Department of Occupational Health & Toxicology, School of Public Health, Shanghai Medical College of Fudan University, 130 Dongan Road, Shanghai 200032, China.
Department of Occupational & Environmental Health, School of Public Health, Xinxiang Medical University, 601 Jinsui Road, Xinxiang 453003, Henan Province, China.
Environ Int. 2020 Dec;145:106129. doi: 10.1016/j.envint.2020.106129. Epub 2020 Sep 17.
Excessive lead exposure is associated with adverse health effects. However, there is a lack of systematic investigation using large populations to ascertain acceptable exposure limits.
Our study was aimed to identify human exposure-response relationships between lead exposure and health-related outcomes, and to determine a benchmark dose (BMD).
A total of 1896 participants from a lead-acid battery plant were recruited. Blood lead levels (BLLs) were detected for all participants. Hematological parameters (n = 1896), micronuclei (MN) frequencies (n = 934), and relative telomere length (rTL) (n = 757) were also determined. Multivariate linear/Poisson regression analyses were performed to examine associations between BLLs and these health outcomes. Restricted cubic splines were used to identify dose-response relationships. Three BMD approaches were used to calculate BMD and its 95% lower confidence limit (BMDL).
Among all participants, BLLs show a right-skewed distribution (median, 185.40 μg/L; 25th - 75th percentile, 104.63-271.70 μg/L). There existed significant differences for red blood cell (RBC), hemoglobin (Hb), MN and rTL among different BLL dose groups. After adjusting for possible confounders, all indicators were significantly associated with BLLs. Restricted cubic splines show that there were linear dose-response relationships for RBC and Hb with BLLs, while non-linear for MN and rTL. Results from the three BMD approaches indicate that the dichotomous models were better than continuous models to calculate BMD and BMDL of BLLs. The conservative BMDL obtained from RBC data was 135 for total, 104 for male and 175 μg/L for female. The corresponding BMDL obtained from Hb data was 105 for total, 116 for male and 70 μg/L for female. As for MN data, the BMDL estimate was 66 for total, 69 for male and 64 μg/L for female. Finally, the BMDL from rTL data was 35 for total, 32 for male and 43 μg/L for female.
Our data show significant dose-response relationships between lead exposure and expressions of hematological toxicity and genotoxicity. The new BMDLs of 135 and 105 μg/L based on RBC and Hb, and even more strict level of 66 and 35 μg/L based on MN and rTL are lower than current exposure limits in China. Therefore, the four values can be considered as novel exposure limits. In addition, sex effect should be taken into account when setting occupational health standard. Considering that different biomarkers have different sensitivities, better understanding their relationships will certainly improve the current emphasis on precision health risk assessment.
过量的铅暴露与不良健康影响有关。然而，缺乏使用大量人群进行系统调查以确定可接受的暴露限值的研究。
本研究旨在确定铅暴露与健康相关结果之间的人体暴露-反应关系，并确定基准剂量（BMD）。
共招募了来自一家铅酸电池厂的 1896 名参与者。对所有参与者进行了血铅水平（BLL）检测。还测定了血液学参数（n=1896）、微核（MN）频率（n=934）和相对端粒长度（rTL）（n=757）。采用多元线性/泊松回归分析来检验 BLLs 与这些健康结果之间的关系。限制性立方样条用于确定剂量-反应关系。采用三种 BMD 方法计算 BMD 及其 95%置信下限（BMDL）。
在所有参与者中，BLL 呈右偏态分布（中位数，185.40μg/L；25%至 75%分位数，104.63-271.70μg/L）。不同 BLL 剂量组之间的红细胞（RBC）、血红蛋白（Hb）、MN 和 rTL 存在显著差异。在调整了可能的混杂因素后，所有指标均与 BLL 显著相关。限制性立方样条显示，RBC 和 Hb 与 BLLs 之间存在线性剂量反应关系，而 MN 和 rTL 则存在非线性关系。三种 BMD 方法的结果表明，二项模型比连续模型更适合计算 BLL 的 BMD 和 BMDL。从 RBC 数据中得出的保守 BMDL 总水平为 135μg/L，男性为 104μg/L，女性为 175μg/L。从 Hb 数据中得出的 BMDL 总水平为 105μg/L，男性为 116μg/L，女性为 70μg/L。对于 MN 数据，BMDL 估计值总水平为 66μg/L，男性为 69μg/L，女性为 64μg/L。最后，rTL 数据的 BMDL 为总水平 35μg/L，男性为 32μg/L，女性为 43μg/L。
我们的数据显示，铅暴露与血液毒性和遗传毒性的表达之间存在显著的剂量-反应关系。基于 RBC 和 Hb 的新 BMDL 值为 135 和 105μg/L，甚至基于 MN 和 rTL 的更严格水平为 66 和 35μg/L，均低于中国现行的暴露限值。因此，这四个值可以被视为新的暴露限值。此外，在制定职业健康标准时应考虑性别效应。考虑到不同的生物标志物具有不同的敏感性，更好地了解它们之间的关系肯定会提高当前对精准健康风险评估的重视。
