Lung cancer mortality of workers occupationally exposed to titanium dioxide in Germany: new insights from a retrospective cohort study after accounting for smoking status.

Evidence regarding carcinogenic effects of inhaled titanium dioxide (TiO2) dust is inconclusive. Several cohort studies investigated worker populations in TiO2 factories, the largest of which included 15,017 individuals in multiple European countries. We have re-analyzed the data of the German sub-cohort from this European study to investigate the association between TiO2 exposure and lung cancer mortality. The observation period covered 50 years (1950-1999). Standardized mortality ratios (SMR) were calculated and indirectly adjusted for smoking. Cox regression analysis was used to estimate hazard ratios (HR), stratified by smoking status, adjusted for co-exposures, and lagged by 0/10/20 years. Cumulative exposure was estimated through a job-exposure matrix. 4862 male workers from three TiO2 factories were included (131,475 person-years). Smoking status was available for 55% of workers. At the end of follow-up, 1015 deaths were recorded, 115 of which due to lung cancer. The adjusted SMR for lung cancer mortality was 1.67 (n = 4650; 95%CI: 1.41-1.98), with no trend across exposure levels. Adjusted Cox models showed no increased hazard for ever-smokers and workers with unknown smoking status, and a weak association for never-smokers (n = 2880; HR = 1.07; 95%CI: 0.96-1.21), with exposure lagged by 20 years. This is one of the few occupational cohort studies on TiO2 inhalation where smoking was accounted for in analyses. Exposure-response associations of similar magnitude for TiO2 dust and lung cancer mortality have been reported by other studies. However, findings need to be interpreted with caution due to several methodological limitations, highlighting the need for further research with new data.