Titanium Dioxide

Titanium dioxide (TiO2) is used in a variety of personal care products, including sunscreens, pressed powders, and loose powders, as a UV filter or whitening agent. In lotions and creams, it presents low risk of exposure. However, when TiO2 is inhalable—as it may be in powders—it is considered a possible carcinogen by the International Agency for Research on Cancer.[1] Nanoized TiO2 does not appear to confer any unique health hazards.

FOUND IN: Sunscreen, pressed and loose powders

WHAT TO LOOK FOR ON THE LABEL: Titanium dioxide, TiO2

WHAT IS TITANIUM DIOXIDE? TiO2 is a fine white powder that occurs naturally. It was first intentionally produced for use as a white pigment in 1923.[2]

It is naturally opaque and bright, which makes it useful for use in paper, ceramics, rubber, textiles, paints and cosmetics.[3] It is also UV-resistant, and is used widely in sunscreens and pigments that are likely to be exposed to light. It is used in a wide variety of personal care products, including color cosmetics such as eye shadow and blush, loose and pressed powders and in sunscreens.

TiO2 can form several different shapes, which have different properties. Some shapes can be converted to nanomaterials. Micronized TiO2 (also called “nano”) was introduced in the early 1990s.[4] Nanotechnology and micronization both refer to the practice of creating very small particles sizes of a given material. Nano usually refers to particles smaller than 100 nanometers; a nanometer is 1/1 billionth of a meter. At these small sizes, and at low concentrations, TiO2 appears transparent, allowing for effective sunscreens that do not appear white.[5]

TiO2 will be listed on product labels, but companies are not required to list ingredient size or structure. When it is used in sunscreens, TiO2 is considered an active ingredient, which means the concentration must also be listed.[6]

HEALTH CONCERNS: The International Agency for Research on Cancer designates TiO2 as a carcinogen, largely due to studies that have found increased lung cancers due to inhalation exposure in animals.[7]

Exposure: TiO2 does not penetrate through healthy skin and poses no local or systemic risk to human health from skin exposure.[8],[9],[10],[11] In response to concerns that nano TiO2 might more readily penetrate damaged skin, researchers applied nano-based sunscreens to pigs ears that had been sunburnt. TiO2 did not reach the deeper levels of the skin in the sunburnt tissue.[12]

Most concerns arise when TiO2 is inhalable or respirable. In order for TiO2 to be inhaled, particles must be small enough to reach the alveoli (where oxygen exchange happens) of the lungs. Sampling methods have been developed to estimate the airborne mass concentration of respirable particles,[13],[14],[15],[16],[17] and inhalable dust[18],[19],[20] [21]

Inhalation & Cancer: The data suggests nanoized TiO2 can be inhaled by some mammals, leading to concerns about human inhalation. Existing studies have suggested TiO2 nanoparticles may be more toxic than traditional larger particles of TiO2.[22],[23],[24]

TiO2 is described as fine if it is 100-3,000 nm[25],[26],[27] and ultrafine if it is smaller than 100 nm.[28] Findings show that commercial pigments contain almost no particles smaller than 100 nm.[29],[30] Scattering of light by TiO2 is maximized in particles that are 200-300 nm in diameter.[31] Studies have shown that inhalation exposure of TiO2 particles in cosmetics are predominately inhaled as clusters and do not reach the alveoli (the part of the lungs where oxygen is exchanged).[32] The findings demonstrated that a user would be exposed to nanomaterials that are larger than 1-100 nanometers.[33]MORE...

Studies have found that when exposed to nanoized TiO2 (normally smaller than 100 nanometers), rats and mice experience significant lung inflammation[34],[35],[36] and cell mutations.[37] Some inflammatory responses resolved a few weeks post-exposure.[38] Other studies have not found increased tumor development in rats that inhaled TiO2. [39],[40]

An inhalation study of pigmentary TiO2 particles in rats, mice, and hamsters found that there were significant species differences in pulmonary responses to inhaled particles. Rats developed more severe symptoms of lung damage.[41]

Toxicological testing of nanomaterials needs to take into account the effects on particle size on the ways that dose is estimated because smaller particles will have greater surface area by volume.[42]

Work Related Exposure

Human studies—mostly occupational studies regarding TiO2 inhalation—have demonstrated mixed findings regarding cancer.[43]

Supporting evidence: The most relevant data for assessing the health risk to workers are results from a chronic animal inhalation study with ultrafine TiO2 in which a statistically significant increase in adenocarcinomas was observed.[44],[45]

Conflicting evidence: Several studies have concluded that there is no increase in mortality,[46] lung inflammatory response,[47] or carcinogenic effect[48],[49] associated with workplace exposure and TiO2.

