用于监管毒理学的基于生理学的纳米材料数学模型:综述

Physiologically based mathematical models of nanomaterials for regulatory toxicology: A review.

作者信息

Lamon L, Asturiol D, Vilchez A, Cabellos J, Damásio J, Janer G, Richarz A, Worth A

机构信息

European Commission, Joint Research Centre, Ispra (VA), Italy.

Leitat Technological Center, c/de la Innovació 2, Terrassa, Barcelona, Spain.

出版信息

Comput Toxicol. 2019 Feb;9:133-142. doi: 10.1016/j.comtox.2018.10.002.

Abstract

The development of physiologically based (PB) models to support safety assessments in the field of nanotechnology has grown steadily during the last decade. This review reports on the availability of PB models for toxicokinetic (TK) and toxicodynamic (TD) processes, including and dosimetry models applied to manufactured nanomaterials (MNs). In addition to reporting on the state-of-the-art in the scientific literature concerning the availability of physiologically based kinetic (PBK) models, we evaluate their relevance for regulatory applications, mainly considering the EU REACH regulation. First, we performed a literature search to identify all available PBK models. Then, we systematically reported the content of the identified papers in a tailored template to build a consistent inventory, thereby supporting model comparison. We also described model availability for physiologically based dynamic (PBD) and and dosimetry models according to the same template. For completeness, a number of classical toxicokinetic (CTK) models were also included in the inventory. The review describes the PBK model landscape applied to MNs on the basis of the type of MNs covered by the models, their stated applicability domain, the type of (nano-specific) inputs required, and the type of outputs generated. We identify the main assumptions made during model development that may influence the uncertainty in the final assessment, and we assess the REACH relevance of the available models within each model category. Finally, we compare the state of PB model acceptance for chemicals and for MNs. In general, PB model acceptance is limited by the absence of standardised reporting formats, psychological factors such as the complexity of the models, and technical considerations such as lack of blood:tissue partitioning data for model calibration/validation.

摘要

在过去十年中,用于支持纳米技术领域安全评估的基于生理的(PB)模型稳步发展。本综述报告了用于毒代动力学(TK)和毒效动力学(TD)过程的PB模型的可用性,包括应用于人造纳米材料(MN)的剂量学模型。除了报告科学文献中关于基于生理的动力学(PBK)模型可用性的最新情况外,我们还评估了它们在监管应用中的相关性,主要考虑欧盟的《化学品注册、评估、授权和限制法规》(REACH)。首先,我们进行了文献检索以识别所有可用的PBK模型。然后,我们在一个定制的模板中系统地报告已识别论文的内容,以构建一个一致的清单,从而支持模型比较。我们还根据相同的模板描述了基于生理的动态(PBD)模型以及剂量学模型的可用性。为了完整性,清单中还包括了一些经典毒代动力学(CTK)模型。本综述根据模型所涵盖的MN类型、其规定的适用领域、所需的(纳米特异性)输入类型以及生成的输出类型,描述了应用于MN的PBK模型概况。我们确定了模型开发过程中可能影响最终评估不确定性的主要假设,并评估了每个模型类别中可用模型与REACH的相关性。最后,我们比较了化学品和MN的PB模型接受情况。一般来说,PB模型的接受受到缺乏标准化报告格式、诸如模型复杂性等心理因素以及诸如缺乏用于模型校准/验证的血组织分配数据等技术因素的限制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c76/6472634/cbb9773d5bc5/gr1.jpg

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