Titanium Dioxide: Toxic or Safe?

By Lori Stryker, B.Sc., B.H.Ec., B.Ed.

Titanium dioxide is the subject of new controversy, yet it is a substance as old as the earth itself. It is one of the top fifty chemicals produced worldwide. It is a white, opaque and naturally- occurring mineral found in two main forms: rutile and anatase. Both forms contain pure titanium dioxide that is bound to impurities. Titanium dioxide is chemically processed to remove these impurities, leaving the pure, white pigment available for use. Titanium dioxide has a variety of uses, as it is odorless and absorbent. This mineral can be found in many products, ranging from paint to food to cosmetics. In cosmetics, it serves several purposes. It is a white pigment, an opacifier and a sunscreen. Concern has arisen from studies that have pointed to titanium dioxide as a carcinogen and photocatalyst, thus creating fear in consumers. But are these claims true? What does the research on these allegations bear out? Would we as consumers benefit from avoiding this mineral to preserve our long-term health?

A carcinogen is a substance that causes a cellular malfunction, causing the cell to become cancerous and thus potentially lethal to the surrounding tissue and ultimately the body as these rapidly growing mutated cells take over. With the surge in cancer rates among all segments of the population, many people are attempting to reduce or eliminate their exposure to carcinogens. Titanium dioxide is regarded as an inert, non-toxic substance by many regulatory bodies such as the MSDS (Material Safety Data Sheets) and others charged with the responsibility of safeguarding the health of occupational workers and public health. The MSDS states that titanium dioxide can cause some lung fibrosis at fifty times the nuisance dust, defined by the US Department of Labor as 15 mg/m cubed (OSHA) or 10 mg/m cubed (ACGIH Threshold Limit Value). Recently, the International Agency for Research on Cancer (IARC) has classified titanium dioxide to be a possible human carcinogen, thus a group 2B carcinogen. In Canada, titanium dioxide is now listed under WHMIS class D2A (carcinogen)as a result of the IARC designation (ccohs.ca). The definition by the IARC for Group 2B possibly carcinogenic to humans is as follows:

"This category is used for agents for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent for which there is inadequate evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals together with supporting evidence from mechanistic and other relevant data may be placed in this group. An agent may be classified in this category solely on the basis of strong evidence from mechanistic and other relevant data." monographs.iarc.fr)

The NIOSH declaration of carcinogenicity in rats is based on a study by Lee, Trochimowicz & Reinhardt, "Pulmonary Response of Rats Exposed to Titanium Dioxide by Inhalation for Two Years" (1985). The authors of this study found that rats chronically exposed to excessive dust loading of 250 mg/m cubed and impaired clearance mechanisms within the rat, for six hours per day, five days per week for two years, developed slight lung tumours. They also noted that the biological relevance of this data to lung tumours in humans is negligible. It is important to note that rats are known to be an extremely sensitive species for developing tumours in the lungs when overloaded with poorly soluble, low toxicity dust particles. Rat lungs process particles very differently compared to larger mammals such as dogs, primates or humans (Warheit, 2004). This sensitivity in the lungs has not been observed in other rodent species such as mice or hamsters (Warheit, 2004), therefore using the rat model to determine carcinogenicity of titanium dioxide in humans can be misleading, as extrapolation of species-specific data to humans is erroneous.

Many organizations and businesses have perpetuated this assessment of the carcinogenicity of titanium dioxide (ewg.org). However, several studies and study reviews have been used to compile the safety disclaimers for the regulations on the permitted use of titanium dioxide. One such study review took place in Rome, 1969 between the World Health Organization and the Food & Agriculture Organization of the United Nations. Cross species analyses were performed and reviewed for possible toxicity of titanium dioxide. The conference concluded that among the following species: rats, dogs, guinea pigs, rabbits, cats and human males, ingestion of titanium dioxide at varying diet percentages and over long periods of time did not cause absorption of this mineral. Titanium dioxide particulates were not detected in the blood, liver, kidney or urine and no adverse effects were noted from its ingestion. The U.S. Food & Drug Administration (2002) allows for its ingestion, external application including the eye area, and considers it a safe substance for public health. Other epidemiological studies showed that workers exposed to titanium dioxide exhibited no statistically significant relationship between such exposure with lung cancer and respiratory disease, although some cases of pulmonary fibrosis did occur. These studies were conducted in industrial settings where the increased exposure puts these individuals more at risk than the average person.

