计算毒理学工具解码纳米毒性评估和毒性机理  

In silico tools in computational toxicology decode risk assessment and mechanism interpretation of nanomaterials

作　　者：黄杨 吴雨宣 伍天翔 王天勤 李雪花[2] 张洪武 HUANG Yang;WU Yuxuan;WU Tianxiang;WANG Tianqin;LI Xuehua;ZHANG Hongwu(School of Chemistry and Materials Science,Ludong University,Yantai,264025,China;Key Laboratory of Industrial Ecology and Environmental Engineering(MOE),School of Environmental Science and Technology,Dalian University of Technology,Dalian,116024,China)

机构地区：[1]鲁东大学化学与材料科学学院,烟台264025 [2]工业生态与环境工程教育部重点实验室,大连理工大学环境学院,大连116024

出　　处：《环境化学》2025年第3期764-776,共13页Environmental Chemistry

基　　金：国家自然科学基金(22176023);烟台市高端人才引育“双百计划”;鲁东大学研究生创新项目(119-810201)资助

摘　　要：“十四五”时期对“重视新污染物治理”提出了新的要求.工程纳米材料等新污染物的毒性筛查对于保护环境和人类健康至关重要.由于动物实验方法面临周期长、成本高、效率低下、伦理问题等局限性,传统毒理学实验的进行速度远远落后于新纳米材料的出现速度.为了高通量、低成本地评估纳米材料潜在的健康风险,发展动物实验的替代方法十分必要.计算毒理学工具作为最有望替代动物实验的智能策略之一,仍处于积极发展和应用的早期阶段.本文使用VOSviewer软件对近十年来代表性的纳米计算毒理学研究进行了分析,综述了用于筛查和评估纳米材料毒性、解释其毒性机理的各种计算毒理学工具,包括机器学习模型和分子模拟等.本文讨论的终点包括纳米材料与各类生物界面的作用、肺毒性、肾毒性、生殖发育毒性和神经毒性等,并总结了影响各类毒性的关键参数,提出了该领域发展中存在的问题与展望,有望为纳米材料的计算毒理学研究和应用提供参考.During the 14th Five Year Plan period from 2021 to 2025,new requirements were put forward for"attaching importance to the treatment of emerging contaminants".Risk assessment of engineered nanomaterials and other emerging contaminants is of great importance for protecting human health and the environment.Traditional hazard assessment relies mostly on in vivo testing that poses technical challenges,e.g.,regarding the validity of extrapolation to humans,ethical dilemmas,but also comes with high resource demands in cost and time.Non-testing approaches in hazard assessment is necessary,considering cost and time efficiency to assess potential risks.Computational toxicology tools are alternative methods in compliance with the 3R(Replacement,Reduction,and Refinement)principles for reducing the use of animals in research.The advances in in silico tools for toxicity assessment are essential for increasing throughput,reducing the burden of animal testing,providing details of the toxicity mechanisms,and generating novel hypotheses for risk assessment in nano-toxicity.Computational toxicology tools comprise an active and diverse collection of ongoing efforts,although it is still in their early steps toward a scientific accord,subsequent guidelines,and regulation adoption.During the critical juncture,this paper reviews diverse in silico tools including machine learning models and molecular simulations for predicting biomacromolecule interactions and the adverse effects of nanomaterials during the last decade.Computational toxicology for analyzing and simulating various toxicity endpoints such as pulmonary toxicity,nephrotoxicity,reproductive toxicity,neurotoxicity,etc.are discussed,the characteristics affecting toxicity are deeply understood.The in silico approaches used as alternatives to animal models are helping to address the ethical,economic,and time constraints of in vivo tests,while also advancing understanding of toxicity mechanisms.In the future,specialized comprehensive databases of engineered nanomaterials and other

关 键 词：新污染物 计算毒理学 纳米材料 机器学习 分子模拟. 

分 类 号：X-1[环境科学与工程] O6[理学—化学]