Four-week repeated oral dose toxicity study of zinc maltol in rats

Zinc (Zn) is one of the trace elements, and Zn deficiency causes many adverse effects. Zn complexes are used for Zn supplementation, but there are few toxicity reports. Zn maltol (ZM) was orally administered for 4 weeks to male rats at a dose of 0, 200, 600, or 1000 mg/kg to assess its toxicity. As a ligand group, maltol was administered at a dose of 800 mg/kg/day. General conditions, ophthalmology, hematology, blood biochemistry, urinalysis, organ weights, necropsy, histopathology, and plasma Zn concentration were investigated. Plasma Zn concentration increased with dose levels of ZM. The following toxicities were observed at 1000 mg/kg. Pancreatitis was observed with histopathological lesions and increases in white blood cell parameters and creatine kinase. Anemia was observed with changes in red blood cell parameters and extramedullary hematopoiesis in the spleen. Decreases in the trabecula and growth plate in the femur were observed. On the other hand, no toxicities were observed in the ligand group. In conclusion, these toxicities induced by ZM have been reported as Zn-related toxicities. It was considered that these results will be helpful for a creation and development of new Zn complexes as well as supplements.