VULNERABLE POPULATIONS: Everyone

REGULATIONS: The US National Institute for Occupational Health and Safety has set exposure limits for workers due to concerns about lung cancer.[50] The E.U. was the first scientific opinion on the safe use of TiO2 as a UV-filter at a maximum concentration of 25% in cosmetic products was adopted 24 October 2000 by the SCCNFP.[51]

HOW TO AVOID: Avoid loose powders and blushes that contain titanium dioxide. Use caution as well with pressed powders, since they can become airborne when used.

Caveat: TiO2 makes a very effective sunscreen in creams and lotions, and is one of the safest options available. Avoid it only in aerosolized (spray on) sunscreens.

References

[1] IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. (2010). Carbon black, titanium dioxide, and talc. IARC monographs on the evaluation of carcinogenic risks to humans/World Health Organization, International Agency for Research on Cancer93, 1

[2] NIOSH. NIOSH Pocket Guide to Chemical Hazards (2010). Available online: http://www.cdc.gov/niosh/npg/npgd0617.html. September 12, 2014.

[3] IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. (2010). Carbon black, titanium dioxide, and talc. IARC monographs on the evaluation of carcinogenic risks to humans/World Health Organization, International Agency for Research on Cancer93, 1

[4] Schilling, K., Bradford, B., Castelli, D., Dufour, E., Nash, J. F., Pape, W., … & Schellauf, F. (2010). Human safety review of “nano” titanium dioxide and zinc oxide. Photochemical & Photobiological Sciences9(4), 495-509.

[5] Schilling, K., Bradford, B., Castelli, D., Dufour, E., Nash, J. F., Pape, W., … & Schellauf, F. (2010). Human safety review of “nano” titanium dioxide and zinc oxide. Photochemical & Photobiological Sciences9(4), 495-509.

[6] Lewicka ZA, Benedetto AF, Benoit DN, William WY, Fortner JD, Colvin VL. The structure, composition, and dimensions of TiO2 and ZnO nanomaterials in commercial sunscreens. Journal of Nanoparticle Research. 2011 Sep 1;13(9):3607-17.

[7] IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. (2010). Carbon black, titanium dioxide, and talc. IARC monographs on the evaluation of carcinogenic risks to humans/World Health Organization, International Agency for Research on Cancer93, 1

[8] Borm PJ, Robbins D, Haubold S, Kuhlbusch T, Fissan H, Donaldson K et al. The potential risks of nanomaterials: a review carried out for ECETOC, Particle and Fibre Toxicology 2006, 3:11. More information available online: http://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_123.pdf

[9] SCCNFP/0005/98 (Scientific Committee on Cosmetic Products and Non-Food Products) Titanium Dioxide, adopted by the SCCNFP during the 14th plenary meeting of 24 October 2000

[10] Gamer AO, Leibold E, van Ravenzwaay B. The in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin. Toxicol In Vitro. 2006;20(3):301-7.

[11] Lademann J, Weigmann H, Rickmeyer C, Barthelmes H, Schaefer H, Mueller G, et al. Penetration of titanium dioxide microparticles in a sunscreen formulation into the horny layer and the follicular orifice. Skin Pharmacol Appl Skin Physiol 1999;12(5):247-56.

[12] Miquel‐Jeanjean C, Crépel F, Raufast V, Payre B, Datas L, Bessou‐Touya S, Duplan H. Penetration Study of Formulated Nanosized Titanium Dioxide in Models of Damaged and Sun‐Irradiated Skins. Photochemistry and photobiology. 2012 Nov 1;88(6):1513-21.

