Hopf Nancy B, Bourgkard Eve, Demange Valérie, Hulo Sébastien, Sauvain Jean-Jacques, Levilly Ronan, Jeandel Fanny, Robert Alain, Guichard Yves, Pralong Jacques André, Chérot-Kornobis Nathalie, Edmé Jean-Louis, Wild Pascal
Department of Occupational and Environmental Health, Center for Primary Care and Public Health (Unisanté), University Lausanne, Lausanne, Switzerland.
Department of Epidemiology, National Research and Safety Institute (INRS), Vandoeuvre cedex, France.
JMIR Res Protoc. 2019 Aug 2;8(8):e13744. doi: 10.2196/13744.
Exposure to aerosols from metalworking fluids (MWF) has previously been related to a series of adverse health outcomes (eg, cancer, respiratory diseases). Our present epidemiological study focuses on occupational exposures to MWF and a panel of exposure and effect biomarkers. We hypothesize that these health outcomes are caused by particle exposure that generates oxidative stress, leading to airway inflammation and ultimately to chronic respiratory diseases. We aimed to assess whether MWF exposure, in particular as characterized by its oxidative potential, is associated with biomarkers of oxidative stress and inflammation as well as genotoxic effects.
The ultimate goal is to develop exposure reduction strategies based on exposure determinants that best predict MWF-related health outcomes. The following relationships will be explored: (1) exposure determinants and measured exposure; (2) occupational exposure and preclinical and clinical effect markers; (3) exposure biomarkers and biomarkers of effect in both exhaled breath condensate and urine; and (4) biomarkers of effect, genotoxic effects and respiratory symptoms.
At least 90 workers from France and Switzerland (30 controls, 30 exposed to straight MWF and 30 to aqueous MWF) were followed over three consecutive days after a nonexposed period of at least two days. The exposure assessment is based on MWF, metal, aldehyde, and ultrafine particle number concentrations, as well as the intrinsic oxidative potential of aerosols. Furthermore, exposure biomarkers such as metals, metabolites of polycyclic aromatic hydrocarbons and nitrosamine are measured in exhaled breath condensate and urine. Oxidative stress biomarkers (malondialdehyde, 8-isoprostane, 8-hydroxy-2'-deoxyguanosine, nitrates, and nitrites) and exhaled nitric oxide, an airway inflammation marker, are repeatedly measured in exhaled breath condensate and urine. Genotoxic effects are assessed using the buccal micronucleus cytome assay. The statistical analyses will include modelling exposure as a function of exposure determinants, modelling the evolution of the biomarkers of exposure and effect as a function of the measured exposure, and modelling respiratory symptoms and genotoxic effects as a function of the assessed long-term exposure.
Data collection, which occurred from January 2018 until June 2019, included 20 companies. At the date of writing, the study included 100 subjects and 29 nonoccupationally exposed controls.
This study is unique as it comprises human biological samples, questionnaires, and MWF exposure measurement. The biomarkers collected in our study are all noninvasive and are useful in monitoring MWF exposed workers. The aim is to develop preventative strategies based on exposure determinants related to health outcomes.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13744.
此前，接触金属加工液（MWF）产生的气溶胶与一系列不良健康后果（如癌症、呼吸系统疾病）有关。我们目前的流行病学研究聚焦于MWF的职业暴露以及一组暴露和效应生物标志物。我们假设这些健康后果是由产生氧化应激的颗粒物暴露引起的，进而导致气道炎症并最终引发慢性呼吸系统疾病。我们旨在评估MWF暴露，尤其是以其氧化潜能为特征的暴露，是否与氧化应激、炎症生物标志物以及遗传毒性效应相关。
最终目标是基于能最佳预测MWF相关健康后果的暴露决定因素制定减少暴露的策略。将探索以下关系：（1）暴露决定因素与实测暴露；（2）职业暴露与临床前和临床效应标志物；（3）呼出气冷凝物和尿液中的暴露生物标志物与效应生物标志物；（4）效应生物标志物、遗传毒性效应和呼吸道症状。
来自法国和瑞士的至少90名工人（30名对照组、30名暴露于纯MWF组和30名暴露于含水MWF组）在至少两天的非暴露期后连续三天接受随访。暴露评估基于MWF、金属、醛和超细颗粒物数量浓度，以及气溶胶的固有氧化潜能。此外还在呼出气冷凝物和尿液中测量金属、多环芳烃和亚硝胺的代谢物等暴露生物标志物。在呼出气冷凝物和尿液中反复测量氧化应激生物标志物（丙二醛、8-异前列腺素、8-羟基-2'-脱氧鸟苷、硝酸盐和亚硝酸盐）以及气道炎症标志物呼出气一氧化氮。使用颊黏膜微核细胞分析法评估遗传毒性效应。统计分析将包括将暴露建模为暴露决定因素的函数，将暴露和效应生物标志物的演变建模为实测暴露的函数，以及将呼吸道症状和遗传毒性效应建模为评估的长期暴露的函数。
2018年1月至2019年6月的数据收集涵盖了20家公司。在撰写本文时，该研究包括100名受试者和29名非职业暴露对照组。
本研究独一无二，因为它包含人类生物样本、问卷调查和MWF暴露测量。我们研究中收集的生物标志物均为非侵入性，对监测MWF暴露工人很有用。目的是基于与健康后果相关的暴露决定因素制定预防策略。
国际注册报告标识符（IRRID）：DERR1-10.2196/13744。
