Four-week Repeated Oral Dose Toxicity Study of Zinc Maltol in Male Rats

Abstract

[Purpose] Zinc (Zn) is trace element which is essential for life, and Zn deficiency causes adverse effects like dysgeusia. To deal with this, Zn supplement with Zn complex is commonly used. Zinc complex is also reported to have pharmacological effects such as antioxidant activity and liver protection. On the other hand, it is known that excessive Zn intake causes toxicities like pancreatic toxicity, and thus there is a possibility that excessive Zn supplement by Zn complex induces some toxicities. However, the toxicity information is unclear due to few studies for Zn complex. Therefore, Zinc maltol (ZM), which is a typical Zn complex, was administered orally to male rats for 4 weeks to assess the toxicities in the present study. [Method] ZM was administered orally to male SD rats for 4 weeks at a dose of 0, 200, 600 or 1000 mg/kg/day (5 animals per group) to assess the toxicities. [Results and Discussion] At 1000 mg/kg/day, pancreatitis-like histopathological changes and increases in white blood cell parameters and creatine kinase were observed. Decrease in red blood cell parameters and extramedullary hematopoiesis in spleen were observed. In addition, low plasma iron and copper concentration were observed. Given these results, it is judged that ZM induced pancreatitis and anemia at a dose of 1000 mg/kg/day by 4-week repeated oral administration in male rats. The no-observable-adverse-effect-level (NOAEL) of ZM was judged to be 600 mg/kg/day in male rats under the present study conditions.