1-s2.0-S0304389422011542-main

Journal of Hazardous Materials 437 (2022) 129361
Contents lists available at ScienceDirect
Journal of Hazardous Materials

journal homepage: www.elsevier.com/locate/jhazmat
Review
Absorption, distribution, metabolism, excretion and toxicity of

microplastics in the human body and health implications
Pengfei Wu a, 1, Siyi Lin a, b, 1, Guodong Cao a, Jiabin Wu a, Hangbiao Jin c, Chen Wang d,
Ming Hung Wong e, Zhu Yang a, *, Zongwei Cai a, *
a
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China
b
State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern
University of Science and Technology, Shenzhen 518055, PR China
c
Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou,
Zhejiang 310014, PR China
d
State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, PR China
e
Consortium on Health, Environment, Education, and Research (CHEER), and Department of Science and Environmental Studies, The Education University of Hong
Kong, Hong Kong, China
H I G H L I G H T S G R A P H I C A L A B S T R A C T
• Absorption, distribution, metabolism,

excretion and toxicity of MPs are
discussed.
• The annual exposure from food, bever
ages, and air was estimated
quantitatively.
• The knowledge gaps and controversial
findings in MP study were highlighted.
• Data from a broad range of studies were
combined to create a comprehensive
picture.
• Health risks of MPs originate from the
particles and additives were implicated.
Abbreviations: AChE, Acetylcholinesterase; ADMET, Absorption, Distribution, Metabolism, Excretion and Toxicity; BFR, Brominated Flame Retardant; BP,
Bisphenol; DBP, Dibutyl phthalate; DEHP, Di(2-ethylhexyl)phthalate; DEP, Diethyl Phthalate; DMP, Dimethyl Phthalate; DnBP, Di-n-butyl Phthalate; DWTP, Drinking
Water Treatment Plant; EDI, Estimated Daily Intake; ER, Endoplasmic Reticulum; GR, Glutathione Reductase; GST, Glutathione S-transferase; GSH-Px, Glutathione
Peroxidase; HBCD, Hexabromocyclododecane; HOC, Hydrophobic Organic Compounds; IFN, Interferon; IL, Interleukin; MEHP, Mono-(2-ethylhexyl)phalate; MP,
Microplastic; NP, Nanoplastic; PBDE, polybrominated diphenyl ether; PC, Polycarbonate; PCB, Polychlorinated biphenyl; PE, Polyethylene; PET, Polyethene Tere
phthalate; PP, Polypropylene; PS, Polystyrene; PVC, Polyvinyl Chloride; ROS, Reactive Oxygen Species; SOD, Superoxide Dismutase; TCS, Triclosan; TNF, Tumor
Necrosis Factor; WHO, The World Health Organization; μ-FTIR, Micro-Fourier Transform Infrared Spectroscopy.
* Corresponding authors.
E-mail addresses: zyang@hkbu.edu.hk (Z. Yang), zwcai@hkbu.edu.hk (Z. Cai).
1
These authors contributed equally to this work
https://doi.org/10.1016/j.jhazmat.2022.129361
Received 25 March 2022; Received in revised form 8 June 2022; Accepted 9 June 2022
Available online 16 June 2022
0304-3894/© 2022 Elsevier B.V. All rights reserved.
P. Wu et al. Journal of Hazardous Materials 437 (2022) 129361
A R T I C L E I N F O A B S T R A C T
Editor: Dr. R Teresa Microplastics (MPs; <5 mm) in the biosphere draws public concern about their potential health impacts. Humans
are potentially exposed to MPs via ingestion, inhalation, and dermal contact. Ingestion and inhalation are the two
Keywords: major exposure pathways. An adult may consume approximately 5.1 × 103 items from table salts and up to 4.1 ×
Exposure Pathways 104 items via drinking water annually. Meanwhile, MP inhalation intake ranges from 0.9 × 104 to 7.9 × 104
Microplastics
items per year. The intake of MPs would be further distributed in different tissues and organs of humans
Nanoplastics
depending on their sizes. The excretion has been discussed with the possible clearance ways (e.g., urine and
Toxicity Assessments
Plasticizer feces). The review summarized the absorption, distribution, metabolic toxicity and excretion of MPs together
with the attached chemicals. Moreover, the potential implications on humans are also discussed from in vitro and
in vivo studies, and connecting the relationship between the physicochemical properties and the potential risks.
This review will contribute to a better understanding of MPs as culprits and/or vectors linking to potential
human health hazards, which will help outline the promising areas for further revealing the possible toxicity
pathways.
