Research Progress on Environmental Exposure and Human Health Effects of Microplastics
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摘要: 作为一种新型的全球性环境污染物，微塑料日益引起关注. 人体可通过摄食等途径摄入微塑料，进而引起潜在健康风险. 目前有关微塑料的研究日益增加，但关于人体微塑料暴露水平及其潜在健康危害方面的相关研究有限. 本文在梳理微塑料的人体暴露途径及水平的基础上，从体内、体外两方面试验研究总结分析了微塑料暴露对细胞、哺乳模式动物小鼠组织的影响，结果表明：①人类可通过消化道、呼吸道以及皮肤接触的方式摄入微塑料，其中经口摄入是最主要的接触途径. ②在人体多种组织、器官及代谢物中均检测到微塑料的存在，范围为0~134.3个/g. ③动物试验表明，微塑料可以通过血液循环蓄积于心、肝、脾、肺、肾和睾丸等器官中，引起炎症反应、氧化应激、免疫损伤、菌群失调、代谢紊乱等，甚至可能产生跨代效应. ④细胞试验表明，粒径较小的微塑料可穿透细胞膜进入细胞质中，引起细胞形态及功能改变，导致细胞活力下降，影响细胞生长与增殖，还可诱导ROS生成甚至产生DNA损伤等细胞毒性作用. 微塑料的毒性作用可能与其类型、粒径、染毒浓度及受试物类型等有关，建议今后加强环境低浓度下微塑料及其吸附物质在食物链传递过程中毒性蓄积与变化的研究，以及开展流行病学调查，为将来进一步阐释微塑料潜在的毒理机制和评估人体健康风险提供理论依据.Abstract: As a new type of global environmental pollutant, microplastics have attracted increasing attention. However, there is still a lack of research on exposure levels to microplastics and their potential health hazards. This review aims to sort out the pathways and levels of human exposure to microplastics, and to summarize the adverse effects of microplastic exposure on mammalian model animals-mice from in vivo and cultured cells in vitro. The results showed that: (1) Humans can ingest microplastics through digestive tract, respiratory tract, and skin contact, and oral ingestion is the main route of exposure. (2) Microplastics are detected in various tissues, organs, and metabolites of the human body, ranging from 0 to 134.3 per gram. (3) Animal experiments have shown that microplastics can accumulate in the heart, liver, spleen, lung, kidney, testis and other organs through blood circulation, causing inflammatory response, oxidative stress, immune damage, flora disorder, metabolic disorders, and even intergenerational effects. (4) Cell experiments have shown that microplastics with small particle sizes can penetrate cell membrane and enter the cytoplasm, causing changes in cell morphology and function, resulting in decreased cell vitality, affecting cell growth and proliferation, and inducing ROS generation and even DNA damage and other cytotoxic effects. The toxicity of microplastics may be related to its type, particle size, concentration and type of test substance. Further studies on toxic accumulation and changes of microplastics and their adsorbents in the food chain transfer process at low environmental concentrations can be strengthened, as well as epidemiological studies, to provide a theoretical basis for further elucidating the potential toxicological mechanisms of microplastics and assessing human health risks in the future.