[13] CEN [1993].Workplace atmospheres—size fraction definitions for measurement of airborne particles, EN 481. Brussels, Belgium: European Committee for Standardization.

[14] ISO [1995]. Air quality—particle size fraction definitions for health-related sampling. Geneva, Switzerland: International Organization for Standardization, ISO Report No. ISO 7708.

[15] ACGIH [1994]. 1994–1995 Threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinnati, OH: Americal Conference of Governmental Industrial Hygenists.

[16] NIOSH [1998]. Particulates not otherwise regulated, respirable. Method 0600 (supplement issued January 15, 1998). In: NIOSH manual of analytical methods. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 94–113 [http://www.cdc.gov/ niosh/nmam/pdfs/0600.pdf].

[17] CDC: Centers for Disease Control and Prevention. Current Intelligence Belletin 63: Occupational exposure to Titanium Dioxide. 2011. Available online: https://www.cdc.gov/niosh/docs/2011-160/pdfs/2011-160.pdf

[18] International Standards Organization (1995). Air Quality Particle Size Fraction Definitions for Health-related Sampling. (ISO Standard 7708), Geneva.

[19] Health and Safety Executive (2000). General Methods for Sampling and Gravimetric Analysis of Respirable and Inhalable Dust: Methods for the Determination of Hazardous Substances: MDHS 14/3. London.

[20] IARC: International Agency for Research on Cancer. IARC Monographs Volume 93. Titanium Dioxide. Pg. 199. Available online: https://monographs.iarc.fr/ENG/Monographs/vol93/mono93-7.pdf

[21] International Standards Organization (1995). Air Quality Particle Size Fraction Definitions for Health-related Sampling. (ISO Standard 7708), Geneva.

[22] Oberdörster G. Pulmonary effects of inhaled ultrafine particles. Int Arch Occup Environ Health 2001; 74(1):1-8.

[23]Blank et al., 2013

[24] Sager TM, Kommineni C, Castranova V. Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of particle surface area. Part Fibre Toxicol 2008; 5: 17.

[25] Lee KP, Trochimowicz HJ, Reinhardt CF [1985]. Pulmonary response of rats exposed to titanium dioxide (TiO2 ) by inhalation for two years. Toxicol Appl Pharmacol 79:179–192.

[26] CDC: Centers for Disease Control and Prevention. Current Intelligence Belletin 63: Occupational exposure to Titanium Dioxide. 2011. Available online: https://www.cdc.gov/niosh/docs/2011-160/pdfs/2011-160.pdf

[27] Aitken RJ, Creely KS, Tran CL [2004]. Nanoparticles: an occupational hygiene review. HSE Research Report 274. United Kingdom: Health & Safety Executive [http://www.hse.gov.uk/research/ rrhtm/rr274.htm].

[28] CDC: Centers for Disease Control and Prevention. Current Intelligence Belletin 63: Occupational exposure to Titanium Dioxide. 2011. Available online: https://www.cdc.gov/niosh/docs/2011-160/pdfs/2011-160.pdf

[29] Braun JH (1997). Titanium dioxide—A review. J Coatings Technol, 69:59–72.

[30] IARC: International Agency for Research on Cancer. IARC Monographs Volume 93. Titanium Dioxide. Available online: https://monographs.iarc.fr/ENG/Monographs/vol93/mono93-7.pdf

[31] IARC: International Agency for Research on Cancer. IARC Monographs Volume 93. Titanium Dioxide. Available online: https://monographs.iarc.fr/ENG/Monographs/vol93/mono93-7.pdf

[32] Nazarenko Y, Zhen H, Han T, Lioy PJ, Mainelis G. Potential for inhalation exposure to engineered nanoparticles from nanotechnology-based cosmetic powders. Environmental health perspectives. 2012 Jun 1;120(6):885.

[33] Nazarenko Y, Zhen H, Han T, Lioy PJ, Mainelis G. Potential for inhalation exposure to engineered nanoparticles from nanotechnology-based cosmetic powders. Environmental health perspectives. 2012 Jun 1;120(6):885.

