• Can titanium dioxide cause cancer?

Robust, scientific evidence shows that titanium dioxide is safe. Here’s what you need to know.

Titanium dioxide is a bright white pigment used across many different industries due to its unique and useful qualities. It is mostly used in everyday products such as paints, plastics, paper and inks.

Current scientific evidence shows it is safe to use products containing titanium dioxide:

• Decades of industry and independent research has found no evidence of potential cancer risk to humans from titanium dioxide.
• Studies that have linked titanium dioxide to cancer risk are based on an excessive lung overload effect observed in rats, involving exposure to very high quantities of titanium dioxide by inhalation.  The extreme doses used in scientific studies with rats  do not reflect normal conditions of use or exposure, and there is no evidence of potential cancer risk to workers who may be exposed to TiO₂ on a daily basis.

Introduction

Titanium dioxide is a well-established and omnipresent natural substance. Titanium dioxide – also known by its chemical name TiO₂ – has been assessed for safety by a large number of regulatory authorities and has consistently been found to be safe for a broad variety of all applications.

There have been recent discussions about whether it may be harmful to humans or even cause cancer. Here are the main questions and the key facts.

Titanium dioxide has been classified as a category 2 carcinogen by inhalation by the EU. What does this mean?

In 2020, the EU classified titanium dioxide in its powder form as a suspected carcinogen by inhalation under the EU’s Classification and Labelling (CLP) Regulation.

There is no scientific evidence of cancer in humans from exposure to titanium dioxide. The classification is based on one rat inhalation study which was conducted in excessive overload conditions. The TDMA believe this study is not an acceptable scientific basis for the classification and a thorough weight of evidence assessment confirms that TiO₂ does not induce cancer and does not have an intrinsic property to cause cancer.

The EU authorities have underlined in the classification that the suspected hazard could occur if dust is inhaled in extremely high concentrations over a long period of time.

So, why did the EU classify titanium dioxide? And what does the classification mean for consumers? Here is what you need to know.

Why did IARC assess titanium dioxide as “possibly carcinogenic” by inhalation?

In 2006, the International Agency for Research on Cancer (IARC) concluded that there was inadequate evidence to state that titanium dioxide causes cancer in humans.

IARC did conclude, however, that titanium dioxide is “possibly carcinogenic to humans by means of inhalation” (category 2b). It found inadequate evidence in humans but sufficient evidence of cancer risk in animals.

The IARC assessment is based on three rat studies carried out more than 20 years ago, under conditions that are not aligned with the EU’s current testing guidelines.

Furthermore, it is generally recognised that rats are uniquely sensitive to the effects of “lung overload”, a condition that is not observed in humans.

IARC’s findings did not trigger any other regulatory action in Europe.

Why did the EU classify titanium dioxide as a possible carcinogen by inhalation more than 10 years later?

After a proposal by the French Authorities in 2016, the Committee for Risk Assessment (RAC) of the European Chemicals Agency (ECHA) concluded in June 2017 that TiO₂ met the criteria to be classified as a substance suspected of causing cancer (category 2) if inhaled.

The opinion of the RAC is clear in stating that there are no robust carcinogenicity studies in species other than rats, and that the relevance of this data for humans is unclear. Moreover, the RAC’s opinion does not consider data for more than 24,000 workers, that demonstrates there is no link between cancer in humans and exposure to titanium dioxide.

The RAC found that the suspected hazard described for TiO₂ is not specific to the substance but common to all dusts/powders known as ‘poorly soluble low-toxicity substances’.

The suspected hazard is linked to the form of these particles which when inhaled in a very high concentration over a long period of time can overwhelm the lungs in a rat, the so-called ‘lung overload’ condition. This might result in the carcinogenic effect which has been observed in rats, but not other species or in humans.

The EU’s decision to classify titanium dioxide as a possible carcinogen by inhalation is not based on any new scientific evidence, but rather reflects an extra precautionary approach to the well-known hazard of breathing too much dust.

Are there any risks for consumers?

The RAC underlined that it does not “take into account the likelihood of exposure to the substance and therefore does not address the risks of exposure.”In other words, the opinion of the RAC does not concern whether the hazard described will ever occur in the real world.

