Objectives Titanium dioxide (TiO2) is widely used in construction, food, cosmetic and medical industry. The current evidence on TiO2 carcinogenicity in humans is considered inadequate. As French participants of the European cohort of TiO2 workers exhibited an increase in mortality from lung cancer, we aimed at investigating whether TiO2 exposure, co-exposures or smoking can explain this increase.
Methods 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 TiO2 dust as primary exposure of interest, estimated as continuous cumulative (mg/m3-year) and annual average (mg/m3) concentrations and binary and 4-class categorical variables, with cut-off values of 0.3 and 2.4 mg/m3 (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.
Results The fully adjusted model yielded a HR=3.7 (95% CI=0.79 to 17.95) for TiO2-exposed workers vs unexposed and a HR=27.33 (95% CI=4.35 to 171.84) for those exposed to >2.4 mg/m3 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/m3-year).
Conclusion This study suggests a positive relationship between TiO2 exposure and lung cancer mortality in TiO2 workers, whatever the exposure variable used, despite a limited statistical power in some models. The results question the current evidence on TiO2 carcinogenicity in humans but need to be confirmed in other cohorts, using different statistical approaches.
- mortality studies
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Contributors IGC designed and conducted this study and drafted the manuscript, AG-G and PW conducted statistical analyses; KS and DL provided access to the data. All authors discussed the study methodology, read the manuscript, critically reviewed it and agreed on the final version.
Funding This work was supported by the University of Lausanne.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The use of the individual data was approved by the French Data Protection Authority (CNIL), Authorisation No 999250.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data may be obtained from a third party and are not publicly available.
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