1. Introduction metabolization, unlike the reported “Trojan horse” effects of trans

ferring harmful chemicals into the animal body. Toxicological studies of
The plastic age has provided many conveniences in the current era. MPs in a variety of cell and animal models have been reported from
Still, only 21% of global plastic (over 368 million tonnes in 2019) have many laboratories. Exploring the technical discrepancies in their studies
been recycled or incinerated, with the remaining 79% discarded in the that might be associated with these dissimilar observations would likely
environment (Brown, 2019; Lebreton and Andrady, 2019). Due to their facilitate the clarification of the key features related to the MP toxicity.
durability, these wastes would continuously fragment under the “aging” Furthermore, the debate on the health risk of MPs had prolonged for
processes: ultraviolet radiation, temperature change, mechanical abra years, with the focus primarily on the severity of the current MP
sion, and biological effects (Dawson et al., 2018). Once broken into a contamination in the environment and whether the risk of MPs is
small scale (< 5 mm), the plastic waste is referred to the microplastics overstated (Backhaus and Wagner, 2020; Burton, 2017; Rist et al.,
(MPs), among which the ones with a size < 1 µm are specified as 2018). Quantitatively understanding how the chemical composition,
nanoplastics (NPs). MPs can be classified into primary and secondary size, concentration, and other physicochemical characteristics of MPs
MPs according to their origins. Primary MPs are intentionally manu affect their toxicity is crucial for resolving this debate.
factured in cosmetic products, while secondary MPs refer to those The present article estimated the ineluctable annual MP intake and
formed from the weathering degradation of textiles, tires, and more reviewed their potential distributions in the body. The fate of MPs in the
oversized plastic products (Wright and Kelly, 2017). human body was also examined for their physical, chemical, and bio
MP pollution has now been discovered widely in the hydrosphere, logical properties. Furthermore, we summarized the metabolism pro
atmosphere, lithosphere, and biosphere (Wright and Kelly, 2017). The cesses, along with the potential health risks, of MPs, as well as the
hydrosphere has been contaminated worldwide, including the coast endogenous/exogenous contaminants associated with them. The po
lines, polar regions, and Mariana Trench (Lebreton and Andrady, 2019). tential toxicities of MPs are inferred from the perspectives of oxidative
MPs in the hydrosphere mainly originated from land-based (e.g., road stress, inflammation, immune responses and neurological dysregulation
runoff, streams, wastewater effluents) and air-based sources (MPs using the combination of the current evidence from cell cultures and
conveyed by winds and atmospheric fallout) (Allen et al., 2019; Leb animal models. The essential knowledge gaps in our knowledge of MPs
reton et al., 2017). Through water-vapor exchanges, the concentration have yet to be filled, and limited data available represents high
of MPs (0.1–1 mm) can reach as high as 917 items⋅m-2⋅d-1 according to a discrepancy and low comparability. In this work, we critically reviewed
study in Vietnam (Dris et al., 2015). The terrestrial system is another these data and intended to create a comprehensive and quantitative
sink of MPs, 4- to 23-fold more than that in the marine environment, picture of the effects of MPs on the human body, albeit in a rough way.
with concentrations ranging from 300 to 67,500 mg⋅kg-1 (Scheurer and By exploring the human health implications, this review will contribute
Bigalke, 2018). to a deeper insight into MPs as perpetrators and/or vectors related to
As a result of their wide existence, their absorption, distribution, human health, which may help identify a promising field for additional
metabolism (along with the potential toxicity), and excretion (ADMET) detection on discovering more potential toxicity pathways influenced by
processes in humans have drawn increasing attention (Vethaak and MPs.
Legler, 2021). The known results suggested that individuals can inevi
tably intake MPs through ingestion, inhalation, and dermal contact. 2. Exposure routes of MPs into individuals
These MPs may affect human health by interfering with metabolic
processes. For years, scientists have been concerned about the potential Very recently, Leslie et al. (2022) recently detected MPs in human
health problems posed by MPs though no published research has directly blood, directly evidenced the providing direct evidence of MP exposure
documented the negative effects of MPs on humans. Nevertheless, the in the human being. It has long been believed that MPs could enter the
harmful impacts of MP exposure are still controversial and not yet fully human body via ingestion, inhalation, and dermal contact. Numerous
understood. Along with the accumulated documents about MP toxic studies examined foods/beverages, air, and daily consumables, but
ities, the investigations also found that MP exposures resulted in no or showed a big discrepancy in the abundance of MPs. In bottled water, for
very minor impacts. For example, inflammation is one of the most example, reported MP concentration ranged from 0 (e.g., undetectable)
commonly reported responses to MP exposure but it was also demon up to 107 items⋅L-1 (Mason et al., 2018; Zuccarello et al., 2019). Despite
strated that MPs triggered no inflammation at the cellular, organ, or the difference between samples and regions, technical diversities,
