Lung cancer risk assessment associated with exposure to hexavalent chromium: Results of pooled analysis of three cohorts

Quantitative risk assessments of inhaled hexavalent chromium (CrVI) have primarily relied on studies of two chromate production worker cohorts, involving male workers exposed to high concentrations of airborne CrVI that caused an exposure-dependent increase in lung cancer and elicited severe respiratory irritation. An additional larger cohort of CrVI-exposed aerospace workers, including women, and with lower intensity exposures, was recently updated with a longer follow-up period and reconstructed cumulative exposure estimates. A risk assessment was conducted using a pooled analysis of individual-level dose-response information from three cohorts, including the aerospace workers, to generate lung cancer inhalation unit risk estimates (IURs). IURs are estimates of the upper-bound of lifetime increased cancer risk from continuous inhalation exposure to 1 µg/m3 and are commonly used in quantitative risk assessment. Use of the pooled cohort broadens the range for dose-response analysis due to the comparatively low exposures to CrVI in the aerospace cohort; moreover, sex-specific risks could be expanded with the inclusion of female workers. Standardized logistic regression using person-year-specific weighted cumulative exposures was used to estimate the probability of lung cancer mortality, with varied weighting approaches. The primary model included male workers from all cohorts with a minimum of one year of CrVI exposure; secondary analyses examined the impacts of sex and short-term exposure. The best fit dose-response function was a Michaelis-Menten relationship. The IUR from the primary model was 0.01 (95%CI: 0.006–0.01) per µg/m3. Best estimates of the three IURs from secondary analyses, which removed the respiratory use adjustment factors, included females from the aerospace cohort and added workers with less than one year of exposure from the chromate production cohorts, were relatively consistent with the primary analyses, ranging from 0.008 to 0.03 per µg/m3. Use of this pooled IUR estimate allows for inclusion of a broader dose-response range and reduced uncertainty through use of a larger population, additional years of follow-up, and incorporation of broader geographical and cohort characteristics with improved relevancy to the general population.

吸入性六价铬（hexavalent chromium, CrVI）的定量风险评估，此前主要依托两项铬酸盐生产工人队列研究开展：研究对象为暴露于高浓度空气传播六价铬的男性工人，该暴露水平可引发暴露剂量依赖性的肺癌风险升高，并诱发严重呼吸道刺激症状。另有一项规模更大的六价铬暴露航空航天工人队列（涵盖女性工人，暴露强度较低），近期已完成更新，延长了随访时长并重构了累积暴露评估结果。研究团队针对包括该航空航天队列在内的三项队列的个体水平剂量-反应信息展开合并分析，以此开展风险评估，进而推导肺癌吸入单位风险估计值（inhalation unit risk estimates, IURs）。吸入单位风险估计值（IURs）指的是：持续吸入浓度为1 µg/m³的污染物时，个体终生罹患癌症的超额风险上限值，该指标广泛应用于定量风险评估工作中。由于该航空航天队列的六价铬暴露水平相对较低，纳入该队列后可拓宽剂量-反应分析的覆盖范围；此外，纳入女性工人后，还可进一步细化性别特异性的风险分析。研究采用多种加权方法，基于人年特异性加权累积暴露量开展标准化logistic回归（logistic regression）分析，以估算肺癌死亡的发生概率。核心模型纳入了所有队列中至少有1年六价铬暴露史的男性工人；辅助分析则分别考察了性别与短期暴露对风险的影响。拟合效果最优的剂量-反应函数为米氏动力学（Michaelis-Menten）关系。核心模型得到的吸入单位风险估计值为0.01（95%置信区间：0.006~0.01）每1 µg/m³。在移除呼吸道使用调整因子后的三项辅助分析中，纳入航空航天队列女性工人、并补充铬酸盐生产队列中暴露时长不足1年的工人后得到的最优估计值，与核心分析结果相对一致，范围介于0.008~0.03每1 µg/m³之间。采用该合并得到的吸入单位风险估计值，可通过以下方式拓宽剂量-反应分析覆盖范围并降低不确定性：纳入更大规模的研究人群、延长随访时长，同时纳入覆盖更广地理区域与队列特征的样本，提升了研究结果与普通人群的相关性。