CSPI says it might reconsider its rating if specifications for food-grade titanium dioxide in the U.S. are updated to ensure nanoparticles are minimized, and new studies are conducted to assess its capacity to cause cancer or other health problems. 

No acute effects of nano-sized TiO₂ were observed in Danio rerio (zebrafish) embryos. Exposure of rainbow trout to TiO₂ NPs triggered lipid peroxidation, influence on the respiratory tract, disturbance in the metabolism of Cu and Zn, induction of intestinal erosion  and accumulation in kidney tissue. Linhua et al. exposed juvenile carp to 100 and 200 mg/ml of particles and TiO₂ observed no mortality. However, the fish suffered from oxidative stress and pathological changes in gill and liver. In the infaunal species Arenicola marina, exposure to TiO₂ NPs in sediment caused sub-lethal effects including decrease in casting rate and increase in cellular and DNA damage. Aggregated particles were visible in the lumen of the gut, but no uptake through the gut or the skin was observed.

Lithopone is a white pigment (PW5) co-precipitated from solutions of zinc and barium salts according to the following reaction: 

In its 2016 opinion, the ANS Panel recommended new studies be carried out to fill the gaps on possible effects on the reproductive system, which could enable them to set an Acceptable Daily Intake (ADI ). Uncertainty around the characterisation of the material used as the food additive (E 171) was also highlighted, in particular with respect to particle size and particle size distribution of titanium dioxide used as E 171.   

In addition to consistency, manufacturers must also consider the cost implications of buff percentage. Higher levels of coating on titanium dioxide particles can increase production costs, as more coating materials are required. However, a lower buff percentage may lead to a lower quality product that does not meet the needs of customers. Balancing the cost and quality considerations of buff percentage is a key challenge for manufacturers in the titanium dioxide industry.

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