Machine Learning Prediction Models of Beneficial and Toxicological Effects of Zinc Oxide Nanoparticles in Rat Feed

Nanoparticles have found widespread application across diverse fields, including agriculture and animal husbandry. However, a persistent challenge in laboratory-based studies involving nanoparticle exposure is the limited availability of experimental data, which constrains the robustness and generalizability of findings. This study presents a comprehensive analysis of the impact of zinc oxide nanoparticles (ZnO NPs) in feed on elemental homeostasis in male Wistar rats. Using correlation-based network analysis, a correlation graph weight value of 15.44 and a newly proposed weighted importance score of 1.319 were calculated, indicating that a dose of 3.1 mg/kg represents an optimal balance between efficacy and physiological stability. To address the issue of limited sample size, synthetic data generation was performed using generative adversarial networks, enabling data augmentation while preserving the statistical characteristics of the original dataset. Machine learning models based on fully connected neural networks and kernel ridge regression, enhanced with a custom loss function, were developed and evaluated. These models demonstrated strong predictive performance across a ZnO NP concentration range of 1–150 mg/kg, accurately capturing the dependencies of essential element, protein, and enzyme levels in blood on nanoparticle dosage. Notably, the presence of toxic elements and some other elements at ultra-low concentrations exhibited non-random patterns, suggesting potential systemic responses or early indicators of nanoparticle-induced perturbations and probable inability of synthetic data to capture the true dynamics. The integration of machine learning with synthetic data expansion provides a promising approach for analyzing complex biological responses in data-scarce experimental settings, contributing to the safer and more effective application of nanoparticles in animal nutrition.