Research question




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 toTiO2.

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


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


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.