However, studies on the toxicology of substances should also consider the principle of dosage, often referred to by the phrase: ‘The dose makes the poison.’ All chemicals – even water and oxygen – can be toxic to humans if consumed at high or extremely high doses.

Many animal studies on substances test the effects of a substance at high doses, which are not found in real-world situations. This is the case for titanium dioxide. If the extreme inhalation conditions specified in the classification are removed, titanium dioxide is not harmful. The specific effects on animals may also not be replicated in humans, as in the case of the ‘lung overload’ observed in rats.

This was reaffirmed at a meeting between the European Commission, Member States and interested parties. It was concluded that there are “negligible” concerns for consumers given the extremely high level of exposure of inhalable titanium dioxide particles required for the substance to be harmful in any way. Such conditions were considered unrealistic by the authorities under normal and foreseeable circumstances.

What does the classification of titanium dioxide mean for consumers?

The classification adopted by the European Commission is clear that the suspected hazard is limited to TiO₂ powders, if inhaled over a very long period at very high concentrations.

This means that the classification is of very limited relevance to consumers. In most products, TiO₂ is incorporated in the finished product and there is almost no risk of inhaling it. Likewise, the TiO₂ in finished products such as paints and plastics is either insoluble or solid and cannot be inhaled.

Yet, the classification means that some products may need to carry labels or statements warning about dust even if it is unrealistic that consumers will be exposed to the hazard at all, let alone to a harmful level. In other products, like cosmetics and toys, there may be reassessment to reaffirm the safety of TiO₂.

In summary:

1. The EU classification is not based on new information or hazard;
2. The suspected hazard will not occur in real-world conditions under realistic circumstances;
3. The safety of titanium dioxide for humans remains underpinned by decades of data.

2/ Is titanium dioxide safe to eat?

Yes – E171, the food grade of titanium dioxide, has gone through rigorous European testing and classification, which proved that titanium dioxide has not been found to persist or accumulate in the human body.

Numerous studies have consistently confirmed the safety of E171.

What researchers and authorities have said about E171’s safety

In 2015, a group of researchers from the Food and Environment Research Agency in the UK, the Food Institute at the Tübitak Marmara Research Center in Turkey and the RIKILT Institute of Food Safety in the Netherlands carried out a study into the oral consumption of nano and larger particles of titanium dioxide.

Their research found that there would be no “significant internal exposure of the consumer to the nanoparticles”.

In 2016, while reviewing food additives that had been approved prior to 2009, the European Food Safety Authority (EFSA) reviewed the latest information about E171. It found that the data on E171 showed no health concerns for consumers. The safety of E171 is not influenced by the particle size because it is not absorbed into the human body.

Why did France decide to suspend the use of E171?

The French decision is mostly based on a study in 2017 by the National Agronomic Research Institute (INRA). However, the findings of this study cannot be extrapolated to humans and were not corroborated by other similar research.

In 2017, a study was published by the French National Agronomic Institute (INRA), claiming risks of cancer from ingestion of titanium dioxide observed in rats. However, much like inhalation studies, the protocol used in this research cannot be extrapolated to conclude that it could cause cancer in humans.

In fact, INRA itself clearly states that its findings cannot be extended to draw conclusions for human health, and that they do not comply with OECD guidelines for the testing of chemicals. Other studies carried out in conformity with OECD guidelines have not shown any adverse effect at doses considerably higher than those used in the INRA study.

EFSA itself was asked to review the findings of the INRA study in 2018 and concluded that the results of the INRA study do not warrant a revision of the safety approval of E171. In 2019, the Michigan State University and University of Nebraska Medical Center looked into concerns raised by the INRA study. While using higher doses than INRA, they did not observe any statistically significant changes associated with ingestion of E171 in any immune parameters or cancer in the gastrointestinal tract.

The former European Commissioner for Health & Food Safety, Vytenis Andriukaitis, reiterated this on 20 February 2019 and underlined that the use of titanium dioxide as an additive is not of safety concern. The Commissioner also reasserted EFSA’s conclusion that the oral absorption of TiO₂ is extremely low and independent of particle size.

In summary:

1. The French suspension of E171 is not based on new information;
2. The European Food Safety Authority has consistently confirmed the safety of E171