Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
Arch Toxicol. 2022 Apr;96(4):969-985. doi: 10.1007/s00204-022-03247-9. Epub 2022 Feb 21.
Translating particle dose from in vitro systems to relevant human exposure remains a major challenge for the use of in vitro studies in assessing occupational hazard and risk of particle exposure. This study aimed to model the lung deposition and retention of welding fume particles following occupational scenarios and subsequently compare the lung doses to those used in vitro. We reviewed published welding fume concentrations and size distributions to identify input values simulating real-life exposure scenarios in the multiple path particle dosimetry (MPPD) model. The majority of the particles were reported to be below 0.1 μm and mass concentrations ranged between 0.05 and 45 mg/m. Following 6-h exposure to 5 mg/m with a count median diameter of 50 nm, the tracheobronchial lung dose (0.89 µg/cm) was found to exceed the in vitro cytotoxic cell dose (0.125 µg/cm) previously assessed by us in human bronchial epithelial cells (HBEC-3kt). However, the tracheobronchial retention decreased rapidly when no exposure occurred, in contrast to the alveolar retention which builds-up over time and exceeded the in vitro cytotoxic cell dose after 1.5 working week. After 1 year, the tracheobronchial and alveolar retention was estimated to be 1.15 and 2.85 µg/cm, respectively. Exposure to low-end aerosol concentrations resulted in alveolar retention comparable to cytotoxic in vitro dose in HBEC-3kt after 15-20 years of welding. This study demonstrates the potential of combining real-life exposure data with particle deposition modelling to improve the understanding of in vitro concentrations in the context of human occupational exposure.
将体外系统中的颗粒剂量转化为相关的人体暴露仍然是利用体外研究评估职业危害和颗粒暴露风险的主要挑战。本研究旨在模拟职业情景下焊接烟尘颗粒的肺部沉积和保留,并随后将肺部剂量与体外使用的剂量进行比较。我们查阅了已发表的焊接烟尘浓度和粒径分布数据,以确定用于多路径颗粒剂量学(MPPD)模型模拟真实暴露情景的输入值。研究报告称,大多数颗粒的粒径都小于 0.1μm,质量浓度在 0.05 至 45mg/m 之间。暴露于 5mg/m 的烟尘中 6 小时后,发现计数中值粒径为 50nm 的情况下,气管支气管肺剂量(0.89µg/cm)超过了我们之前在人支气管上皮细胞(HBEC-3kt)中评估的体外细胞毒性剂量(0.125µg/cm)。然而,与肺泡保留不同的是,当没有暴露发生时,气管支气管保留迅速下降,肺泡保留会随着时间的推移而逐渐增加,并在 1.5 个工作周后超过体外细胞毒性剂量。1 年后,气管支气管和肺泡的保留量估计分别为 1.15µg/cm 和 2.85µg/cm。暴露于低浓度气溶胶中,15-20 年后,HBEC-3kt 的肺泡保留量与体外细胞毒性剂量相当。本研究表明,将真实暴露数据与颗粒沉积模型相结合,有助于提高对人体职业暴露中体外浓度的理解。