RT Journal Article
SR Electronic
T1 Lung cancer mortality in the European cohort of titanium dioxide workers: a reanalysis of the exposure–response relationship
JF Occupational and Environmental Medicine
JO Occup Environ Med
FD BMJ Publishing Group Ltd
SP oemed-2021-108030
DO 10.1136/oemed-2021-108030
A1 Guseva Canu, Irina
A1 Gaillen-Guedy, Alan
A1 Antilla, Ahti
A1 Charles, Sandrine
A1 Fraize-Frontier, Sandrine
A1 Luce, Danièle
A1 McElvenny, Damien Martin
A1 Merletti, Franco
A1 Michel, Cecile
A1 Pukkala, Eero
A1 Schubauer-Berigan, Mary K
A1 Straif, Kurt
A1 Wild, Pascal
A1 Richardson, David B
YR 2022
UL http://oem.bmj.com/content/early/2022/05/02/oemed-2021-108030.abstract
AB Objectives Animal bioassays have demonstrated convincing evidence of the potential carcinogenicity to humans of titanium dioxide (TiO2), but limitations in cohort studies have been identified, among which is the healthy worker survivor effect (HWSE). We aimed to address this bias in a pooled study of four cohorts of TiO2 workers.Methods We reanalysed data on respirable TiO2 dust exposure and lung cancer mortality among 7341 male workers employed in TiO2 production in Finland, France, UK and Italy using the parametric g-formula, considering three hypothetical interventions: setting annual exposures at 2.4 (U.S. occupational exposure limit), 0.3 (German limit) and 0 mg/m3 for 25 and 35 years.Results The HWSE was evidenced. Taking this into account, we observed a positive association between lagged cumulative exposure to TiO2 and lung cancer mortality. The estimated number of lung cancer deaths at each age group decreased across increasingly stringent intervention levels. At age 70 years, the estimated number of lung cancer deaths expected in the cohort after 35-year exposure was 293 for exposure set at 2.4 mg/m3, 235 for exposure set at 0.3 mg/m3, and 211 for exposure set at 0 mg/m3.Conclusion This analysis shows that HWSE can hide an exposure–response relationship. It also shows that TiO2 epidemiological data could demonstrate an exposure–effects relationship if analysed appropriately. More epidemiological studies and similar reanalyses of existing cohort studies are warranted to corroborate the human carcinogenicity of TiO2. This human evidence, when combined with the animal evidence, strengthens the overall evidence of carcinogenicity of TiO2.Data sharing not applicable as no datasets generated and/or analysed for this study. Not applicable.