Amount: if too little titanium dioxide is added, the distance between particles is too large and there is not enough opacity, while if the titanium content is too high, the particles interfere with each other and poor efficiency is obtained.

Separately, concerns have been raised about titanium dioxide impacting one's genetic code. This can be traced to a 2009 study which found that titanium dioxide nanoparticles caused DNA damage and genetic instability in mice. A 2022 study published in Food and Chemical Toxicology also raised concerns about the DNA-damaging effects of titanium dioxide as a food additive. The study noted that results evidenced a DNA-damaging effect, and added that there may also be impacts to chromosomal integrity, an indicator of cancer risk.

Scientists analyzed research that examined how titanium dioxide nanoparticles interact with the brain for a 2015 review published in Nanoscale Research Letters. The researchers wrote: “Once the TiO2 NPs are translocated into the central nervous system through [certain] pathways, they may accumulate in the brain regions. For their slow elimination rates, those NPs could remain in the brain zones for a long period, and the Ti contents would gradually increase with repeated exposure.” After reviewing dozens of studies, the scientists concluded: “Long-term or chronic exposure to TiO2 nanoparticles could potentially lead to the gradually increased Ti contents in the brain, which may eventually induce impairments on the neurons and glial cells and lead to CNS dysfunction as a consequence.”