Balancing Discovery and Caution: Regeneration in zebrafish toxicology

Zebrafish (Danio rerio) have emerged as a cornerstone of modern toxicology, providing unique advantages including strong genetic similarity to humans, experimental accessibility, and well-characterized behavioral assays. A defining feature of zebrafish biology is their remarkable regenerative capacity, which enables repair of fins, retina, spinal cord, liver, heart, and even brain regions. This regenerative ability supports important discoveries in developmental and regenerative biology, yet it also presents a limitation for toxicology. Tissue repair and functional recovery may mask persistent damage, obscure toxicant-induced molecular changes, or create the impression of resilience where concealed injury remains. As a result, zebrafish studies may underestimate the long-term consequences of chemical exposures when extrapolated to humans, who possess much more limited regenerative potential. At the same time, insights from zebrafish regeneration can reveal adaptive pathways that inform protective responses and therapeutic development. Recognizing regeneration as both a strength and a limitation is essential. By integrating complementary endpoints and comparative models, the use of zebrafish will continue to provide valuable and contextually grounded insights into toxicological mechanisms and human health risks.