whole-body levels (Bunge et al., 2022; Stock et al., 2019). Would MPs including but not limited to those in the extraction processes, identifi
enhance or reduce the toxicity of the chemicals that they carry? Both cation approaches, and quantification methods also contributed signif
conclusions have been reached in different papers. Diepens and Koel icantly to the diverse results in the literature. The first and most
mans (2018), for instance, demonstrated that MP absorption reduced important gap in the field that needs to be filled is an international
the fraction of polycyclic aromatic hydrocarbons released for standard for MP detection and quantification. Besides comparing the MP
2
abundances among studies, the present section aims to draw a rough, yet According to Yap and Al-Mutairi (2022), humans consume seafood
comprehensive picture of MP exposure based on the preliminary and mainly through mollusks and fishes, in which the contamination of MPs
limited data. has been widely documented, as illustrated in Table 1. Reported MP
Furthermore, it is worthy to note that, more or less, the currently abundance in mollusks ranged from 0.18 ± 0.16 items⋅g-1 (in oysters)
available data underestimate the contamination levels of MPs. The (Phuong et al., 2018) to 13.1 items⋅g-1 (in mussels) (Leslie et al., 2017),
minimum size of MP particles that could be detected in an experimental while the maximum estimation went to 57.2 items⋅g-1 (in bivalves) (Li
approach is largely attributed to the technical limitations in extraction et al., 2015). Compared to the mollusks, the data from fish is little and
and identification. Considering the limitations in detection techniques, insufficient to evaluate the MP exposure through fish. Although a lot of
Lee et al. (2021) believed that a large proportion of MP items smaller reports on fish were published, these investigations mainly focused on
than a certain size, which they termed as “minimum cut-off size”, were the gastrointestinal tract of fish and documented a generally lower MP
not detected in the reported investigations. Accordingly, they reviewed abundance ranging between 0.02 and 15.4 items⋅fish-1 (Table 1).
the minimum size of MPs measured in various studies and estimated Moreover, the lower MP abundance in the fish gastrointestinal trace
human intake via table salt by building a strong relationship between might be caused by the discrepancy in the feeding strategies between
minimum cut-off sizes and logarithmic mean abundances. Once these organisms (Hantoro et al., 2019). The majority of the mollusks are
considering this correction is applied, the estimated mean yearly intake filter feeders with non-selective consumers, which are beneficial for
of MPs per capita increases four times (Fig. 1). Previous evidence ingesting MPs (<5 mm) (Wesch et al., 2016). Fishes, in contrast, are
accumulated from previous studies on nanoparticles, especially those selective feeders who reject/expel parts of MPs during the ingestion.
made of inert materials like plastics, indicates that the smaller MPs may Therefore, fishes unintentionally ingest less abundance of MPs from the
cause more severe toxicity in general. This incompleteness in the data is primary producers. Because the bioaccumulation of MPs has been
needed to be taken into account when assessing human risks of MP demonstrated (Santana et al., 2017), the detection and quantification of
exposure (Fig. 1). MPs inside fish bodies are highly desired for assessing the risk of fish
consumption.
Based on the levels of MPs detected from mollusks and the average
2.1. MP exposure to the human body through ingestion
consumption of 300 g per week EFSA (European Food Safety Authority),
2014, the estimated annual exposure of MPs via mollusks could be up to
2.1.1. Ingestion via seafood
~8.92 × 104 items (Fig. 1). For the intake from fishes, available esti
Along with the contamination of the marine environment, comes the
mation ranged from 518 to 4600 items⋅year-1, one order of magnitude
MP exposure via seafood. Through the trophic levels, MPs could be
lower than that from mollusks ((0.8–2.8)× 103 for adults and
transferred from primary to tertiary consumers. For example, Farrell and
(1.4–4.6)× 103 for children) (Akhbarizadeh et al., 2018; L. Barboza
Nelson (2013) observed that PS spheres with a diameter of 0.5 µm can be
et al., 2020). However, more accurate quantifications of MP content in
transferred from mussels (Mytilus edulis (L.)) to crabs (Carcinus maenas
fish should be obtained before we can consider fish as safer seafood.
(L.)), reaching 1.6 × 105 items in the entire hemolymph after 24 h.
Recent publications have evidenced the pollution of MPs along the
2.1.2. Ingestion via table salts
natural food chain (Lusher et al., 2015; Nelms et al., 2018). Beach
Table salts are necessary for everyday meals because they provide
hoppers (Platorchestia smithi) transferred the polyethylene (PE) MPs
critical components to human beings. Table salts gradually crystallize
(38–45 µm) to Krefft’s frillgobies (Bathygobius krefftii) with unclear
through the circulating and successive ponds under wind and sunlight
numbers and effects on fish personality (Elizalde-Velázquez et al., 2020;
(Yang et al., 2015). During the process, the produced table salts could
Tosetto et al., 2017). Bioaccumulation and biomagnification effects of
mix with the MPs breakdown from the ocean plastics or deposit from the
polyvinyl chloride (PVC) NPs (0.1–1 µm) from the mussels (Perna perna)
air (Kim et al., 2018). Their presence of MP in table salts varied signif
to fish (Spheoeroides greeleyi) were also reported (Santana et al., 2017).