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Key words:
- microplastics /
- exposure /
- health hazards /
- toxic effects
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表 1 微塑料人体内暴露情况
Table 1. Exposure of microplastics in human body
样本类型 样本来源 检测方法 微塑料丰度 微塑料主要类型 数据来源 代谢物 中国江苏无锡市的8名33~65岁的健康志愿者的人类粪便样本 FTIR 2个/g PP、PET 文献[25] 中国北京市24名年轻男性的粪便样本 FTIR 1~36个/g PET、PS、PE、PVC 文献[28] 中国香港8名居民粪便样本 Raman 50个/g PS、PP、PE 文献[29] 中国江苏南京市某医院50名健康参与者和52名炎症性肠病(IBD)患者的粪便样本 Raman 健康者28.0个/g，IBD患者41.8个/g PET、PA 文献[39] 中国上海市18对母婴的胎粪样本 LDIR 51.4个/g PA、PU1) 文献[38] 意大利34名产妇的母乳样本 Raman 0~2.72个/g PE、PVC、PP 文献[26] 中国江苏南京市四家医院104名手术者的体液样本 Raman 2~38个/mL PP、PS、PTFE2) 文献[43] 血液系统 荷兰22名健康志愿者的血液样本 Py-GC/MS 1.6 μg/mL PET、PE、PS 文献[30] 中国江苏南京市某医院26名心血管手术患者的血栓 Raman 0~15个/样 Phthalocyanine3)、LDPE4) 文献[31] 呼吸系统 中国广东汕头市某医院22名患有不同呼吸系统疾病患者的人类痰液样本 LDIR，FTIR 3.95个/mL PU、PES5)、CPE6) 文献[32] 中国辽宁省8名室内和8名室外工人上呼吸道的痰液和鼻灌洗液样本 LDIR 痰液：室外102.9个/g，室内134.3个/g. 鼻灌洗液：室外0.8个/g，室内2.6个/g PVC、PA 文献[34] 英国13例人肺组织样本 FTIR (1.42±1.50)个/g PET、PP、PS 文献[36] 消化系统 德国6名肝硬化患者和5名没有潜在肝病的成人组织样本 Raman 1.2个/g PS、PVC、PET、PMMA7)、POM8)、PP 文献[37] 马来西亚11名成人的结肠切除手术样本 FTIR (28.1±15.4)个/g PC、PA、PP 文献[44] 生殖系统 中国上海市18对母婴的胎盘样本 LDIR 18个/g PA、PU 文献[38] 中国江苏无锡市的17个胎盘样本 LDIR (2.70±2.65)个/g PVC、PP、PBS9) 文献[24] 伊朗43名产妇的胎盘样本 Raman 2~38个/样本 PE、PS 文献[23] 注：1)PU—聚氨基甲酸酯；2)PTFE—聚四氟乙烯；3)Phthalocyanine—酞菁；4)LDPE—低密度聚乙烯；5)PES—聚醚砜；6)CPE—氯化聚乙烯；7)PMMA—聚甲基丙烯酸甲酯；8)POM—聚甲醛；9)PBS—聚丁二酸丁二醇酯. 
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表 2 微塑料对模式动物的健康影响
Table 2. Health effects of microplastics on model animals
微塑料类型 尺寸 剂量 染毒方式 染毒时间 生物学效应 数据来源 PS 5、50、100、200 µm 80 mg/kg(以体质量计) 灌胃 10周 胰岛素抵抗，肠道菌群改变 文献[45] PS 1~10、50~100 µm 10 mg/L 饮水 30 d ROS产生，破坏骨骼肌再生 文献[46] PS 0.5、50 µm 0.1、1 mg/L 饮水 5周 黏蛋白降低，肠道菌群失调，肝脂代谢紊乱 文献[47] PS 0.5、4、10 µm 1 mg/d 灌胃 4周 睾丸炎症，血睾屏障破坏 文献[48] PS 4、10 µm 20、40 mg/kg(以体质量计) 灌胃 4周 ROS产生，血睾屏障破坏 文献[49] PS 5.0~5.9 µm 0.01~1 mg/d 灌胃 6周 氧化应激，生殖毒性 文献[50] PS 5 µm 0.5 mg/L 饮水 4周 肠道炎症，黏膜损伤，菌群改变 文献[51] PS 5 µm 0.5 mg/L 饮水 4周 结肠炎症，脂质代谢紊乱 文献[52] PS 5 µm 0.1、1 mg/L 饮水 6周 肠黏液分泌减少，肠道屏障损伤 文献[53] PS 5 µm 12 mg/kg(以体质量计) 吸入 1周 肺泡上皮受损，肺纤维化，氧化应激 文献[54] PS 5 µm 0.1、0.5 mg/d 灌胃 4周 血液毒性，扰乱骨髓细胞功能 