Route-dependent systemic and local immune effects following exposure to solutions prepared from titanium dioxide nanoparticles

Nanoparticle titanium dioxide (nano-TiO2) is a white pigment widely used in foods, sunscreens, and other cosmetic products. However, it remains unclear whether exposure to nano-TiO2 results in immunosuppressive effects or induces a contact hypersensitivity response. To address these data gaps, studies were conducted with the hypothesis that nano-TiO2 exposure could alter immune responses. After 28 days of oral gavage, nano-TiO2 (1.25-250 mg/kg in 0.5% methylcellulose) produced no significant effects on innate, humoral, or cell-mediated immune functions in female B6C3F1 mice. Furthermore, there were no effects on the weights of selected organs (spleen, thymus, liver, lung, and kidneys with adrenals). Following dermal exposure on the ears for 3 days, nano-TiO2 (2.5-10% w/v in 4: 1 acetone: olive oil) did not affect auricular lymph node cell proliferation, although an irritancy response was observed following treatment with 5% and 10% nano-TiO2. Dermal sensitization (2.5-10%) on the back and subsequent challenge (10%) on the right ear with nano-TiO2 produced no significant effects on percentage ear swelling in the Mouse Ear Swelling Test (MEST). However, when nano-TiO2 was injected subcutaneously along the mid-line on top of the head at 125-250 mg/kg (in 0.5% methylcellulose), significant increases in auricular lymph node cell proliferation resulted. These results demonstrate that immune effects of nano-TiO2 exposure are route-of-exposure dependent, and they suggest that irritancy and/or potential hypersensitivity responses may occur following parenteral exposure or dermal administration of nano-TiO2 to compromised skin.