Exposure to nano titanium dioxide could up cancer risk, says study
By Katie Bird , 18-Nov-2009
Related topics: Formulation & Science
There may be a potential risk of cancer and genetic disorders for individuals working with high concentrations of titanium dioxide nanoparticles, according to US scientists.
The researchers at the University of California, Los Angeles, arrived at this conclusion following a mouse study that suggested ingestion of the nanoparticles led to genetic damage.
In addition to warning against occupational exposure, the study, published in the journal of Cancer Research, warns against the ingestion of food colours, vitamins and non essential drug additives that contain titanium dioxide nanoparticles.
One of the study’s authors Dr Robert Schiestl also advised against using spray-on sunscreens as these could lead to the inhalation of titanium dioxide nanoparticles that are often used to improve the UV protection provided by the products.
Sticking to sun protection products in cream or lotion form is preferable as the nanoparticles don’t cross the skin barrier, according to Schiestl.
The UCLA study looked at the effects of feeding mice titanium dioxide nanoparticles in their daily water supply for a period of five days for adult males, and ten days for pregnant females from day 8.5 to day 18.5 post coitum.
Effects on the DNA and genetic material of the mice were observed to investigate whether ingesting the nanoparticles was genotoxic, led to DNA damage and brought on an inflammatory response within the organism.
According to the study, exposure to titanium dioxide nanoparticles leads to double strand DNA breaks in the mice, in a dose dependent manner – the higher the dose of titanium dioxide the higher the number of double strand breaks.
The double strand DNA breaks are particularly important in a health context as they are more damaging than single strand breaks or oxidative damage, which are transient, according to the authors.
In pregnant females, exposure to the nanoparticles induced significantly more DNA deletions in their offspring than those not exposed.
Inflammatory mechanism
The team also found higher concentrations of markers of inflammation and oxidative stress in the mice that had been exposed to the titanium dioxide nanoparticles, which led the researchers to suggest the toxicity of the particles could be due to their ability to elicit an inflammatory response.
Explaining the potential mechanism, Schiestl said in a statement: “The novel principle is that titanium by itself is chemically inert. However, when the particles become progressively smaller, their surface, in turn, becomes progressively bigger and in the interaction of this surface with the environment, oxidative stress is induced.”
Further human studies are needed in order to truly understand the health effects of titanium dioxide nanoparticles, but the researchers feel the data suggests we should be ‘concerned’ about cancer or genetic disorders for those working with the material and that it would be ‘prudent’ to limit the ingestion of the materials.
“It could be that a certain portion of spontaneous cancers are due to this exposure. And some people could be more sensitive to nanoparticles exposure than others. I believe the toxicity of these nanoparticles has not been studied enough,” added Schiestl.
Source: Journal of Cancer Research
2009, volume 69, issue 22
Titanium Dioxide Nanoparticles Induce DNA Damage and Genetic Instability in vivo in Mice
Benedicte Trouiller, Ramune Reliene, Aya Westbrook, Parrisa Solaimani, Robert H. Schiestl
Pigment
Titanium dioxide is the most widely used white pigment because of its brightness and very high refractive index (n = 2.7), in which it is surpassed only by a few other materials. Approximately 4 million tons of pigmentary TiO2 are consumed annually worldwide. When deposited as a thin film, its refractive index and colour make it an excellent reflective optical coating for dielectric mirrors and some gemstones, for example “mystic fire topaz“. TiO2 is also an effective opacifier in powder form, where it is employed as a pigment to provide whiteness and opacity to products such as paints, coatings, plastics, papers, inks, foods, medicines (i.e. pills and tablets) as well as most toothpastes. Opacity is improved by optimal sizing of the titanium dioxide particles.
Used as a white food colouring, it has E number E171. Titanium dioxide is often used to whiten skimmed milk; this has been shown statistically to increase skimmed milk’s palatability.[14]
In cosmetic and skin care products, titanium dioxide is used both as a pigment and a thickener. It is also used as a tattoo pigment and styptic pencils.
This pigment is used extensively in plastics and other applications for its UV resistant properties where it acts as a UV absorber, efficiently transforming destructive UV light energy into heat.
