纳米碳酸钙的人体暴露途径及其潜在健康风险研究
Study on Human Exposure Pathways and Potential Health Risks of Nano-Calcium Carbonate
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摘要: 纳米碳酸钙是指粒径在1～100 nm之间的碳酸钙颗粒，它因具有某些特殊性质，如量子尺寸效应、表面效应等而被广泛用于橡胶工业、食品加工业、化妆品及医药领域。随着纳米碳酸钙的生产和使用，它们大量进入生态系统，并通过呼吸道、消化道和皮肤等途径进入人体，从而引起人们对其潜在健康风险的关注。目前很多研究报道，纳米碳酸钙在细胞水平及动物体内均具有一定的毒性作用，但大多只是针对单一的暴露途径进行分析，毒性机制也各不相同，并没有明确定论。因此，基于碳酸钙这类本身无毒或低毒性纳米颗粒的研究，本综述详细阐述纳米碳酸钙通过不同途径进入体内的转运代谢过程、体内外毒性作用和可能的毒性机制，为评估纳米碳酸钙的生物安全性提供新思路。Abstract: Nano-calcium carbonate refers to the calcium carbonate particles with size between 1~100 nm. Due to its special properties such as quantum size effect and surface effect, nano-calcium carbonate widely adopted in rubber industry, food processing, cosmetics and medicine synthesis. With the extensive production and application, a large amount of nano-calcium carbonate comes into the ecosystem, and further enters the human body through respiratory tract, digestive tract and skin, thus arousing people's attention to their potential health risks. At present, many studies have reported that nano-calcium carbonate shows a certain toxic effect at the cellular level as well as in animals. However, most of them only analyzed a single exposure route and provided different toxicity mechanisms without clear determinism. Therefore, based on the research of calcium carbonate, non-toxic or low-toxic nano-particles, this review introduces the transport and metabolism process, in vitro and in vivo toxicity and possible toxicity mechanism through different pathways in detail. The current research is expected to provide a new idea for evaluating the biological safety of nano-calcium carbonate.
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Prietl B, Meindl C, Roblegg E, et al. Nano-sized and micro-sized polystyrene particles affect phagocyte function[J]. Cell Biology and Toxicology, 2014, 30(1):1-16 Yao M F, He L L, McClements D J, et al. Uptake of gold nanoparticles by intestinal epithelial cells:Impact of particle size on their absorption, accumulation, and toxicity[J]. Journal of Agricultural and Food Chemistry, 2015, 63(36):8044-8049 Mishra S, Sonawane S H, Singh R P. Studies on characterization of nano CaCO3 prepared by thein situ deposition technique and its application in PP-nano CaCO3 composites[J]. Journal of Polymer Science Part B:Polymer Physics, 2005, 43(1):107-113 陈璇, 章家恩, 危晖. 环境微塑料的迁移转化及生态毒理学研究进展[J]. 生态毒理学报, 2021, 16(6):70-86 Chen X, Zhang J E, Wei H. Research progress and prospect on transportation, transformation and ecotoxicology of microplastics in environment[J]. Asian Journal of Ecotoxicology, 2021, 16(6):70-86(in Chinese)
