How Toxic or Safe Titanium Dioxide is as a Sunscreen!

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. 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).

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.

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Heterogeneous photocatalytic degradation of organic contaminants over titanium dioxide: A review of fundamentals, progress and problems

Abstract
Even though heterogeneous photocatalysis appeared in many forms, photodegradation of organic pollutants has recently been the most widely investigated. By far, titania has played a much larger role in this scenario compared to other semiconductor photocatalysts due to its cost effectiveness, inert nature and photostability. Extensive literature analysis has shown many possibilities of improving the efficiency of photodecomposition over titania by combining the photoprocess with either physical or chemical operations. The resulting combined processes revealed a flexible line of action for wastewater treatment technologies. The choice of treatment method usually depends upon the composition of the wastewater. However, a lot more is needed from engineering design and modelling for successful application of the laboratory scale techniques to large-scale operation. The present review paper seeks to offer an overview of the dramatic trend in the use of the TiO2 photocatalyst for remediation and decontamination of wastewater, report the recent work done, important achievements and problems.

Particle length-dependent titanium dioxide nanomaterials’toxicity and bioactivity

Titanium dioxide (TiO2) nanomaterials have considerable beneficial applications varying from additives in paint, paper, plastics and cosmetics to uses in photocatalysts, solar cells and medical materials and devices. It has been established for many years that pigment-grade TiO2 (200 nm sphere) is relatively inert when internalized into a biological model system (in vivo or in vitro).

For this reason, TiO2 nanomaterials are an attractive alternative in applications where biological exposures will occur. Unfortunately, metal oxides on the nanoscale (one dimension <100 nm) may or may not exhibit the same toxic potential as the original material.

A further complicating issue is the effect of modifying or engineering of the nanomaterial to be structurally and geometrically different from the original material.

Results: TiO2 nanospheres, short (15 um) nanobelts were synthesized, characterized and tested for biological activity using primary murine alveolar macrophages and in vivo in mice. This study demonstrates that alteration of anatase TiO2 nanomaterial into a fibre structure of greater than 15 um creates a highly toxic particle and initiates an inflammatory response by alveolar macrophages.

These fibre-shaped nanomaterials induced inflammasome activation and release of inflammatory cytokines through a cathepsin B-mediated mechanism. Consequently, long TiO2 nanobelts interact with lung macrophages in a manner very similar to asbestos or silica.

Conclusions: These observations suggest that any modification of a nanomaterial, resulting in a wire, fibre, belt or tube, be tested for pathogenic potential.

As this study demonstrates, toxicity and pathogenic potential change dramatically as the shape of the material is altered into one that a phagocytic cell has difficulty processing resulting in lysosomal dysruptiion.

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Titanium dioxide nanoparticles induce oxidative stress and DNA adduct formation but not DNA breakage in human lung cells

Titanium dioxide (TiO2), also known as titanium (IV) oxide or anatase, is the naturally occurring oxide of titanium. It is also one of the most commercially used form.

To date, no parameter has been set for the average ambient air concentration of TiO2 nanoparticles (NP) by any regulatory agency. Previously conducted studies had established these nanoparticles to be mainly non-cyto- and -genotoxic, although they had been found to generate free radicals both acellularly (specially through photocatalytic activity) and intracellularly.

The present study determines the role ofTiO2-NP (anatase, <100 nm) using several parameters such as cyto- and genotoxicity, DNA-adduct formation and generation of free radicals following its uptake by human lung cells in vitro. For comparison, iron containing nanoparticles (hematite, Fe2O3, <100 nm) were used.

The results of this study showed that both types of NP were located in the cytosol near the nucleus. No particles were found inside the nucleus, in mitochondria or ribosomes.

Human lung fibroblasts (IMR-90) were more sensitive regarding cyto- and genotoxic effects caused by the NP than human bronchial epithelial cells (BEAS-2B). In contrast to hematite NP, TiO2-NP did not induce DNA-breakage measured by the Comet-assay in both cell types.

Generation of reactive oxygen species (ROS) was measured acellularly (without any photocatalytic activity) as well as intracellularly for both types of particles, however, the iron-containing NP needed special reducing conditions before pronounced radical generation. A high level of DNA adduct formation (8-OHdG) was observed in IMR-90 cells exposed to TiO2-NP, but not in cells exposed to hematite NP.

Our study demonstrates different modes of action for TiO2- and Fe2O3-NP. Whereas TiO2-NP were able to generate elevated amounts of free radicals, which induced indirect genotoxicity mainly by DNA-adduct formation, Fe2O3-NP were clastogenic (induction of DNA-breakage) and required reducing conditions for radical formation.

Author: Kunal BhattacharyaMaria DavorenJens BoertzRoel SchinsEik HoffmannElke Dopp
Credits/Source: Particle and Fibre Toxicology 2009, 6:17