icantly in different regions (Fig. 2 and Table S1). For example, according
to the results of sea salt MPs sized from 101 to 103 μm and detected by
the μ-FTIR Stereomicroscope, Croatia has a very high abundance of salt
MPs ((1.4–2.0) × 104 items⋅kg-1), China has the lowest quantity of
(5.5–6.8) × 102 item⋅kg-1, and Italy ((1.6–8.2) × 103 items⋅kg-1) has an
MP contamination in between (Fig. 1 & 2 and Table S1). Similarly, one
study investigated MP contamination in table salt among countries and
detected relatively high MP content in sea salts made from Asian regions
(1028 ± 3169 items⋅kg-1) than those from other continents (39 ± 9
items⋅kg-1) (Kim et al., 2018). Within the different Asian countries, the
MP abundance in sea salt varied from undetectable to 104 items⋅kg-1
(Kim et al., 2018). Also, this study discovered the positive correlations
between MPs in sea salts and their contents in an aquatic environment,
indicating that the MPs in salts might originate from the successive
breakdown of the plastics from the sea. Another study first examined the
Fig. 1. Estimation of human MP exposure from various sources. The maximum MP abundance in 15 different salt brands sold in Chinese supermarkets
(orange circles) and minimum (blue circles) values of the human exposure and found 550–681, 43–364, and 7–204 items⋅kg-1 in the sea, lake, and
levels were calculated using the average consumption of each source and MP rock salts, respectively (Yang et al., 2015). On the other hand, Karami
contamination levels measured experimentally in different samples. For plastic et al., (2017b) detected very similar levels of MPs (≤ 10 items⋅kg-1) from
packages, the MP determination was based on scanning electron microscopy 17 different salts purchased in eight countries (Australia, France, Iran,
with a size limitation of > 1 nm, while others were based on the common Japan, Malaysia, New Zealand, Portugal, and South Africa).
detection (μ-FTIR or μ-Ramam) with a size limitation of > 1 µm. Due to tech
The high MP contents in table salts indicate that salt consumption
nical limitations, the MP particles smaller than a certain level were missed in
might be one of the most crucial ways for MPs to enter the human body.
the current data. This underestimation could be corrected with technological
advancements or computational prediction (red question marks). The MP The World Health Organization (WHO) recommends that no more than
contamination in table salt, as an example, was corrected based on the corre 5 g of salts should be consumed in daily diets. According to this con
lation between logarithmic MP abundances and minimum sizes of MPs detected sumption level, it was estimated that adults can uptake 12.8–1242.8
(the open red circle) (Lee et al., 2021). items per year (Yang et al., 2015). However, the global average
3
Table 1
Occurrence of microplastics detected in seafood a.
Locations Species Concentration Shape Typesb References
(items⋅animal-1)
Asia (mollusks)
China, Coastline Blue Mussel 1.5–7.6 Fragment, Fiber PET, CP, PL (Li et al., 2015)
China, Shanghai Commercial Bivalves 4.3–57.2 Fragment, Fiber, N.A. (Li et al., 2016)
Pellet
Thailand, Gulf Rock Oyster 0.37–0.57 items⋅g-1 Fragment, Fiber PA, PET, PS (Thushari et al., 2017)
Europe (mollusks)
Belgium, Coastline Mussel 0.26–0.51 items⋅g-1 Fiber N.A. (De Witte et al., 2014)
Belgium, France, Mussel 0.2 items⋅g-1 Sphere PE, PS (Van Cauwenberghe and Janssen,
Netherlands 2014)
France, Atlantic coast Mussel 0.61 Fragment, Fiber PE, PP, PS, PL, PIB, (Phuong et al., 2018)
Nylon
France, Brittany Oyster 0.35–0.47 items⋅g-1 Sphere N.A. (Van Cauwenberghe and Janssen,
2014)
Germany, North Sea Mussel 0.24–0.36 items⋅g-1 Sphere N.A. (Van Cauwenberghe and Janssen,
2014)
Netherlands, North Sea Mussel, Crab, Oyster 13.1, 2.4–10.9, 2.5–3.8 Fiber, Sphere N.A. (Leslie et al., 2017)
