title: Quantitative Adverse Outcome Pathway Analysis of Hatching in Zebrafish with CuO Nanoparticles.
abstract: 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. Cu(2+) 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.
authors.affiliation: Marine Science Institute, University of California, Santa Barbara , Santa Barbara, California 93106, United States.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Muller
authors.affiliation: Center for Environmental Implications of Nanotechnology, University of California, Los Angeles , Los Angeles, California 90095, United States.
authors.forename: Sijie
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Ecology, Evolution and Marine Biology, University of California, Santa Barbara , Santa Barbara, California 93106, United States.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nisbet
mesh_terms: D000818:Animals; D003300:Copper / Q000493:pharmacokinetics / Q000633:toxicity*; D054750:Ecotoxicology / Q000379:methods; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000633:toxicity; D004798:Enzymes / Q000378:metabolism; D005260:Female; D007700:Kinetics; D053768:Metal Nanoparticles / Q000633:toxicity*; D008962:Models, Theoretical; D015027:Zebrafish / Q000196:embryology*
chemical_list: D004791:Enzyme Inhibitors; D004798:Enzymes; D003300:Copper; C030973:cupric oxide