Copper - toxicity; Danio rerio; Dissolution; Ecotoxicology - methods; Embryo, Nonmammalian - drug effects; Embryo, Nonmammalian - metabolism; Enzyme Inhibitors - toxicity; Enzymes; Enzymes - metabolism; Female; Freshwater; Kinetics; Metal Nanoparticles - toxicity; Models, Theoretical; Nanoparticles; Toxicity; Zebrafish; Zebrafish - embryology
• ISSN: 0013-936X; 1520-5851
• DOI: 10.1021/acs.est.5b01837

This study develops and evaluates a mechanistic model of the hatching of zebrafish eggs that were exposed to CuO engineered nanoparticles (ENP) in a high-throughput screening system and places this model in an adverse outcome pathway (AOP) that also includes CuO ENP dissolution and Cu bioaccumulation. Cu2+ inhibits the proteolytic activity of Zebrafish Hatching Enzyme 1 and thereby delay or impair hatching success. This study demonstrates that noncompetitive inhibition kinetics describe the impact of dissolved Cu on hatching; it is estimated that indefinitely long exposure to 1.88 μM dissolved Cu in the environment reduces hatching enzyme activity by 50%. The complexity arising from CuO ENP dissolution and CuO ENP assisted bioaccumulation of Cu has led to apparently contradictory findings about ion versus “nano” effects on hatching. Model-mediated data analyses indicate that, relative to copper salts, CuO ENPs increase the uptake rates of Cu into the perivitelline space up to 8 times. The toxicity assessment framework in this study can be adapted to accommodate other types of toxicant, environmental samples and other aquatic oviparous species.