items⋅g-1
Southern, North Sea Shrimp 1.23 Fiber N.A. (Devriese et al., 2015)
North America (mollusks)
Canada, British Clam 8.4–11.3 Fiber, Film, N.A. (Davidson and Dudas, 2016)
Fragment
Canada, Halifax Mussel 34–75 Fiber, Fragment PP, PET, PMMA (Mathalon and Hill, 2014)
The U.S.A, California Oyster 1.0 Fiber N.A. (Rochman et al., 2015)
Africa (fishes)
South Africa, Durban Mullet 3.8 Fragment, Fiber, PS, etc. (Naidoo et al., 2016)
Film
Asia (fishes)
China, Yangtze Anchovy, Garfish, Goby, etc. 1.1–7.2 Fragment, Fiber, CL, PET, PL (Jabeen et al., 2017)
Pellet
India, Punnapara Kerala Anchovy N.A. N.A. N.A. (Kripa et al., 2014)
Indonesia, Makassar Mackerel, Sprat, Spinefoot 0.3–1.1 Fragment, Fiber, PE, PP, PS, PET, (Rochman et al., 2015)
Film Nylon
Iran, Persian Gulf Scad 0.8 Fragment, Fiber, N.A. (Akhbarizadeh et al., 2018)
Pellet
Japan, Tokyo Bay Anchovy 2.3 Fragment, Fiber, PE, PP, PS (Tanaka and Takada, 2016)
Foam
Malaysia, Markets Anchovy, Croaker, Mullet, 1–14 Fragment, Fiber, PE, PP, PS, PET, (Karami et al., 2017a)
etc Film Nylon
Europe (fishes)
France, Mediterranean Sea Anchovy, Philchard, N.A. N.A PE, PS (Collard et al., 2017)
Herring
Greece, Aegean Sea Barracuda, Mackerel, Bogue 42, 28, 15.4 Fiber N.A. (Miliou et al., 2016)
German, North Sea Dab 0.03–0.19 Fiber, Fragment PE, PA, PP, PS, PET, (Rummel et al., 2016)
PU
Netherlands, North Sea Sprat 2 Sphere PMMA (Hermsen et al., 2017)
Portugal, Atlantic Coast Shad, Meagre, Mullet, etc. 0.09–1.66 Particle, Fiber PE, PA, PP, PL, Nylon (Neves et al., 2015)
Spain, Atlantic/ Mullet 1.9 Fiber, Fragment, N.A. (Bellas et al., 2016)
Mediterranean Sphere
Spain, Balearic Islands Bogue 2.47–4.89 Fiber N.A. (Nadal et al., 2016)
Spain, Mallorca Islands Mullet 0.32–0.68 Fiber PET, PS, PMMA, CA (Alomar et al., 2016)
Spain, Mediterranean Bogue, Anchovy, Philchard 1.18–1.46 Fiber N.A. (Ferreira et al., 2016)
Sweden, Coast Herring 0–53 Fiber N.A. (Ogonowski et al., 2017)
The U.K., Thames Flounder 0.2–0.85 Fiber PA, PE, PET, Nylon (McGoran et al., 2017)
Turkey, Mediterranean Mullet, Seabream, Meagre, 1–9.4 Fiber PA, PE, PP, PS (Güven et al., 2017)
etc
North America (fishes)
Canada, Eastern coast Cod 1–2 Fragment N.A. (Liboiron et al., 2016)
The U.S.A, California Anchovy, Bass, Salmon, etc 0.1–1.6 Fiber, Film, Foam N.A. (Rochman et al., 2015)
South America (fishes)
Argentina, Plata Estuary Pati 0.7–18.5 Fiber, Others N.A. (Pazos et al., 2017)
Brazil, Mamanguape Anchovy, Herring, 0.02–0.97 Fiber N.A. (Vendel et al., 2017)
Estuary Silverside, etc.
Brazil, Goiana Estuary Weakfish 0.08–0.52 Fiber (Dantas et al., 2012; Ferreira et al.,
2016)
Chile, Rapa Nui Cad, Snapper 2.5 Fiber, Film, N.A. (Phillips and Bonner, 2015)
Fragment
a: The data units defaulted to “items⋅animal-1”, other units were also used and specified in some cells due to the differences in identification methods or sample
quantification b: CP: cellophane, PA: polyamide, PAN: polyacrylonitrile, PE: polyethylene, PET: polyethylene terephthalate, PL: polyester, PMMA: poly
methylmethacrulate, PP: polypropylene, PS: polystyrene, PU: polyurethane; N.A. = Not Applicable
4
Fig. 2. Occurrence of MPs in salts and water around the world. The bars show the abundance of MPs detected in the salts and water. Their colors annotate the origins
of the salts or water: yellow, orange, and red represent sea salts, lake salts, and rock salts, respectively, while light blue, indigo blue, and dark blue indicate bottled
water, tap water, and effluents of drinking water treatment plants (DWTP), respectively. The inserts show the zooms of salts (left insert) and water (right insert) MPs
detected in Europe. The length of the bars indicates abundance in the logarithmic scale (legend on bottom-middle). The map depicts the highest MP levels detected in
36 countries. Data sources are described in SI Appendix, Table S1.
