Zebrafish: A Cost-Effective Model for Enhanced Forensic Toxicology Capabilities in Low- and Middle-Income Countries

Low- and middle-income countries (LMICs) are increasingly challenged by the rising burden of medicolegal cases. Traditional forensic infrastructure and in vivo rodent models often have significant limitations due to high costs and ethical concerns. As a result, zebrafish (Danio rerio) are gaining popularity as an attractive alternative model for LMICs because of their cost-effectiveness and practical advantages. Zebrafish have a lower acquisition cost, require less demanding husbandry, and have rapid development cycles, all of which facilitate faster and more economical toxicological studies, even in limited laboratory space. Additionally, the optical transparency of zebrafish embryos and larvae allows for non-invasive in vivo observations, reducing the need for extra resources. Research has shown that zebrafish can effectively investigate the behavioral, developmental, and cardiotoxic effects of various novel psychoactive substances (NPSs), including synthetic opioids, cathinones, and hallucinogens. They also excel in metabolic profiling, producing a broader range of metabolites than other models, with significant overlap in human metabolism. The presence of mammalian-like metabolic enzymes further positions zebrafish as a valuable tool for understanding human NPS metabolism and predicting potential effects. Notably, they can identify metabolites that traditional models may not detect, underscoring their potential for novel metabolite discovery. Despite these advantages, standardizing data collection protocols and addressing interlaboratory variability are crucial challenges that must be overcome for the widespread adoption of the zebrafish model. However, ongoing global efforts are paving the way to address these limitations and ensure the successful integration of zebrafish models into the field of forensic toxicology. This review highlights the potential of zebrafish as a cost-effective and versatile model for LMICs, emphasizing their growing application in NPS research and forecasting broader adoption in forensic toxicology.