Assessment of Systemic Toxicity, Genotoxicity, and Early Phase Hepatocarcinogenicity of Iron (III)-Tannic Acid Nanoparticles in Rats

Iron-tannic acid nanoparticles (Fe-TA NPs) presented MRI contrast enhancement in both liver cancer cells and preneoplastic rat livers, while also exhibiting an anti-proliferative effect via enhanced autophagic death of liver cancer cells. Hence, a toxicity assessment of Fe-TA NPs was carried out in the present study. Acute and systemic toxicity of intraperitoneal Fe-TA NPs administration was investigated via a single dose of 55 mg/kg body weight (bw). Doses were then repeated 10 times within a range of 0.22 to 5.5 mg/kg bw every 3 days in rats. Furthermore, clastogenicity was assessed by rat liver micronucleus assay. Carcinogenicity was evaluated by medium-term carcinogenicity assay using glutathione S-transferase placental form positive foci as a preneoplastic marker, while three doses ranging from 0.55 to 17.5 mg/kg bw were administered 10 times weekly via intraperitoneum. Our study found that the LD(50) value of Fe-TA NPs was greater than 55 mg/kg bw. Repeated dose administration of Fe-TA NPs over a period of 28 days and 10 weeks revealed no obvious signs of systemic toxicity, clastogenicity, and hepatocarcinogenicity. Furthermore, Fe-TA NPs did not alter liver function or serum iron status, however, increased liver iron content at certain dose in rats. Notably, antioxidant response was observed when a dose of 17.5 mg/kg bw was given to rats. Accordingly, our study found no signs of toxicity, genotoxicity, and early phase hepatocarcinogenicity of Fe-TA NPs in rats.