Evaluation of the Toxicity of Titanium Dioxide Nanoparticles Administered by Oral Gavage to Sprague–Dawley Rats on 94 Days of Repeated Dosing

By observing the possible toxic reactions and deaths of titanium dioxide nanoparticles given by oral gavage to Sprague–Dawley (SD) rats at 2, 10, and 50 mg/kg once a day for 94 consecutive days due to accumulation, as well as the recovery of the drug for 30 days after stopping the administration of the drug, we identified the possible target organs of the toxic reactions and determined the dose of its non-toxic reaction in SD rats, in order to provide reference information for evaluating the clinical use of titanium dioxide nanoparticles and the safety of the drug. The results showed that there was no significant abnormality in body weight gain or food intake in all groups of animals during the administration period or the recovery period after drug withdrawal. Hematology, blood biochemistry, and urine indicators did not exceed the normal range, and there was no obvious toxicity. Meanwhile, when analyzed together with the histopathological results, the vital organs such as the heart, liver, lungs, kidneys, spleen, and brain did not show any obvious lesions related to the test substance. No obvious local toxicity lesions were observed in the buccal region of the mouth or the mucous membrane of the tongue at the site of drug administration. In conclusion, the non-toxic dose of titanium dioxide nanoparticles by oral gavage for 94 days in SD rats under the conditions of this test was initially determined to be 50 mg/kg/day.