文献[55] PS 5 µm 0.1 mg/d 灌胃 43 d 氧化应激，生殖毒性 文献[56] PS 2 µm 0.2、0.4 mg/d 灌胃 4、8周 肾脏损伤，内质网应激，炎症标志物和自噬相关蛋白水平升高 文献[57] PS 1 µm 0.08 mg/kg(以体质量计) 饮水 4周 结肠炎症，加重关节炎 文献[58] PS 800 nm 30 mg/kg(以体质量计) 灌胃 5周 卵巢炎症，卵母质量降低 文献[59] PS 500 nm 0.5 mg/d 灌胃 4周 肝脏炎症，巨噬细胞极化，自然杀伤细胞浸润 文献[60] PS 500 nm 1 mg/L 饮水 90 d 肝脏损伤，氧化应激 文献[61] PS 50、500 nm 0.000 5~1 mg/d 饮食 胚胎第8天~出生后2周 跨代效应，神经发育缺陷 文献[62] PS 50 nm 0.5~50 mg/kg(以体质量计) 灌胃 1周 小胶质细胞活化，神经元损伤 文献[63] PS 20 nm 14.6 ng/kg(以体质量计) 饮水 30 d 红细胞DNA损伤 文献[64] PE 10~150 µm 0.006~0.6 mg/d 饲料 5周 肠道菌群失调，炎症 文献[65] PE 36、116 µm 100 mg/kg(以体质量计) 饲料 6周 肠道损伤，免疫反应，肠道菌群改变 文献[66] PE 40~48 µm 0.125~2 mg/d 灌胃 90 d 免疫损伤，脾脏内淋巴细胞亚群改变 文献[67] PE 1~10 µm 0.002、0.2 mg/kg(以体质量计) 灌胃 30 d 肠道菌群改变，黏蛋白降低，氨基酸代谢增加 文献[68] PVC 2 µm 100 mg/kg(以体质量计) 灌胃 60 d 肝脏损伤，肝脂代谢紊乱，肠道菌群失调 文献[69] PVC 2 µm 100 mg/kg(以体质量计) 灌胃 60 d 肠道黏液分泌降低，屏障功能障碍，肠道菌群失调 文献[70]
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表 3 微塑料对细胞的毒性效应
Table 3. Toxic effects of microplastics on cells
微塑料类型 粒径 暴露剂量 受试细胞 毒性效应 数据来源 PS 1、10 μm 0.1 mg/mL A549 抑制细胞增殖，细胞形态改变 文献[92] PS 5 μm 0.1 mg/mL Caco-2 细胞活力下降 文献[93] PS 4 μm 1 mg/cm2 BEAS-2B1) 细胞活力下降，氧化应激，炎症反应，肺上皮屏障破坏 文献[94] PS 0.1、5μm 0.2 mg/mL Caco-2 细胞摄取，ROS增加，线粒体去极化，抑制膜ABC转运蛋白活性 文献[95] PS 100、500 nm 0.1 mg/mL HUVECs 细胞活力下降，细胞膜损伤，诱导自噬 文献[96] PS 200 nm 0.1、0.2 mg/mL RAW264.7、BV22) 氧化应激，细胞膜完整性改变，溶酶体受损 文献[97] PS 100 nm 0.075 mg/mL Hs273) 刺激ROS产生，DNA损伤 文献[98] PS 44、100 nm 0.01 mg/mL AGS4) 内化，细胞质增加，细胞活力改变，炎症反应 文献[99] PS 40~90 nm 0.2 mg/mL Caco2/HT29、Caco2/HT29+Raji-B5) 细胞摄取，跨膜易位 文献[100] PS 75 nm 0.1 mg/mL BEAS-2B 自噬，内质网应激，细胞凋亡 文献[101] PS 60 nm 0.1 mg/mL LS174T、HT29、Caco-2 细胞凋亡 文献[102] PS 60 nm 0.02 mg/mL RAW264.7、BEAS-2B 诱导自噬，细胞凋亡，氧化应激 文献[103] PS 50 nm 0.3、8.1 μg/cm2 Calu-36)、THP-17) 细胞摄取，DNA损伤 文献[104] PS 50 nm 0.1 mg/mL SH-SY5Y 诱导神经突生长收缩，细胞形态改变和肿胀，细胞内成分溢出 文献[105] PS 20 nm 0.2 mg/mL PBMC8)、U9379)、THP-1、DMBM-210) 炎症反应，刺激细胞吞噬 文献[106] PE、PS 3~16 μm、10 μm 0.01 mg/mL T98G、HeLa11) 诱导ROS生成，氧化应激 文献[107] PP ~20 μm、25~200 μm 1 mg/mL PBMC、HMC-112)、
RBL-2H313)、RAW264.7炎症反应，免疫损伤 文献[108] PVC 136.5 μm >75 mg/mL Caco2、HepG2、HepaRG14) 细胞活力下降 文献[109] 注：1)BEAS-2B—人支气管上皮细胞；2)BV2—小鼠小胶质细胞；3)Hs27—人成纤维细胞；4)AGS—人胃腺癌细胞；5)Raji-B—人淋巴瘤细胞；6)Calu-3—人肺癌上皮细胞；7)THP-1—人急性单核细胞白血病细胞；8)PBMC—小鼠外周血单核细胞；9)U937—人淋巴瘤细胞；10)DMBM-2—小鼠单核巨噬细胞；11)HeLa—人宫颈癌细胞；12)HMC-1—人肥大细胞；13)RBL-2H3—人嗜碱性白血病细胞系；14)HepaRG—人肝癌细胞.
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