Blinova I, Ivask A, Heinlaan M, et al. Ecotoxicity of nanoparticles of CuO and ZnO in natural water[J]. Environmental Pollution, 2010, 158(1):41-47 Feng X L, Chen A J, Zhang Y L, et al. Central nervous system toxicity of metallic nanoparticles[J]. International Journal of Nanomedicine, 2015, 10:4321-4340 Epple M. Review of potential health risks associated with nanoscopic calcium phosphate[J]. Acta Biomaterialia, 2018, 77:1-14 Kim T H, Kim M, Park H S, et al. Size-dependent cellular toxicity of silver nanoparticles[J]. Journal of Biomedical Materials Research Part A, 2012, 100A(4):1033-1043 Voigt N, Henrich-Noack P, Kockentiedt S, et al. Surfactants, not size or zeta-potential influence blood-brain barrier passage of polymeric nanoparticles[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2014, 87(1):19-29 Tsai C J, Huang C Y, Chen S C, et al. Exposure assessment of nano-sized and respirable particles at different workplaces[J]. Journal of Nanoparticle Research, 2011, 13(9):4161-4172 Yang W, Peters J I, Williams R O 3rd. Inhaled nanoparticles:A current review[J]. International Journal of Pharmaceutics, 2008, 356(1-2):239-247 Bakand S, Hayes A, Dechsakulthorn F. Nanoparticles:A review of particle toxicology following inhalation exposure[J]. Inhalation Toxicology, 2012, 24(2):125-135 Braakhuis H M, Park M V, Gosens I, et al. Physicochemical characteristics of nanomaterials that affect pulmonary inflammation[J]. Particle and Fibre Toxicology, 2014, 11:18 李聪, 吴奇峰, 谭玉莲, 等. 纳米碳酸钙与矽尘对作业工人肺功能影响的对比[J]. 中国工业医学杂志, 2016, 29(2):110-112 Li C, Wu Q F, Tan Y L, et al. A comparative study on pulmonary function of workers exposed to nano-calcium carbonate and silica dusts[J]. Chinese Journal of Industrial Medicine, 2016, 29(2):110-112(in Chinese)
Arredouani M, Yang Z P, Ning Y Y, et al. The scavenger receptor MARCO is required for lung defense against pneumococcal pneumonia and inhaled particles[J]. The Journal of Experimental Medicine, 2004, 200(2):267-272 Gumbleton M. Caveolae as potential macromolecule trafficking compartments within alveolar epithelium[J]. Advanced Drug Delivery Reviews, 2001, 49(3):281-300 Buzea C, Pacheco I I, Robbie K. Nanomaterials and nanoparticles:Sources and toxicity[J]. Biointerphases, 2007, 2(4):MR17-MR71 胡博骅. 纳米碳酸钙在裸鼠体内的分布特征及对大鼠脏器损伤的病理学研究[D]. 太原:山西医科大学, 2014:6-18 Hu B H. Distribution of nano-CaCO3 in mice and the pathological observation of the mice organs injury[D]. Taiyuan:Shanxi Medical University, 2014 :6-18(in Chinese)
卢金锁, 陈诚, 李雄, 等. 饮用水水垢问题辨析[J]. 中国给水排水, 2019, 35(8):15-19 Lu J S, Chen C, Li X, et al. Analysis of scale problem in drinking water[J]. China Water & Wastewater, 2019, 35(8):15-19(in Chinese)
Lee J A, Kim M K, Kim H M, et al. The fate of calcium carbonate nanoparticles administered by oral route:Absorption and their interaction with biological matrices[J]. International Journal of Nanomedicine, 2015, 10:2273-2293 Hoet P H, Brüske-Hohlfeld I, Salata O V. NPs-known and unknown health risks[J]. Journal of Nanobiotechnology, 2005, 2(1):12 Kim M K, Lee J A, Jo M R, et al. Cytotoxicity, uptake behaviors, and oral absorption of food grade calcium carbonate nanomaterials[J]. Nanomaterials, 2015, 5(4):1938-1954 Meng N, Han L, Pan X H, et al. Nano-Mg(OH)2-induced proliferation inhibition and dysfunction of human umbilical vein vascular endothelial