Beta Testing

Titanium Dioxide

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Potential Risk IndexTM:


About:

Functions :
1. Colorant – Pigments or dyes that are added in order to change or enhance the color.
2. Fragrance / Fragrance Component – Provides or enhances a particular smell or odor.
3. Opacifier – Makes the mixture less transparent or translucent
4. Sunscreen – Physical sunscreens work by deflecting or scattering UV rays. Chemical sunscreens work by absorbing and dissipating the UV rays as heat.

Titanium dioxide (E number 171), also known as titanium(IV) oxide or titania, is the naturally occurring oxide of titanium. It accounts for 70% of the total production volume of pigments worldwide and widely used to provide whiteness and opacity to products. Therefore, it is also called titanium white, Pigment White 6 (PW6), or CI 77891. [1]

When used in food applications, it whitens skim milk and adds flavors to soups, beer, and nuts. The National Cancer Institute based in the US tested titanium dioxide for carcinogenicity via the oral route and concluded that it is non-carcinogenic. In EU, it is approved to use as food and cosmetics colorants. In US, it can be used as color additives and exempt from certification and permanently listed for food, drugs, cosmetics and medical devices use. It is also used in cosmetic and skin care products, and it is present in almost every sunblock, where it helps protect the skin from ultraviolet light and considered to be less harmful to coral reefs. [1]

Titanium dioxide (TiO2) in USA is safe for use as a physical sunscreen ingredient.
Physical sunscreens typically work by reflecting and scattering UV rays from the sun.

Recent Findings :
Due to limited experiments focusing on skin-particle-light physicochemical interactions of titanium dioxide and its nanoparticles (TiO2 NPs, <100nm), the effects of NP aggregation in the skin remains controversial. Silicon-based coatings on NPs may reduce the supposed toxic effects. [2][3] They can also be labelled as "microfine" TiO2 with an average particle size of 20nm. Preliminary experiments have shown that "microfine TiO2 penetrates deeper into human skin from an oily dispersion than from an aqueous one". [4] Although it is possible to create oil-in-water emulsions to limit excessive penetration of TiO2 into the skin, stability issues arise after only 4 months of storage. [4]
The nanosized formulation "resolved the problem of the unsightly white film of traditional sunscreens and created a vehicle that is more transparent, less viscous, and blends into the skin more easily". [5]

Toxicity from titanium dioxide mainly comes from its possibility of inducing oxidative stress in white blood cells and multiple studies have indicated that there is significant penetration of TiO2 through an intact epidermis, especially in the nanoparticle form. [3][6] It is possible that the induced oxidative stress may lead to DNA damage. [7] [8] TiO2 NPs has also shown to cause "disruption" in the human gastrointestinal tract which may reduce the absorption of other nutrients. [9] TiO2 may also worsen those who already suffer from colorectal cancer and "could enhance tumor formation in colitis-associated cancer". [10] The unreactivity and small size of TiO2 particles may cause it to be trapped in between body cells, disrupting their usual functions. At worst, it has the potential to exacerbate cells which are already cancerous or cause stress to the cell itself resulting in DNA damage.

TiO2 NPs show minimal toxic potential for aquatic species and the environment and even acts as a catalyst to help plants promote photosynthesis and nitrogen metabolism. [12] [13] In vitro studies on isolated pig skin showed no penetration of zinc oxide or TiO2 after 24 h. [14] However, in vivo studies after 30 days showed TiO2 NPs (4-60 nm) deep within the skin and after 60 days, showed diverse penetration in several major organs, including the brain. [14] The study concluded that the lesions found to correlate more directly with the oxidative stress induced by nanoparticles rather than TiO2 itself. [14] TiO2 NPs shows varying degrees of toxicity for different species. It is also hypothesized in many reviews that the toxicity may originate from the nanoparticle structure rather than an intrinsic chemical property of TiO2.

To summarize, titanium dioxide is the principal white pigment used commercially, due to its high refractive index, its ease of dispersion into a variety of matrices, and can be used a whitening agent, or an opacifier. Nanoparticles of titanium dioxide may be able to be absorbed through the skin after chronic application. [7] Though a review on the properties of nanoparticles showed that they are generally considered to be "low risk": "Summarizing published data metal oxides NPs are generally very stable, do not release metal ions and can be considered as having low risk of skin penetration or permeation, which is possible only for those sized <10 nm". [15] "skin penetration depends on particle size is often taken as a rule: particles below 3 µm diameter can penetrate the [skin] through the intercellular pathway; particles between 3 and 10 µm accumulate preferentially in the [hair glands]; and particles above 10 µm do not penetrate the skin". [16]
Nanoparticle properties will not be a contributing factor to the rating of titanium dioxide to ensure objectivity. Although TiO2 is listed in the IARC, their analysis of the compound mostly pertains to inhale rather than contact.

