The long-term oral exposure to titanium dioxide impaired immune functions and triggered cytotoxic and genotoxic impacts in rats

Abstract

Background: Titanium dioxide "TiO₂, E171″ is a widely used food additive that exists in various everyday food products all over the world together with vast applications in cosmetics and industry. However, many toxicological aspects particularly following oral exposure still unclear.

Methods: Hence, this study was planned to examine the effect of oral exposure of male Wistar rats to two doses of TiO₂ (20 or 40 mg/kg b.wt.) through oral gavage once daily for 90 consecutive days on the blood components, immunity, cytotoxic, and genotoxic indicators.

Results: A dose-dependent leukopenia, eosinophilia, neutrophilia, and thrombocytopenia were noted. Also, the immunoglobins G (IgG) and IgM were significantly elevated in TiO₂ treated rats. The phagocytic activities, lysozyme, nitric oxide, and immunoglobulin levels were significantly depleted following TiO₂ exposure. A significantly reduced lymphocyte proliferation but elevated LDH activity was prominent in TiO₂ treated rats. Different pathological perturbations were observed in both splenic tissue and bone marrow. A marked increase in CD4⁺ and CD8⁺ immunolabeling was evident. A significant increase in the comet variables was recorded in response to the exposure of rats to the increasing level of TiO₂ at both levels.

Conclusion: Overall, these results indicated that TiO₂ could induce hematotoxicity, genotoxic, and immunotoxic alterations with exposure for long durations.

Keywords: Bone marrow; Hematology; Immune function; Spleen; Titanium dioxide; comet.