cells through caveolin-1-mediated endocytosis[J]. Cell Biology and Toxicology, 2015, 31(1):15-27 Filipe P, Silva J N, Silva R, et al. Stratum corneum is an effective barrier to TiO2 and ZnO nanoparticle percutaneous absorption[J]. Skin Pharmacology and Physiology, 2009, 22(5):266-275 Parayanthala Valappil M, Santhakumar S, Arumugam S. Determination of oxidative stress related toxicity on repeated dermal exposure of hydroxyapatite nanoparticles in rats[J]. International Journal of Biomaterials, 2014, 2014:476942 Vogt A, Rancan F, Ahlberg S, et al. Interaction of dermatologically relevant nanoparticles with skin cells and skin[J]. Beilstein Journal of Nanotechnology, 2014, 5:2363-2373 Cevc G, Vierl U. Nanotechnology and the transdermal route:A state of the art review and critical appraisal[J]. Journal of Controlled Release:Official Journal of the Controlled Release Society, 2010, 141(3):277-299 Monteiro-Riviere N A, Wiench K, Landsiedel R, et al. Safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in UVB sunburned skin:An in vitro and in vivo study[J]. Toxicological Sciences:An Official Journal of the Society of Toxicology, 2011, 123(1):264-280 柯学, 许颖, 佘佐彦. 纳米级与微米级珍珠粉中碳酸钙对离体小鼠皮肤渗透性的研究[J]. 中国新药与临床杂志, 2006, 25(1):25-28 Ke X, Xu Y, She Z Y. Study of transdermal permeability on mouse skin in vitro about calcium carbonate in micro and nano pearl powder[J]. Chinese Journal of New Drugs and Clinical Remedies, 2006, 25(1):25-28(in Chinese)
Kopp M, Kollenda S, Epple M. Nanoparticle-protein interactions:Therapeutic approaches and supramolecular chemistry[J]. Accounts of Chemical Research, 2017, 50(6):1383-1390 Treuel L, Brandholt S, Maffre P, et al. Impact of protein modification on the protein corona on nanoparticles and nanoparticle-cell interactions[J]. ACS Nano, 2014, 8(1):503-513 Sonmez E, Cacciatore I, Bakan F, et al. Toxicity assessment of hydroxyapatite nanoparticles in rat liver cell model in vitro[J]. Human & Experimental Toxicology, 2016, 35(10):1073-1083 Tada-Oikawa S, Eguchi M, Yasuda M, et al. Functionalized surface-charged SiO2 nanoparticles induce pro-inflammatory responses, but are not lethal to caco-2 cells[J]. Chemical Research in Toxicology, 2020, 33(5):1226-1236 Hong T K, Tripathy N, Son H J, et al. A comprehensive in vitro and in vivo study of ZnO nanoparticles toxicity[J]. Journal of Materials Chemistry B, 2013, 1(23):2985-2992 Gossmann R, Spek S, Langer K, et al. Didodecyldimethylammonium bromide (DMAB) stabilized poly(lactic-co-glycolic acid) (PLGA) nanoparticles:Uptake and cytotoxic potential in Caco-2 cells[J]. Journal of Drug Delivery Science and Technology, 2018, 43:430-438 McCracken C, Zane A, Knight D A, et al. Minimal intestinal epithelial cell toxicity in response to short- and long-term food-relevant inorganic nanoparticle exposure[J]. Chemical Research in Toxicology, 2013, 26(10):1514-1525 He B, Lin P, Jia Z R, et al. The transport mechanisms of polymer nanoparticles in Caco-2 epithelial cells[J]. Biomaterials, 2013, 34(25):6082-6098 Schaeublin N M, Braydich-Stolle L K, Schrand A M, et al. Surface charge of gold nanoparticles mediates mechanism of toxicity[J]. Nanoscale, 2011, 3(2):410-420 陶一凡, 张小强, 李琪, 等. 