Titanium Dioxide (TiO2) exposure among workers in German manufacturing plants: research on lung cancer Mortality (TiMo)

Status:

completed 02/2026

Aims:

Re-analysis
Re-analysis of a retrospective cohort study among German factory workers to assess the association between lung cancer mortality and titanium dioxide (TiO₂), taking into account data on smoking status (observation period 1950-1999).

Feasibility
Assessing Feasibility Assessing the feasibility of a mortality follow-up for the study cohort via record linkage with the responsible cancer registries of Lower Saxony and North-Rhine Westphalia to update the study dataset with new information regarding vital status from the year 2000 and onward.

Activities/Methods:

Re-analysis
The study investigates a historic worker cohort (N=7,410) from three German TiO₂ factories between 1950 and 1999. Lung cancer mortality in the cohort was compared with that in the general population (external mortality comparison). To this end, standardized mortality ratios (SMRs) were calculated, stratified by exposure level, and indirectly adjusted for smoking. Furthermore, the association between the amount of TiO₂ exposure and lung cancer mortality was examined within the cohort (internal mortality comparison). For this purpose, the hazard ratio (HR) for death from lung cancer was modeled using Cox regressions with exposure lagged by 0/10/20 years, adjusted for five occupational co-exposures, and stratified by smoking status.

Feasibility
The feasibility assessment required detailed coordination with the relevant state cancer registries regarding specific procedures, the development of a data protection plan, and the approval of the relevant ethics committee. The three German TiO₂ factories had to be informed about the entire project (re-analysis and feasibility assessment).

Results:

Re-analysis
A total of n=4,862 men met all inclusion criteria. Women (n=347) were excluded from the analyses due to the small sample size. Smoking data were available for 55% of the male cohort. During the observation period (1950¬1999), 67% more workers died of lung cancer than would have been expected based on their age structure; no trend across exposure terciles was apparent. In addition, a weak association was found between the level of cumulative TiO₂ exposure and lung cancer mortality among never-smokers (for exposure lagged by 20 years), but not among ever-smokers. Applying the HR calculated for never-smokers to median exposure values in the cohort yields a 47% increased hazard of dying from lung cancer.

Feasibility
Both cancer registries generally supported a record linkage between the cohort's encrypted person data (name, address, date of birth) and their own encrypted database. A detailed plan for the actual realization of the record linkage, along with the necessary data protection provisions, was developed and approved by the registries' relevant expert committees and data protection officials. A positive vote was obtained from the Ethics Committee of the Rhineland-Palatinate Medical Association. Representatives of the TiO₂ factories requested to be informed about new findings. The record linkage is scheduled to be carried out in 2026. This will provide the basis for an analysis of the cohort using updated mortality data.

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