Study	Design	Research question	Sample	Measures	Results
Boffetta et al., 2004	Cohort Study	Is lung cancer mortality related to occupational exposure to TiO₂ NP?	Follow up study on 15,017 workers (14,331 men) in Europe 686 were females	Study on exposed workeh rs in 11 TiO₂ factories in six European Countries to assess mortality and carcinogenicity effects.	There is no carcinogenicity effect to exposed TiO₂ NP workers. The result is statistically significant
Ellis et al., 2010	Cohort Study	Is there an increase in mortality among workers of three Titanium dioxide plants in the United States?	A total of 5054 individuals were sampled at 3 DuPont TiO₂ Plants for over a 40-year period	The mortality experience of the TiO₂ process workers were compared with the US population during follow up	There are no significant increases in the mortality in the cohort relating to TiO₂ exposure which is low compared to US population.
Ling et al., 2011	Mathematical simulation of TiO₂ exposure	Is there an exposure risk to TiO₂ workers?	Review data from other studies to quantify risk exposure toTiO_2.	Applied risk modelling to quantity risk exposure to TiO₂ by workers	Uncertainty because not applied to real situation and admitted biasness in the design
Lai et al., 2008	Experimental - in vitro tests	Does TiO₂ NP exert differential cytotoxic effects on various human cell types?	3 different experiments conducted repeatedly 3 times on human neural cells and fibroblasts.	Cells were exposed to TiO₂ NP for cytotoxicity tests	3 experiments conducted were statistically significant (P < 0.05). Cell necrosis and apoptotic cells were evident which is dose response dependent.
Naya et al., 2012	Experimental In vivo tests	Is there toxicity of TiO₂ through inhalation exposure pathways?	64 male Sprague Dawley rats (7 wks. old) were used	Single instillation of TiO₂ intratracheal, orally, at 1.0 or 5.0 mg/kg body weight .and 0.2 or 1	Results not statistically significant. TiO₂ Anatase nanoparticle crystal forms are not geno toxic following in tracheal instillation in rats.
Osman et al., 2010	Experimental In vitro tests	Is there cytotoxicity and geno toxicity effects of TiO₂ NP to Hep-2 cells?	Human Cell cultures of Hep-2 Cell line	The cells were exposed to various concentrations of TiO₂ NP to observe geno toxicity and cytotoxicity effects	Cytotoxicity and geno toxicity to TiO₂ NP were dose-response depended. Cells exposed were 2 times greater than un exposed cells to TiO₂ regarding geno toxicity.
Srivastava et al., 2013	(Experimental) In vitro tests	Does TiO₂ NP induce oxidative stress and geno toxicity effects on Human lung cancer cells A549?	Human lung cancer cells A549	To measure TiO₂ NP effect on apoptosis, oxidative stress and geno toxicity in human lung cancer cell.	TiO₂-NP exposed cells showed oxidative stress effects promoting ROS (Reactive Oxygen Species), and decrease in catalase and glutathione enzymatic activity. Apoptosis in cells was also observed.
Zhang et al., 2013	(Experimental) In vitro test method	Is there risk of cytotoxicity of mouse macrophages from exposure to various forms of TiO₂ NP?	Mouse Macrophages cells (Ana-1 and MH-S cells)	The cells were exposed to various forms of TiO₂ NP for cytotoxicity effects	Low toxicity in mouse macrophages cells & higher toxicity in Ana-1 cells than MH-S cells.
Grassian et al., 2007	Experimental In vivo-mice whole body exposure 4 hrly	To assess the toxicity of TiO₂ to lung cells	6 weeks old male C57Bl/6 mice, well fed and weigh 22 and 25 g at the time of necropsy	In vivo-mice whole body exposure 4 hrly or sub acutely 4 hr/day for 10 days	Statistically significant to exposure. Mice exposed acutely to 0.77 - 7.22 mg/m³TiO₂ NP demonstrated minimal lung toxicity or inflammation at 0, 1 or 2 weeks after exposure.