纳米二氧化钛对小胶质细胞Notch信号通路及炎症因子分泌水平的影响[J]. 生态毒理学报, 2021, 16(2):212-218 Tao Y F, Zhang X Q, Li Q, et al. Effects of nano-titanium dioxide on Notch signaling pathway and secretion of inflammatory factors in microglia[J]. Asian Journal of Ecotoxicology, 2021, 16(2):212-218(in Chinese)
张淑华, 王翼飞, 甄亚平, 等. 不同粒径碳酸钙对HCT-8细胞的氧化损伤作用[J]. 毒理学杂志, 2013, 27(6):427-430 Zhang S H, Wang Y F, Zhen Y P, et al. The oxidative damage caused by different sizes of calcium carbonate particles in HCT-8 cells[J]. Journal of Toxicology, 2013, 27(6):427-430(in Chinese)
程志斌, 刘艳菊, 郭青云, 等. 柴油车尾气亚慢性暴露致小鼠肺部炎症反应、氧化损伤和细胞凋亡的作用研究[J]. 生态毒理学报, 2021, 16(4):280-291 Cheng Z B, Liu Y J, Guo Q Y, et al. Subchronic exposure to diesel engine exhaust induced pulmonary inflammation response, oxidative stress and cell apoptosis in mice[J]. Asian Journal of Ecotoxicology, 2021, 16(4):280-291(in Chinese)
刘明, 黄振烈, 梁丽红, 等. 纳米碳酸钙对人表皮细胞氧化应激和凋亡的影响[J]. 热带医学杂志, 2016, 16(11):1353-1357 Liu M, Huang Z L, Liang L H, et al. Oxidative stress and apoptosis of HaCaT induced by nano calcium carbonate[J]. Journal of Tropical Medicine, 2016, 16(11):1353-1357(in Chinese)
d'Amora M, Liendo F, Deorsola F A, et al. Toxicological profile of calcium carbonate nanoparticles for industrial applications[J]. Colloids and Surfaces B, Biointerfaces, 2020, 190:110947 Tabei Y, Sugino S, Eguchi K, et al. Effect of calcium carbonate particle shape on phagocytosis and pro-inflammatory response in differentiated THP-1 macrophages[J]. Biochemical and Biophysical Research Communications, 2017, 490(2):499-505 宋秋坤. 纳米碳酸钙肺毒性的实验研究[D]. 太原:山西医科大学, 2011:16-30 Song Q K. Study on pulmonary toxicity of nanoparticles of calcium carbonate[D]. Taiyuan:Shanxi Medical University, 2011:16 -30(in Chinese)
许伊, 杨士红, 尤国祥, 等. 纳米二氧化铈的潜在生态风险及毒性作用机制研究进展[J]. 生态毒理学报, 2021, 16(1):43-55 Xu Y, Yang S H, You G X, et al. Review of the potential ecological risks and toxicity mechanisms of nanoceria[J]. Asian Journal of Ecotoxicology, 2021, 16(1):43-55(in Chinese)
Sung J H, Park S J, Jeong M S, et al. Physicochemical analysis and repeated-dose 90-days oral toxicity study of nanocalcium carbonate in Sprague-Dawley rats[J]. Nanotoxicology, 2015, 9(5):603-612 Huang S, Chen J C, Hsu C W, et al. Effects of nano calcium carbonate and nano calcium citrate on toxicity in ICR mice and on bone mineral density in an ovariectomized mice model[J]. Nanotechnology, 2009, 20(37):375102 Jaji A Z, Zakaria Z A B, Mahmud R, et al. Safety assessments of subcutaneous doses of aragonite calcium carbonate nanocrystals in rats[J]. Journal of Nanoparticle Research:An Interdisciplinary Forum for Nanoscale Science and Technology, 2017, 19(5):175 宋秋坤, 王慧, 贺连平, 等. 纳米碳酸钙对大鼠精子畸形和外周血淋巴细胞DNA的影响[J]. 毒理学杂志, 2010, 24(2):112-115 Song Q K, Wang H, He L P, et al. The effect of nano-CaCO3 on sperm and peripheral blood lymphocytes DNA of rats[J]. Journal of Toxicology, 2010, 24(2):112-115(in Chinese)
