Department of Occupational and Environmental Health, Center for Primary Care and Public Health (Unisanté), University of Lausanne, Epalinges-Lausanne, Switzerland
Department of Occupational and Environmental Health, Center for Primary Care and Public Health (Unisanté), University of Lausanne, Epalinges-Lausanne, Switzerland.
Occup Environ Med. 2020 Nov;77(11):795-797. doi: 10.1136/oemed-2020-106522. Epub 2020 Jul 31.
Titanium dioxide (TiO) is widely used in construction, food, cosmetic and medical industry. The current evidence on TiO carcinogenicity in humans is considered inadequate. As French participants of the European cohort of TiO workers exhibited an increase in mortality from lung cancer, we aimed at investigating whether TiO 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 dust as primary exposure of interest, estimated as continuous cumulative (mg/m-year) and annual average (mg/m) concentrations and binary and 4-class categorical variables, with cut-off values of 0.3 and 2.4 mg/m (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-exposed workers vs unexposed and a HR=27.33 (95% CI=4.35 to 171.84) for those exposed to >2.4 mg/m 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-year).
This study suggests a positive relationship between TiO exposure and lung cancer mortality in TiO workers, whatever the exposure variable used, despite a limited statistical power in some models. The results question the current evidence on TiO carcinogenicity in humans but need to be confirmed in other cohorts, using different statistical approaches.
二氧化钛（TiO）广泛应用于建筑、食品、化妆品和医疗行业。目前关于 TiO 对人类致癌性的证据被认为不足。由于法国 TiO 工人队列的研究结果显示，其肺癌死亡率有所增加，我们旨在研究 TiO 暴露、共暴露或吸烟是否可以解释这种增加。
我们重新分析了 833 名法国男性工人（随访期为 1968 年至 1997 年）的数据，并使用多重插补法完成了他们的吸烟状况。我们将可吸入 TiO 粉尘作为主要关注的暴露因素，将其估计为连续累积（mg/m-年）和年度平均（mg/m）浓度以及二进制和 4 类分类变量，其截断值分别为 0.3 和 2.4mg/m（德国和美国职业暴露限值）。对于每种暴露指标，我们使用 Cox 回归模型调整了日历期间、暴露持续时间和吸烟情况，估计了 HR 和相关的 95%置信区间。
在完全调整后的模型中，暴露于 TiO 的工人与未暴露的工人相比，HR 为 3.7（95%CI=0.79 至 17.95），而暴露于 TiO 的工人中，暴露于 2.4mg/m 作为年度平均浓度的工人 HR 为 27.33（95%CI=4.35 至 171.84）。就业时间与肺癌死亡率呈负相关，因此累积暴露对死亡率的影响较小（HR=1.03（95%CI=0.99 至 1.08）/mg/m-年）。
这项研究表明，无论使用何种暴露变量，TiO 暴露与 TiO 工人的肺癌死亡率之间存在正相关关系，尽管在某些模型中统计效力有限。结果对目前关于 TiO 对人类致癌性的证据提出了质疑，但需要在其他队列中使用不同的统计方法加以证实。