salt-equivalent intake is 10.06 g⋅d-1 (Dris et al., 2015). Based on the other studies extract MPs with the size limitation above the 0.22 µm or
median quantity of 506 items⋅kg-1 in salts, people may consume around even 1.5 µm (Mason et al., 2018; Schymanski et al., 2018); Second, the
2000 items at an average of MPs per capita per year (Fig. 1). Considering scanning electronic microscopy used in Zuccarello et al. (2019) contains
that MP items might be overlooked by current techniques, Lee et al. the higher resolution of 1 nm MPs but with smaller detection scale of
(2021) fit a computational model to infer the number of MPs missed in 1 mm2, whereas the detection limit of MPs in other studies is above 1 or
the previous reports and corrected the estimation of yearly MPs intake 5 µm by the μ-Raman or μ-FTIR, respectively (Mason et al., 2018;
per capita to ~1.9 × 104 items (Fig. 1). Schymanski et al., 2018). Therefore, a unified method for extracting and
detecting MPs is urgent for better comparing their occurrence in the
2.1.3. Ingestion via drinking water environment matrix.
Microplastic pollution has been widely found in effluents from With an average daily consumption of 1.4 L of water for an adult, it
drinking water treatment plants (DWTPs), plastic bottled water, and tap could be estimated that the ingested MPs of an individual through
water from over twenty different countries (e.g., Germany, Czech, Nor drinking water reached 3.1 × 105 (average: 4.7 × 103) items per year
way, China, UK, Italy, USA, Denmark, Indonesia, etc.) (Fig. 1 & 2 and (Fig. 1 & 2). If considering that the daily water consumption consists of
Table S1). Traditional technologies for drinking water treatment can 83% tap and 17% bottled water, the annual intake of MPs per capita
achieve a removal rate of up to 90 % for plastic particles (Pivokonsky could reach as high as several billion, mainly from the highly contami
et al., 2018). However, the treated water still contains hundreds of MPs nated plastic bottled water (4.69 × 109 items⋅year-1, as compared to
per liter, which might be used for drinking. The MP contents in both raw 3.9 × 103⋅year-1 items from tap water). Such a high estimation was
and treated water varied greatly. In a comparison of two DWTPs from calculated based on the worst-case scenario from the investigations in
Czech, the results revealed that DWTPs (Milence) had 23 ± 2 and 14 ± 1 Italy, which did not specify the sample preparation and detection pro
items⋅L-1 in its raw and treated water, while these numbers of DWTP cesses in detail (Zuccarello et al., 2019). The annual intake could drop to
(Plzen) were 1296 ± 35 and 151 ± 4 items⋅L-1, respectively (Pivokonský 4.1 × 104 items if based on the median value of MPs in (plastic) bottled
et al., 2020). The traditional water treatments were not designed for water in Table S1. In addition to the water, some beverages preferred by
MPs. These measures may help remove the MP contaminants at a higher some children contain a large number of MPs (Liebezeit and Liebezeit,
concentration but cannot clear them all. 2014). The children’s daily intake of MPs through this way is over
Besides, individuals could also drink MPs through tap and bottled 87.8 μg⋅kg-1 (3.3 × 106 items⋅kg-1) in the worst-case scenario (Zuccar
water. Kosuth et al. (2018) investigate the presence of MPs larger than ello et al., 2019). For adults, the annual amounts of beer consumed by
100 µm in 159 samples of globally sourced tap water and discovered the adult men and women were estimated at 13.6 and 4.9 L, respectively. As
scale ranging from 0 to 61 items⋅L-1 (with an overall mean of 5.45 a large scale of MPs ranged from 2 to 79 fibers⋅L-1, 12–109 fragments⋅L-1
items⋅L-1). Similarly in the case of bottled water, reported MP contam and 2–66 granules⋅L-1 reported from beers, the intake of MPs each year
ination in various studies mainly fulled between 10 and 103 items⋅L-1 changed considerably with the ranges of 217.6–3454.4 items for male
(Fig. 1 & 2 and Table S1). A very high abundance of MPs in the worst and 78.4–1244.6 items for female.