刘卫花, 胡博骅, 冯涓, 等. 纳米碳酸钙亚慢性染毒对大鼠神经行为的影响[J]. 环境与职业医学, 2014, 31(5):373-376 Liu W H, Hu B H, Feng J, et al. Neurobehavior of rats following subchronic exposure to calcium carbonate nanoparticles[J]. Journal of Environmental & Occupational Medicine, 2014, 31(5):373-376(in Chinese)
胡博骅, 刘卫花, 冯涓, 等. 亚慢性染毒纳米碳酸钙大鼠组织病理学研究[J]. 毒理学杂志, 2014, 28(2):91-94 Hu B H, Liu W H, Feng J, et al. The histopathological change in organs of rats sub-chronic exposed to nano-calcium carbonate[J]. Journal of Toxicology, 2014, 28(2):91-94(in Chinese)
钱怡. 纳米碳酸钙对机体抗氧化系统及炎性细胞因子的影响[D]. 太原:山西医科大学, 2014:15-22 Qian Y. Effect of nano-calcium carbonate on the body's antioxidant system and inflammatory cytokines[D]. Taiyuan:Shanxi Medical University, 2014:15 -22(in Chinese)
仇玉兰, 宋秋坤, 王慧, 等. 纳米碳酸钙对大鼠亚慢性肺毒性作用[J]. 中国公共卫生, 2011, 27(4):451-453 Qiu Y L, Song Q K, Wang H, et al. Subchronic pulmonary toxicity of nano-sized calcium carbonate in rats[J]. Chinese Journal of Public Health, 2011, 27(4):451-453(in Chinese)
王慧, 宋秋坤, 刘风琴, 等. 纳米碳酸钙和微米碳酸钙亚急性染毒对大鼠肺组织的毒性作用[J]. 环境与健康杂志, 2011, 28(5):390-392 , 471 Wang H, Song Q K, Liu F Q, et al. Toxic effects of subacute exposure to nano-sized and micro-sized calcium carbonate on lung in rats[J]. Journal of Environment and Health, 2011, 28(5):390-392, 471(in Chinese)
邵春燕, 付文亮, Md Zuki Bin Abu Bakar Zakaria. 海扇壳源性碳酸钙纳米微粒对大鼠的急性毒性作用[J]. 吉林大学学报(医学版), 2019, 45(3):524-530 Shao C Y, Fu W L, Md Zuki Bin Abu Bakar Zakaria. Acute toxicity of cockle shell-derived calcium carbonate nanoparticles on rats[J]. Journal of Jilin University (Medicine Edition), 2019, 45(3):524-530(in Chinese) 石岩峰. 浅论饮用水中硬度对人体健康的影响[J]. 农业与技术, 2012, 32(2):193 Shi Y F. Influence of hardness in drinking water on human health[J]. Agriculture and Technology, 2012 , 32(2):193(in Chinese)
冯涓, 刘卫花, 钱怡, 等. 纳米碳酸钙对职业暴露人群的血液和心血管系统的影响[J]. 环境与职业医学, 2014, 31(5):377-380 Feng J, Liu W H, Qian Y, et al. Effects of occupational exposure to nano-CaCO3 on hematological and cardiovascular systems[J]. Journal of Environmental & Occupational Medicine, 2014, 31(5):377-380(in Chinese)
梁丽红. 纳米碳酸钙对作业人群健康影响的初步研究[D]. 广州:南方医科大学, 2014:43-50 Liang L H. Preliminary study on the health effects of workers exposed to nano calcium carbonate[D]. Guangzhou:Southern Medical University, 2014:43 -50(in Chinese)
Li G L, Liang L H, Yang J C, et al. Pulmonary hypofunction due to calcium carbonate nanomaterial exposure in occupational workers:A cross-sectional study[J]. Nanotoxicology, 2018, 12(6):571-585 Franck U, Odeh S, Wiedensohler A, et al. The effect of particle size on cardiovascular disorders:The smaller the worse[J]. The Science of the Total Environment, 2011, 409(20):4217-4221 林道辉, 冀静, 田小利, 等. 纳米材料的环境行为与生物毒性[J]. 科学通报, 2009, 54(23):3590-3604 Lin D H, Ji J, Tian X L, et al. Environmental behavior and toxicity of engineered nanomaterials[J]. Chinese Science Bulletin, 2009, 54(23):3590-3604(in Chinese)
