Physicochemical determinants of zinc oxide nanoparticle developmental toxicity in zebrafish (Danio rerio): A systematic review and structured quantitative synthesis.

Abstract

Zinc oxide nanoparticles (ZnO NPs) are widely used, but their developmental toxicity varies substantially across experimental systems because nanoparticle properties and exposure conditions alter their biological identity. This systematic review and structured quantitative synthesis synthesized evidence on ZnO NP developmental toxicity in zebrafish (Danio rerio) embryos and larvae, with emphasis on physicochemical determinants and mechanistic interpretation. PubMed/MEDLINE, Scopus, and Web of Science were searched through 28 August 2026. Thirty-six studies met the eligibility criteria, and study-level risk of bias was evaluated using the SYRCLE tool. Mortality, hatching, malformations, LC50/EC50 values, mechanistic endpoints, and nanoparticle-characterization data were extracted while accounting for statistical dependence among shared-control comparisons. Three independent studies provided LC50 estimates with numerical 95% confidence intervals on a common mg ZnO/L basis (1.793, 13.8, and 60.0 mg/L). Extreme between-study heterogeneity (I² = 99.6%) precluded presenting a pooled LC50 as a primary result. Hatching impairment and developmental abnormalities were repeatedly observed, although heterogeneous endpoint definitions and reporting formats prevented defensible cross-study pooling. Controlled within-study evidence indicated that surface chemistry and environmental transformation strongly modified toxicity. Zn2+ dissolution, aggregation and hydrodynamic behavior, exposure medium, chorion status, developmental stage, and particle size also influenced effective exposure and biological responses. Overall, ZnO NP developmental toxicity is context dependent and reflects interactions between dynamic particle properties, environmental transformations, and organismal exposure conditions. Standardized characterization in the actual exposure medium, comparable developmental endpoints, and improved quantitative reporting are needed to strengthen mechanistic interpretation and future dependence-aware meta-analysis.

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