Titanium dioxide is listed as a safe pigment, with no known adverse effects when used in cosmetics, and approved by the FDA when 99% pure. It is not listed as a carcinogen, mutagen, teratogen, comedogen, toxin or as a trigger for contact dermatitis in any other safety regulatory publications beside the NIOSH (Antczak, 2001; Physical & Theoretical Chemical Laboratory, Oxford University respectively), with the exception of the recent IARC designation. It is reasonable to conclude then, that titanium dioxide is not a cancer-causing substance unless exposure is beyond safe limits during manufacturing using this substance. It is considered safe for use in foods, drugs, paints and cosmetics. This does not end the debate, however, as controversy over the safety of one unique form of titanium dioxide still exists.

One form of mineral or mineral extract, including titanium dioxide, that we should be concerned about is ultrafine or nano particles. As technology has advanced, so has its ability to take normal sized particles of minerals and reduce them to sizes never before imagined. While many are praising this new technology, others are warning of its inherent dangers to our bodies. A study by Churg et. al. at the University of British Columbia in their paper "Induction of Fibrogenic Mediators by Fine and Ultrafine Titanium Dioxide in Rat Tracheal Explants" (1999) found that ultrafine particles of the anatase form of titanium dioxide, which are less than 0.1 microns, are pathogenic or disease causing (see Table 1).

Table 1: Measurements of Mineral Pigment Particles
Particle Size	Measurement
Coarse	Less than 10 microns
Fine	Less than 2.5 microns
Ultrafine (nanoparticles)	Less than 0.1 microns or 100 nanometres
etcgroup.org

Table 2: Particle Size and Entry into the Human Body
Nanoparticle Size	Entry Point
70 nanometres	Alveolar surface of lung
50 nanometres	Cells
30 nanometres	Central Nervous System
Less than 20 nanometres	No data yet
etcgroup.org

Kumazawa, et. al. in their study, "Effects of Titanium Ions and Particles on Neutrophil Function and Morphology" concluded that cytotoxicity (danger to the cell) was dependent on the particle size of titanium dioxide. The smaller the particle size, the more toxic it is (see Table 2). This conclusion is relevant to the consumer because of the cosmetics industry's increasing use of micronized pigments in sunscreens and colour cosmetics. Nanoparticles of titanium dioxide are used in sunscreens because they are colourless at that size and still absorb ultraviolet light. Many cosmetic companies are capitalizing on metal oxide nanoparticles. We have seen, however, that if titanium dioxide particles used to act as a sunscreen are small enough, they can penetrate the cells, leading to photocatalysis within the cell, causing DNA damage after exposure to sunlight (Powell, et. al. 1996) The fear is that this could lead to cancer in the skin. Studies with subjects who applied sunscreens with micronized titanium dioxide daily for 2-4 weeks showed that the skin can absorb microfine particles. These particles were seen in the percutaneous layers of the skin under UV light. Coarse or fine particles of titanium dioxide are safe and effective at deflecting and absorbing UV light, protecting the skin, but consumers should avoid using products with micronized mineral pigments, either in sunscreens or colour cosmetics.

As with any health issue, relevant studies must be examined closely to reach balanced conclusions about its impact on our health and well-being. Often, risk determinations are made without considering actual hazards and real-life exposures (Warheit, 2004). The Organic Make-up Company considers fine or coarse particle sized titanium dioxide and other mineral pigments to be safe according to the studies available and information discussed in this article. Despite repeated requests for micronized pigments in our colour cosmetics, we insist on using only coarse or fine particles of mineral pigments, balancing our need to look beautiful with our more pressing need to stay healthy. With the multitude of cosmetics and chemicals available to us, it is in our best interest to become informed as consumers and make pure, natural and simple choices to protect our health and longevity.

Updated April 30, 2013

References:

• Antczak, Cosmetics Unmasked. Harper Collins; London:2001
• Blake, et.al. "Application of the Photocatalytic Chemistry of TiO2 to Disinfection and the Killing of Cancer Cells", Separation and Purification Methods; Vol 28 (1) 1999 p.1-50
• Churg, Gilks, Dai, UBC Dept. of Pathology. Am J Physiol Lung Cell Mol Physiol. Vol 277 Issue 5 L975-L982, 1999
• Dunford, et. al. FEBS Letters 418, 87 1997
• Etcgroup.org
• Kamazawa, et.al. "Effects of Titanium Ions and Particles of Neutrophil Function and Morphology". Biomaterials 2002 Sep 23 (17): 3757-64
• Powell, et. al. GUT 38, 390 1996
• Warheit, David "Nanoparticles: Health Impacts?". Materials Today, Feb. 2004
• Witt, Stephen. Director of Technological Support, N. American Refractories Co.
• http://www.ccohs.ca/headlines/text186.html
• http://monographs.iarc.fr/ENG/Preamble/CurrentPreamble.pdf