TDMATiO2

Titanium Dioxide Manufacturers Association(A sector group of)

Avenue E. Van Nieuwenhuyse, 4 box 1
B-1160 Brussels (Belgium)
Phone: +32 2 676 73 27

Titanium Dioxide Stewardship Council
2200 Pennsylvania Avenue, N.W.  Suite 100W Washington, D.C. 20037  (202) 557-3800 tel. (202) 557-3836 fax

Titanium Dioxide Product Safety Statement
on Inhalation Toxicology
Introduction
In February 2006 the International Agency for Research on Cancer (IARC) reclassified titanium
dioxide (TiO2). The final Monograph was published in January 2011. This document explains thesignificance of this reclassification and the position of TDMA.
Background/History
In 1989 IARC classified TiO2 as Group 3: („not classifiable for human carcinogenicity‟). TiO2 isusually used in toxicological studies as an inert comparator or control. However, three long term
studies were specifically carried out on TiO2, at exposure concentrations far above thoseexperienced in any workplace. After two years exposure at this „overload‟ concentration, lungtumors were found in rats.
The TiO2 industry commissioned a TiO2 inhalation study in mice, rats and hamsters and twoepidemiology studies in 15 TiO2 plants in Europe and North America.
Main findings of these studies
The epidemiology studies did not demonstrate an increased risk of lung cancer as a result ofoccupational exposure to TiO2.
The inhalation study clearly demonstrated that rats exhibited a different response to high TiO 2
dust concentrations compared with mice and hamsters.
The unique response developed by rats significantly adds to the evidence that the observed
effects are not relevant to humans. It was the dust overload that fundamentally caused theproblem in rats. There is no evidence that titanium dioxide itself has toxic properties that would
lead to cancer, nor that it presents a carcinogenic risk to humans at exposures experienced inthe workplace.
Actions in 2006
In February 2006 IARC carried out a review which resulted in the classification for TiO2 beingchanged from Group 3 to Group 2B, i.e. from: ‘not classifiable for human carcinogenicity’ to:‘possible human carcinogen’.
This reclassification was based entirely on the long term animal studies. The epidemiology
studies led the panel to conclude there was ‘insufficient evidence of carcinogenicity in humans’.
For the animal studies, the conclusion was: ‘sufficient evidence of carcinogenicity inexperimental animals’.

Explanation of IARC decision
The IARC rules state: there is “Sufficient evidence of carcinogenicity: …if… two or more
independent studies in one species carried out at different times or in different laboratories orunder different protocols” show evidence of tumours. The IARC expert group judged the threestudies on rats as qualifying.
Also, the new IARC rules require evidence of the „mechanism‟ of the tumour formation to betaken into account. This means that, if the tumour formation process in the rat took place in amanner that was not applicable to humans, then this should not be part of the overall
judgement.
The opinion of our experts is that the fact that the rat is uniquely sensitive should have kept TiO2
in category 3. However the IARC Expert Panel did not agree.
Conclusions on IARC
IARC assesses the potential hazard, not the risk. The epidemiology studies did not show anincrease in lung cancer in the TiO2 workforce as a result of exposure to TiO2 dust.
We believe it is important that everyone should be fully informed on this issue, because there
will inevitably be concern and possible misinterpretation of the term ‘possible humancarcinogen’. Our M/SDS‟s have been updated accordingly.
Irrespective of the IARC ruling, TDMA members place paramount importance on the health andsafety of their employees and the community at large, and strongly believe that it is always
prudent to take all possible precautions against all potential work place exposures (noise, dust,chemicals etc.). We therefore support the continuous improvement of procedures andprocesses to minimize any potential exposure.

2