scenarios has been found in Italy (5.4 ×107 items⋅L-1) within 0.5–10 µm
in size (Zuccarello et al., 2019). Such a huge discrepancy generated 2.1.4. Ingestion via plastic packages
might be attributed to many issues, especially the extraction and Food containers, directly in contact with food, nowadays are also
detection methods (Table S1). In detail, Zuccarello et al. (2019) considered as an unintentional source for MPs entering the human be
extracted the MPs within 10 µm by evaporation after digestion (3 mL 65 ings (Du et al., 2020; Hernandez et al., 2019; D. Li et al., 2020). (Li et al.,
% HNO3) and removal (3 mL ultrapure water and 9 mL CH2Cl2) of 2020a) investigated 48 countries (or regions) and evaluated around
organic matters, while the traditional method (e.g., filtration) used by 1.5 × 106 items⋅d-1 MPs released from feeding bottles affected by the
5
sterilization, periodic fluctuations and water temperature. The high density, modernization, and sampling site. Generally, developing
temperature could also enhance the MPs release from the plastic cups countries with a more dense population (Shanghai: 24.18 million;
(Ranjan et al., 2021) and teabags (Hernandez et al., 2019). In 15 min, Tehran Metropolis: 8.2 million) produce more domestic wastes than
the hot water (85–90 ◦ C, 100 mL) could result in 2.5 × 104 items of MPs Hamburg (1.84 million) (Dris et al., 2015; Liu et al., 2019). In remote
and (102.3 ± 21.1)× 106 items of sub-MPs released from paper cups areas with sparse populations, the average abundance of atmospheric
(Ranjan et al., 2021), while higher temperature (≥ 90 ◦ C) could release MPs can be two orders of magnitude lower. However, Yantai has a
~1.16 × 1010 items of MPs and 3.1 × 109 items of NPs from one tea bag smaller population (2.61 million) but much higher MP items than
into the cup (Hernandez et al., 2019). Due to the unclear rate of recur Dongguan (7.45 million) due to their geographical difference. Yantai is a
rence, the annual intake via these ways is still limited. Only one report coastal city that accepts higher MP deposition from the water vapor
estimated the annual MP intake achieving to ~2977 items⋅person-1 exchange (Ivar Do Sul and Costa, 2014). The distribution of MPs is also
through take-out food, and the data could increase to 1.06 × 105 items if attributed to the wind direction and deposition height. In horizontal
people consume plastic-packaged food 4–7 times weekly (Du et al., transportation, the average concentrations of airborne MPs increase at
2020) (Fig. 1). downwind sites (Browne et al., 2010). The atmosphere can quickly
convey the MPs to remote and sparse areas over 95 km (Allen et al.,
2.1.5. Ingestion via other food items 2019). Vertically, Liu et al. (2019) recorded that the highest concen
Other food items could also transport MPs into the human beings trations were at 1.7 m above the ground, decreasing as altitude
(Liebezeit and Liebezeit, 2014; Oliveri Conti et al., 2020). Recently, increased.
many publications have reported that the MPs can penetrate the roots of With the MP concentrations of 1.1–59.4 fibers⋅m-3, the contamina
various plants/vegetables, including Arabidopsis thaliana (Sun et al., tion of MPs in indoor environments (e.g., offices, homes, and dormi
2020; Taylor et al., 2020), wheat Li et al., (2020b); Lian et al., 2020; tories) is more serious than in outdoor environments (0.3–1.5 fibers⋅m-3)
Taylor et al., 2020), carrot (Dong et al., 2021), lettuce (Li et al., 2020b) (Zhang et al., 2020a,b). MP fallout was also reported in students’ dor
and rice seedlings (Liu et al., 2022). Then the MPs could be further mitories, offices, and corridors. The highest average microplastic
translocated upwards to shoots or even leaves under the transpiration abundance (9.9 × 103 items⋅m-2⋅d-1) were found in the dormitory, fol
pull (Li et al., (2020b); Lian et al., 2020; Liu et al., 2022). Moreover, lowed by 1.8 × 103 items⋅m-2⋅d-1 in the office and 1.5 × 103 item
little study has been reported on the occurrence of the plants in the s⋅m-2⋅d-1 in the corridor (Zhang et al., 2020b). The temporal distribution
environments because of the insufficient detection limits. A survey of MPs in different locations is deferred between weekdays and week
estimated that the higher median levels of MPs (1.51–2.52 µm) ranged ends. In the office, the number of MP items on the weekdays (2.4 × 103
from 5.2 × 104 items⋅g-1 lettuce to 2.23 × 105 items⋅g-1 of apple, which items⋅m-2⋅d-1) was around double that amount on weekends (1.2 × 103
may result in 4.62 × 105 and 1.41 × 106 items of MPs (1.51–2.52 µm) items⋅m-2⋅d-1). In the dormitory, on the other hand, the average con
entering the bodies of adults and children, respectively (Oliveri Conti centration of MPs on weekends (1.4 × 104 items⋅m-2⋅d-1) was approxi
et al., 2020). Additionally, a terrestrial trophic transfer among the soil mately three-fold of that on weekdays (5.8 × 103 items⋅m-2⋅d-1) (Zhang
(0.87 ± 1.9 items⋅g− 1), earthworms (14.8 ± 1.9 items⋅g− 1), and et al., 2020b). Human activities are frequent in the office on weekdays
chickens (129.8 ± 82.3 items⋅g− 1) (Lwanga et al., 2017). However, it is and in the dormitory on weekends. This phenomenon indicates that
hard to obtain the accurate MP intake from only this publication. human activities should be blamed for the abundance of MPs. One of the
Therefore, more publications on trophic transfer for MPs entering the most typical activities in indoor environments is the influence of air
human beings are urgent for evaluating human intake accurately. conditioners. The use of air conditioners can disrupt the stable airflow,
MPs in other daily foods have also been reported. Sugars contained causing the resuspension of MPs in the room space. Walking and shut
217 ± 123 items⋅kg-1 of fiber and 32 ± 7 items⋅kg-1 of fragments, and a ting doors might also interfere with the airflow in indoor areas. Another
kilogram of honey had 166 ± 147 fibers and 9 ± 9 fragments on average study further determined the MPs in different indoor environments (Zhu
(Liebezeit and Liebezeit, 2013). Based on that average American people et al., 2022). In contrast to the classroom, the residential apartments
consume 0.73 kg of honey every year, it is estimated that 90.87–270.21 showed about 4 times higher, with fiber being the dominant shape and
(average: 181.04) items of MPs may enter the human body. This amount polyester as the main type (Zhu et al., 2022). These results also sug
is still notable, although the intake of honey contributed substantially gested the contribution of human activities on MPs abundance in indoor
less. For many other daily food items (e.g., beef, pork, etc.), the environments as washing or wearing could easily release the fibers from
contamination levels and actual consumed amounts remain largely un clothes and textiles.
