Lung cancer mortality in the French cohort of titanium dioxide workers: some aetiological insights.

Titanium dioxide (TiO <sub>2</sub> ) is widely used in construction, food, cosmetic and medical industry. The current evidence on TiO <sub>2</sub> carcinogenicity in humans is considered inadequate. As French participants of the European cohort of TiO <sub>2</sub> workers exhibited an increase in mortality from lung cancer, we aimed at investigating whether TiO <sub>2</sub> exposure, co-exposures or smoking can explain this increase. We reanalysed the data of 833 French male workers (follow-up period 1968-1997) and used multiple imputation to complete their smoking status. We considered respirable TiO <sub>2</sub> dust as primary exposure of interest, estimated as continuous cumulative (mg/m <sup>3</sup> -year) and annual average (mg/m <sup>3</sup> ) concentrations and binary and 4-class categorical variables, with cut-off values of 0.3 and 2.4 mg/m <sup>3</sup> (the German and American occupational exposure limits, respectively). For each exposure metric, we estimated HRs and associated 95% CIs, using Cox regression models adjusted for calendar period, exposure duration and smoking. The fully adjusted model yielded a HR=3.7 (95% CI=0.79 to 17.95) for TiO <sub>2</sub> -exposed workers vs unexposed and a HR=27.33 (95% CI=4.35 to 171.84) for those exposed to >2.4 mg/m <sup>3</sup> as annual average concentration. Employment duration was negatively related with lung cancer mortality, therefore cumulative exposure had a small effect on mortality (HR=1.03 (95% CI=0.99 to 1.08) per mg/m <sup>3</sup> -year). This study suggests a positive relationship between TiO <sub>2</sub> exposure and lung cancer mortality in TiO <sub>2</sub> workers, whatever the exposure variable used, despite a limited statistical power in some models. The results question the current evidence on TiO <sub>2</sub> carcinogenicity in humans but need to be confirmed in other cohorts, using different statistical approaches