Department of Environmental Sciences, Informatics and Statistics, University Ca' Foscari of Venice, via Torino 155, 30170 Venice Mestre, Italy.
Department of Environmental Sciences, Informatics and Statistics, University Ca' Foscari of Venice, via Torino 155, 30170 Venice Mestre, Italy; GreenDecision S.r.l., 30170 Venice Mestre, Italy.
NanoImpact. 2022 Jan;25:100373. doi: 10.1016/j.impact.2021.100373. Epub 2021 Dec 10.
The assessment of the safety of nano-biomedical products for patients is an essential prerequisite for their market authorization. However, it is also required to ensure the safety of the workers who may be unintentionally exposed to the nano-biomaterials (NBMs) in these medical applications during their synthesis, formulation into products and end-of-life processing and also of the medical professionals (e.g., nurses, doctors, dentists) using the products for treating patients. There is only a handful of workplace risk assessments focussing on NBMs used in medical applications. Our goal is to contribute to increasing the knowledge in this area by assessing the occupational risks of magnetite (FeO) nanoparticles coated with PLGA-b-PEG-COOH used as contrast agent in magnetic resonance imaging (MRI) by applying the software-based Decision Support System (DSS) which was developed in the EU H2020 project BIORIMA. The occupational risk assessment was performed according to regulatory requirements and using state-of-the-art models for hazard and exposure assessment, which are part of the DSS. Exposure scenarios for each life cycle stage were developed using data from literature, inputs from partnering industries and results of a questionnaire distributed to healthcare professionals, i.e., physicians, nurses, technicians working with contrast agents for MRI. Exposure concentrations were obtained either from predictive exposure models or monitoring campaigns designed specifically for this study. Derived No-Effect Levels (DNELs) were calculated by means of the APROBA tool starting from in vivo hazard data from literature. The exposure estimates/measurements and the DNELs were used to perform probabilistic risk characterisation for the formulated exposure scenarios, including uncertainty analysis. The obtained results revealed negligible risks for workers along the life cycle of magnetite NBMs used as contrast agent for the diagnosis of tumour cells in all exposure scenarios except in one when risk is considered acceptable after the adoption of specific risk management measures. The study also demonstrated the added value of using the BIORIMA DSS for quantification and communication of occupational risks of nano-biomedical applications and the associated uncertainties.
评估纳米生物医学产品对患者的安全性是其获得市场授权的必要前提。然而，还需要确保在这些医疗应用中合成、配制成产品以及处理产品生命周期结束时，可能无意中接触纳米生物材料（NBM）的工人，以及使用这些产品治疗患者的医疗专业人员（例如护士、医生、牙医）的安全。目前只有少数针对医疗应用中使用的 NBM 的工作场所风险评估。我们的目标是通过应用欧盟 H2020 项目 BIORIMA 开发的基于软件的决策支持系统（DSS），评估用作磁共振成像（MRI）造影剂的 PLGA-b-PEG-COOH 涂层的磁铁矿（FeO）纳米粒子的职业风险，以此来增加这方面的知识。职业风险评估是根据监管要求进行的，并使用危险和暴露评估的最先进模型，这些模型是 DSS 的一部分。使用来自文献的数据、来自合作行业的投入以及分发给医疗保健专业人员（即从事 MRI 造影剂工作的医生、护士和技术人员）的问卷的结果，为每个生命周期阶段开发了暴露场景。暴露浓度是从文献中的体内危险数据通过 APROBA 工具从预测性暴露模型或专门为此研究设计的监测活动中获得的。从文献中的体内危险数据出发，通过 APROBA 工具计算出无效应水平（DNEL）。使用暴露估计/测量值和 DNEL 对制定的暴露场景进行概率风险特征描述，包括不确定性分析。结果表明，除了在一种情况下需要采取特定的风险管理措施后才可以接受风险之外，在所有暴露场景中，作为肿瘤细胞诊断造影剂使用的磁铁矿 NBM 的生命周期中，工人面临的风险可以忽略不计。该研究还展示了使用 BIORIMA DSS 量化和交流纳米生物医学应用的职业风险及其相关不确定性的附加值。