Li Y B, Ju D W. The role of autophagy in nanoparticles-induced toxicity and its related cellular and molecular mechanisms[J]. Advances in Experimental Medicine and Biology, 2018, 1048:71-84 Devasagayam T P, Tilak J C, Boloor K K, et al. Free radicals and antioxidants in human health:Current status and future prospects[J]. The Journal of the Association of Physicians of India, 2004, 52:794-804 周小君, 徐仰辉, 何强, 等. 纳米颗粒对淡水藻类生长的影响:毒性机制与复合毒性[J]. 生态毒理学报, 2021, 16(3):128-143 Zhou X J, Xu Y H, He Q, et al. Effects of nanoparticles on growth of freshwater algae:Toxicity mechanism and combined toxicity[J]. Asian Journal of Ecotoxicology, 2021, 16(3):128-143(in Chinese)
宋益娟. 食品包装材料中纳米银对肠上皮细胞(Caco-2)安全性的研究[D]. 杭州:中国计量学院, 2014:11-37 Song Y J. Safety assessment of sliver nanoparticles in food packaging materials on human epithelial colorectal adenocarcinoma (caco-2) cells[D]. Hangzhou:China University of Metrology, 2014 :11-37(in Chinese)
Lin E, Gletsu-Miller N. Surgical stress induces an amplified inflammatory response in patients with type 2 diabetes[J]. ISRN Obesity, 2013, 2013:910586 Feng Y C, He D, Yao Z Y, et al. The machinery of macroautophagy[J]. Cell Research, 2014, 24(1):24-41 何付凡, 陈欢, 张玉彬. 纳米材料诱导细胞自噬的机制和生物学效应[J]. 药学研究, 2017, 36(4):226-230 He F F, Chen H, Zhang Y B. Nanomaterial-induced autophagy:Underlying mechanisms and functional consequences[J]. Journal of Pharmaceutical Research, 2017, 36(4):226-230(in Chinese)
Moosavi M A, Sharifi M, Ghafary S M, et al. Photodynamic N-TiO2 nanoparticle treatment induces controlled ROS-mediated autophagy and terminal differentiation of leukemia cells[J]. Scientific Reports, 2016, 6:34413 臧一腾, 张婷. 纳米材料诱导细胞自噬及其"双刃剑"作用[J]. 生态毒理学报, 2019, 14(5):65-73 Zang Y T, Zhang T. Research progress of autophagy and its function of "double-edged sword" induced by nanomaterials[J]. Asian Journal of Ecotoxicology, 2019, 14(5):65-73(in Chinese)
Cheng Y N, Zhang W B, Fan H, et al. Water-soluble nanopearl powder promotes MC3T3-E1 cell differentiation by enhancing autophagy via the MEK/ERK signaling pathway[J]. Molecular Medicine Reports, 2018, 18(1):993-1000 Liu Q, Luo Y, Zhao Y, et al. Nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells[J]. Bioactive Materials, 2022, 8:478-493 Ning F, Yang Z H, Xu L S, et al. Targeted tumor therapy by autophagy of nanoparticles[J]. Future Oncology, 2020, 16(12):793-803 Lee Y H, Cheng F Y, Chiu H W, et al. Cytotoxicity, oxidative stress, apoptosis and the autophagic effects of silver nanoparticles in mouse embryonic fibroblasts[J]. Biomaterials, 2014, 35(16):4706-4715 刘鑫, 陈洁, 朱永生, 等. 自噬对钙化性纳米微粒致肾结石形成的作用机制[J]. 医学研究生学报, 2020, 33(1):44-49 Liu X, Chen J, Zhu Y S, et al. Mechanism of autophagy on the formation of kidney stones caused by calcified nanoparticles[J]. Journal of Medical Postgraduates, 2020, 33(1):44-49(in Chinese)
Wang S, Ni D Z, Yue H, et al. Exploration of antigen induced CaCO3 nanoparticles for therapeutic vaccine[J]. Small, 2018, 14(14):e1704272 -
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