[34] Ferin J, Oberdoerster G, Penney DP. Pulmonary retention of ultrafine and fine particles in rats. Am J Respir Cell Mol Biol 1992; 6(5):535-42. More information available online: http://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_123.pdf

[35] Grassian VH, O’Shaughnessy PT, Adamcakova-Dodd A, Pettibone JM, Thorne PS. Inhalation exposure study of titanium dioxide nanoparticles with a primary particle size of 2 to 5 nm. Environmental health perspectives. 2007 Mar 1:397-402.

[36] Gurr JR, Wang AS, Chen CH, Jan KY. Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology. 2005 Sep 15;213(1):66-73.

[37] Trouiller B, Reliene R, Westbrook A, Solaimani P, Schiestl RH. Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer research. 2009 Nov 15;69(22):8784-9.

[38] Grassian VH, O’Shaughnessy PT, Adamcakova-Dodd A, Pettibone JM, Thorne PS. Inhalation exposure study of titanium dioxide nanoparticles with a primary particle size of 2 to 5 nm. Environmental health perspectives. 2007 Mar 1:397-402.

[39] Muhle H, Bellmann B, Creutzenberg O, Dasenbrock C, Ernst H, Kilpper R, MacKenzie JC, Morrow P, Mohr U, Takenaka S, Mermelstein R [1991]. Pulmonary response to toner upon chronic inhalation exposure in rats. Fund Appl Toxicol 17:280–299.

[40] CDC: Centers for Disease Control and Prevention. Current Intelligence Belletin 63: Occupational exposure to Titanium Dioxide. 2011. Available online: https://www.cdc.gov/niosh/docs/2011-160/pdfs/2011-160.pdf

[41] Bermudez E, Mangum JB, Asgharian B, Wong BA, Reverdy EE, Janszen DB, Hext PM, Warheit DB, Everitt JI. Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles. Toxicological Sciences. 2002 Nov 1;70(1):86-97.

[42] Schilling, K., Bradford, B., Castelli, D., Dufour, E., Nash, J. F., Pape, W., … & Schellauf, F. (2010). Human safety review of “nano” titanium dioxide and zinc oxide. Photochemical & Photobiological Sciences9(4), 495-509.

[43] IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. (2010). Carbon black, titanium dioxide, and talc. IARC monographs on the evaluation of carcinogenic risks to humans/World Health Organization, International Agency for Research on Cancer93, 1

[44] Heinrich U, Fuhst R, Rittinghausen S, Creutzenberg O, Bellmann B, Koch W, Levsen K [1995]. Chronic inhalation exposure of Wistar rats and two different strains of mice to dieselengine exhaust, carbon black, and titanium dioxide. Inhal Toxicol 7(4):533–556.

[45] CDC: Centers for Disease Control and Prevention. Current Intelligence Belletin 63: Occupational exposure to Titanium Dioxide. 2011. Available online: https://www.cdc.gov/niosh/docs/2011-160/pdfs/2011-160.pdf

[46] Fryzek JP, Chadda B, Marano D, White K, Schweitzer S, McLaughlin JK, Blot WJ. A cohort mortality study among titanium dioxide manufacturing workers in the United States. Journal of occupational and environmental medicine. 2003 Apr 1;45(4):400-9.

[47] Liao CM, Chiang YH, Chio CP. Assessing the airborne titanium dioxide nanoparticle-related exposure hazard at workplace. Journal of hazardous materials. 2009 Feb 15;162(1):57-65.

[48] Hext PM, Tomenson JA, Thompson P. Titanium dioxide: inhalation toxicology and epidemiology. Annals of Occupational Hygiene. 2005 Aug 1;49(6):461-72.

[49] Liao CM, Chiang YH, Chio CP. Model-based assessment for human inhalation exposure risk to airborne nano/fine titanium dioxide particles. Science of the total environment. 2008 Dec 15;407(1):165-77.

[50] OSHA: Occupational Safety & Health Administration. Titanium Dioxide. Available online: https://www.osha.gov/dts/chemicalsampling/data/CH_272100.html

[51] SCCNFP/0005/98 (Scientific Committee on Cosmetic Products and Non-Food Products) Titanium Dioxide, adopted by the SCCNFP during the 14th plenary meeting of 24 October 2000. More information available online: http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_136.pdf