Scientific References :
1. PubChem: https://pubchem.ncbi.nlm.nih.gov/compound/26042

2. Dermal Absorption of Nanomaterials Titanium Dioxide and Zinc Oxide Based Sunscreen (The Danish Environmental Protection Agency, 2015, ISBN: 978-87-93352-53-7)

3. Titanium Dioxide Nanoparticle Penetration into the Skin and Effects on HaCaT Cells. (Int J Environ Res Public Health. 2015 Aug 7;12(8):9282-97. DOI: 10.3390/ijerph120809282.)

4. Skin penetration and stabilization of formulations containing microfine titanium dioxide as physical UV filter. (Int. J. Cosmet. Sci., 22(4), 271–283. doi:10.1046/j.1467-2494.2000.00009.x)

5. The safety of nanosized particles in titanium dioxide– and zinc oxide–based sunscreens. (J. Am. Acad. Dermatol., 61(4), 685–692. doi:10.1016/j.jaad.2009.02.051)

6. Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety and effectiveness (Nanotechnol Sci Appl. 2011; 4: 95–112. Published online 2011 Oct 13. DOI: 10.2147/NSA.S19419)

7. Titanium dioxide in our everyday life; is it safe? (Radiol Oncol. 2011 Dec; 45(4): 227–247. Published online 2011 Nov 16. DOI: 10.2478/v10019-011-0037-0)

8. An in vitro blood culture for evaluating the genotoxicity of titanium dioxide: the responses of antioxidant enzymes. (Toxicol. Ind. Health, 23(1), 19–23. doi:10.1177/0748233707076764)

9. Food grade titanium dioxide disrupts intestinal brush border microvilli in vitro independent of sedimentation. (Cell Biol. Toxicol., 30(3), 169–188. doi:10.1007/s10565-014-9278-1)

10. Food-grade titanium dioxide exposure exacerbates tumor formation in colitis associated cancer model. (Food Chem. Toxicol., 93, 20–31. doi:10.1016/j.fct.2016.04.014)

11. Aggregation and toxicity of titanium dioxide nanoparticles in aquatic environment—A Review. (J. Environ. Sci. Heal. A., 44(14), 1485–1495. DOI:10.1080/10934520903263231)

12. Toxicity of titanium dioxide nanoparticles to rainbow trout (Oncorhynchus mykiss): Gill injury, oxidative stress, and other physiological effects. (Aquat. Toxicol., 84(4), 415–430. DOI:10.1016/j.aquatox.2007.07.009)

13. The in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin. (Toxicol. In Vitro, 20(3), 301–307. DOI:10.1016/j.tiv.2005.08.008)

14. Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure. (Toxicol. Lett., 191(1), 1–8. doi:10.1016/j.toxlet.2009.05.020)

15. Nanoparticles skin absorption: New aspects for a safety profile evaluation. (Regul. Toxicol. Pharmacol., 72(2), 310–322. doi:10.1016/j.yrtph.2015.05.005)

16. Nanoparticles through the skin: managing conflicting results of inorganic and organic particles in cosmetics and pharmaceutics. (Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 3(5), 463–478. doi:10.1002/wnan.146)

17. Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats. (Arch. Toxicol., 82(3), 151–157. DOI:10.1007/s00204-007-0253-y)

18. Titanium Dioxide Nanoparticles in Food and Personal Care Products. (Environ. Sci. Technol., 46(4), 2242–2250. DOI:10.1021/es204168d)

19. In vivoacute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection. (J. Appl. Toxicol., 29(4), 330–337. DOI:10.1002/jat.1414)

20. Titanium Dioxide Nanoparticles Induce DNA Damage and Genetic Instability In vivo in Mice. (Cancer Res., 69(22), 8784–8789. DOI:10.1158/0008-5472.can-09-2496)

21. Enhanced bioaccumulation of cadmium in carp in the presence of titanium dioxide nanoparticles. (Chemosphere, 67(1), 160–166. DOI:10.1016/j.chemosphere.2006.09.003)

22. Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. (Toxicol. Lett., 168(2), 176–185. DOI:10.1016/j.toxlet.2006.12.001)

23. Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure. (Toxicol. Lett., 191(1), 1–8. DOI:10.1016/j.toxlet.2009.05.020)

24. Spleen injury and apoptotic pathway in mice caused by titanium dioxide nanoparticules. (Toxicol. Lett., 195(2-3), 161–168. DOI:10.1016/j.toxlet.2010.03.1116)

25. Daphnia Magna Mortality when Exposed to Titanium Dioxide and Fullerene (C60) Nanoparticles.(Environ. Toxicol. Chem., 25(4), 1132. DOI:10.1897/05-278r.1)

26. Toxicity and interaction of titanium dioxide nanoparticles with microtubule protein. (Acta Biochim. Biophys. Sin., 40(9), 777–782. DOI:10.1093/abbs/40.9.777)

27. Titanium dioxide in our everyday life; is it safe? (Radiat. Oncol., 45(4). DOI:10.2478/v10019-011-0037-0)

28. TiO2 Nanoparticles Induce Dysfunction and Activation of Human Endothelial Cells. (Chem. Res. Toxicol., 25(4), 920–930. DOI:10.1021/tx200551u)

29. Identification of titanium in human tissues: Probable role in pathologic processes. (Hum. Pathol., 22(5), 450–454. DOI:10.1016/0046-8177(91)90130-h)

30. Massive pulmonary deposition of rutile after titanium dioxide exposure: Light-microscopical and physico-analytical methods in pigment identification (Acta. Pathol. Microbiol. Scand. A. 1981 Nov;89(6):455-61.)