In ceramic glazes titanium dioxide acts as an opacifier and seeds crystal formation.
In almost every sunscreen with a physical blocker, titanium dioxide is found because of its high refractive index, its strong UV light absorbing capabilities and its resistance to discolouration under ultraviolet light. This advantage enhances its stability and ability to protect the skin from ultraviolet light. Sunscreens designed for infants or people with sensitive skin are often based on titanium dioxide and/or zinc oxide, as these mineral UV blockers are believed to cause less likely skin irritation than chemical UV absorber ingredients. The titanium dioxide particles used in sunscreens have to be coated with silica or alumina, because titanium dioxide creates radicals in the photo catalytic reaction. These radicals are carcinogenic, and could damage the skin.
Titanium dioxide is used to mark the white lines on the tennis courts of the All England Lawn Tennis and Croquet Club, best known as the venue for the annual grand slam tennis tournament The Championships, Wimbledon.
As a photocatalyst
Titanium dioxide, particularly in the anatase form, is a photocatalyst under ultraviolet light. Recently it has been found that titanium dioxide, when spiked with nitrogen ions, or doped with metal oxide like tungsten trioxide, is also a photocatalyst under visible and UV light. The strong oxidative potential of the positive holes oxidizes water to create hydroxyl radicals. It can also oxidize oxygen or organic materials directly. Titanium dioxide is thus added to paints, cements, windows, tiles, or other products for sterilizing, deodorizing and anti-fouling properties and is also used as a hydrolysis catalyst. It is also used in the Graetzel cell, a type of chemical solar cell.
The photocatalytic properties of titanium dioxide were discovered by Akira Fujishima in 1967[15] and published in 1972.[16] The process on the surface of the titanium dioxide was called the Honda-Fujishima effect.[15] Titanium dioxide has potential for use in energy production: as a photocatalyst, it can
- carry out hydrolysis; i.e., break water into hydrogen and oxygen. Were the hydrogen collected, it could be used as a fuel. The efficiency of this process can be greatly improved by doping the oxide with carbon.[17].
- Titanium dioxide can also produce electricity when in nanoparticle form. Research suggests that by using these nanoparticles to form the pixels of a screen, they generate electricity when transparent and under the influence of light. If subjected to electricity on the other hand, the nanoparticles blacken, forming the basic characteristics of a LCD screen. According to creator Zoran Radivojevic, Nokia has already built a functional 200-by-200-pixel monochromatic screen which is energetically self-sufficient.
In 1995 Fujishima and his group discovered the superhydrophilicity phenomenon for titanium dioxide coated glass exposed to sun light.[15] This resulted in the development of self-cleaning glass and anti-fogging coatings.
TiO2 incorporated into outdoor building materials, such as paving stones in noxer blocks or paints, can substantially reduce concentrations of airborne pollutants such as volatile organic compounds and nitrogen oxides.[18]
A photocatalytic cement that uses titanium dioxide as a primary component, produced by Italcementi Group, was included in Time’s Top 50 Inventions of 2008.[19]
TiO2 offers great potential as an industrial technology for detoxification or remediation of wastewater due to several factors.
- The process occurs under ambient conditions very slowly, direct UV light exposure increases the rate of reaction.
- The formation of photocyclized intermediate products, unlike direct photolysis techniques, is avoided.
- Oxidation of the substrates to CO2 is complete.
- The photocatalyst is inexpensive and has a high turnover.
- TiO2 can be supported on suitable reactor substrates.
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). The ACGIH states that titanium dioxide is “not classifiable as a human carcinogen”. Symptoms of chronic overexposure to titanium dioxide in an industrial setting, according to the MSDS, include a “slight increase in lung tumour incidence in lab rats”. It also states “when titanium dioxide was fed to rats/mice in a carcinogen bioassay, it was not carcinogenic”. The NIOSH declares that at 5000 mg/m cubed there was slight lung fibrosis, concluding that this substance was carcinogenic in rats.
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. 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). It is reasonable to conclude then, that titanium dioxide is not a cancer-causing substance and is generally 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 Co. 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.
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.
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