The International Agency for Research on Cancer designates titanium dioxide (TiO2) as a carcinogen, largely due to studies that have found increased lung cancers due to inhalation exposure in animals.

Exposure

Titanium dioxide does not penetrate through healthy skin and poses no local or systemic risk to human health from skin exposure. In response to concerns that nano TiO2 might more readily penetrate damaged skin, researchers applied nano-based sunscreens to pigs ears that had been sunburnt. Titanium dioxide did not reach the deeper levels of the skin in the sunburnt tissue

Most concerns for human health arise when titanium dioxide is inhalable or respirable. For TiO2 to be inhaled, particles must be small enough to reach the alveoli (where oxygen exchange happens) of the lungs. Sampling methods have been developed to estimate the airborne mass concentration of respirable particles,

Titanium Dioxide Rutile Tio2 POWDER Titanio Dioxide Pigment

Inhalation & Cancer: The data suggests nanoized titanium dioxide can be inhaled by some mammals, leading to concerns about adverse effects of human inhalation. Existing studies have suggested TiO2 nanoparticles may be more toxic than traditional larger particles of TiO2.

Titanium dioxide is described as fine if it is 100-3,000 nm^{[25],[26],[27]} and ultrafine if it is smaller than 100 nm.^[28] Findings show that commercial pigments contain almost no particles smaller than 100 nm.^[29],[30] Scattering of light by titanium dioxide is maximized in particles that are 200-300 nm in diameter.^[31] Studies have shown that inhalation exposure of TiO2 particles in cosmetics are predominately inhaled as clusters and do not reach the alveoli (the part of the lungs where oxygen is exchanged).^[32] The findings demonstrated that a user would be exposed to nanomaterials that are larger than 1-100 nanometers.^[33]

Studies have found that when exposed to nanoized titanium dioxide (normally smaller than 100 nanometers), rats and mice experience significant lung inflammation^{[34],[35],[36]} and cell mutations.^[37] Some inflammatory responses resolved a few weeks post-exposure.^[38] Other studies have not found increased lung tumor development in rats that inhaled TiO2.^[39],[40]

An inhalation study of pigmentary titanium dioxide particles in rats, mice, and hamsters found that there were significant species differences in pulmonary responses to inhaled particles. Rats developed more severe symptoms of lung damage.^[41]

Toxicological testing of nanomaterials needs to take into account the effects on particle size on the ways that dose is estimated because smaller particles will have greater surface area by volume.^[42]

Work Related Exposure

Human health studies—mostly occupational studies regarding titanium dioxide inhalation—have demonstrated mixed findings regarding cancer.^[43]

Supporting evidence: The most relevant data for assessing the health risk to workers are results from a chronic animal inhalation study with ultrafine titanium dioxide in which a statistically significant increase in adenocarcinomas was observed.^[44],[45]

Conflicting evidence: Several studies have concluded that there is no increase in mortality,^[46] lung inflammatory response,^[47] or carcinogenic effect^[48],[49] associated with workplace exposure and TiO2.