31. Titanium Dioxide Deposition and Adenocarcinoma of the Lung (Pathol. Int., 36(5), 783–790. DOI:10.1111/j.1440-1827.1986.tb01066.x)

Regulatory References :
1. WHO International Agency for Research on Cancer (IARC) – Group 2B [2018]

2. EU Scientific Committee on Consumer Safety
https://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_136.pdf

3. EU CosIng Annex IV, COLORANTS ALLOWED IN COSMETIC PRODUCTS [2017]
– Ref: IV/143

4. EU CosIng Annex VI, LIST OF UV FILTERS ALLOWED IN COSMETIC PRODUCTS [2017]
– Ref: VI/27, VI/27a

5. US FDA Color Additives Status List [2015]
– §73.575

6. EU Community Research and Development Information Service
https://cordis.europa.eu/project/rcn/67162/brief/en

7. EU Approved Food Additive [2018]
– E171

8. International Fragrance Association Transparency List [2015]


Safety and Hazards (UN GHS):

1. Harmful if swallowed (H302)
2. Causes skin irritation (H315)
3. Causes serious eye irritation (H319)
4. Harmful if inhaled (H332)
5. May cause respiratory irritation (H335)
6. Suspected of causing cancer (H351)
7. Causes damage to organs through prolonged or repeated exposure (H372)
8. May cause long lasting harmful effects to aquatic life (H413)

Potential Health Concerns For:

1. Arrhythmias, Cardiac ( PubMed ID:25487314 )
2. Blood Platelet Disorders ( PubMed ID:28646487 )
3. Body Weight ( PubMed ID:23131501 )
4. Bronchial Hyperreactivity ( PubMed ID:25456268 )
5. Cell Transformation, Neoplastic ( PubMed ID:19695278 )
6. Chemical and Drug Induced Liver Injury ( PubMed ID:19156710 )
7. Chromosomal Instability ( PubMed ID:19695278 )
8. Congenital Abnormalities ( PubMed ID:25703175 )
9. Diabetes Mellitus, Type 2 ( PubMed ID:29792697 )
10. Feeding and Eating Disorders ( PubMed ID:19156710 )
11. Fetal Death ( PubMed ID:22005274 )
12. Fibrosis ( PubMed ID:25406100 )
13. Heart Injuries ( PubMed ID:28780322 )
14. Heavy Metal Poisoning ( PubMed ID:20863874 )
15. Hypersensitivity ( PubMed ID:30626778 )
16. Hypokinesia ( PubMed ID:25703175 )
17. Infertility, Female ( PubMed ID:22005274 )
18. Infertility, Male ( PubMed ID:24241477 )
19. Inflammation ( PubMed ID:21259345 )
20. Kidney Diseases ( PubMed ID:25406100 )
21. Lethargy ( PubMed ID:19156710 )
22. Leukocytosis ( PubMed ID:19875681 )
23. Liver Cirrhosis ( PubMed ID:19156710 )
24. Liver Diseases ( PubMed ID:19501137 )
25. Lung Diseases ( PubMed ID:19875681 )
26. Lung Injury ( PubMed ID:23409001 )
27. Micronuclei, Chromosome-Defective ( PubMed ID:23111874 )
28. Microsatellite Instability ( PubMed ID:19429261 )
29. Movement Disorders ( PubMed ID:22973466 )
30. Necrosis ( PubMed ID:19156710 )
31. Oligospermia ( PubMed ID:28844848 )
32. Ovarian Diseases ( PubMed ID:23131501 )
33. Pneumonia ( PubMed ID:22956629 )
34. Prenatal Exposure Delayed Effects ( PubMed ID:17656681 )
35. Prenatal Injuries ( PubMed ID:22005274 )
36. Pulmonary Edema ( PubMed ID:23409001 )
37. Pulmonary Fibrosis ( PubMed ID:27760801 )
38. Respiratory Hypersensitivity ( PubMed ID:17656681 )
39. Skin Diseases ( PubMed ID:19501137 )
40. Splenic Diseases ( PubMed ID:20381595 )
41. Thrombosis ( PubMed ID:19156710 )
42. Thymus Hyperplasia ( PubMed ID:28646487 )
44. Weight Loss ( PubMed ID:23565150 )

Potential Health Benefits For:

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