known. Therefore, investigations on MP in daily food could be helpful in The MP intake via human inhalation has been estimated in many
comprehensively assessing the global human exposure to MPs through studies (Fig. 1). For example, Nematollahi et al. (2022) demonstrated
the diet. that the mean estimated daily intake (EDI) of MPs ranges between 0.6
items⋅kg-1 for adults and 13.7 items⋅kg-1 for infants, respectively. For the
2.2. Inhalation of MPs in the air students, the annual intake of MPs in the study is located at the scale of
219–5000 items⋅kg-1, with a higher exposure risk for elementary school
Another critical route for MPs entering the human body has been students (~1773.9 items⋅kg-1) than middle and high school students
identified as the airborne route. As described in Table 2, it was first (~730 items⋅kg-1). For university students, the exposure risk decreases
recorded in the atmosphere near the center of Paris (France) with an significantly with about 100 items⋅kg-1 annually (Zhu et al., 2022). This
average daily fallout of 118 items⋅m-2⋅d-1 of MPs (from 29 to 280 discrepancy is mainly due to the children’s lower weight and higher
items⋅m-2⋅d-1) (Dris et al., 2015). In Hamburger (German), a comparable ingestion rate. The adults are often exposed to MPs in the office with
abundance of MPs (~275 items⋅m-2) was detected in daily atmospheric their EDI ranging from about 0.32–0.6 items⋅kg-1 bodyweight⋅day -1 (Liu
fallout over 12 weeks (Klein and Fischer, 2019). In contrast to the et al., 2019; Zhu et al., 2022). According to the average weight of males
developed countries, higher levels of airborne MPs are reported in (90.62 kg) and females (77.47 kg) (Fryar et al., 2018), the annual intake
developing countries. In China, an MP abundance of 175–313 item of MPs could be estimated at (1.05–1.97) × 104 items for males and
s⋅m-2⋅d-1, 115–602 items⋅m-2⋅d-1, and ≤ 4.18 items⋅m-3 of MPs was (0.91–1.70) × 104 items for females (Liu et al., 2019; Zhu et al., 2022). A
recorded in three cities Dongguan, Yantai, and Shanghai, respectively comparable annual intake was also reported ranging around (3.5–7.9)×
(Cai et al., 2017; Liu et al., 2019). In Iran, about 0.3–1.1 items⋅m-3 were 104 or (0.9–4.74)× 104 items for males and females, respectively (Cox
found in Asaluyeh County, while ~0.29–2.02 items⋅kg-1 were detected et al., 2019; Zhang et al., 2020a). These exposure levels of the inhaled
in the street duct of Tehran Metropolis (Dehghani et al., 2017). The MPs are mainly built on the identification of stereomicroscope,
varying concentrations of MPs in cities mainly depend on the population micro-Fourier Transform Infrared Spectroscopy (μ-FTIR), and μ-Raman,
6
Table 2
Occurrence of microplastics in possible atmospheric depositionsa.
Locations Size (μm) Abundance Shapes Extraction Identification References
(items⋅m-2⋅d-1)b
Atmospheric fallout
Dongguan, China 200–700 175–313 Fiber: 80%; Filtration (φ1.0 µm) Microscopy, (Cai et al., 2017)
Foam and film μ-FTIR
Ho Chi Minh City, 300–5000 71–917 Fragment; Fiber Filtration (φ1.6 µm) Microscopy (Dris et al., 2015)
Vietnam
Paris, France 100–5000 29–280; mean:118 Fiber: > 90% Filtration (φ1.6 µm) Microscopy (Dris et al., 2015)
Fragment: ~10%
Paris, France 50–500: 3%; 2.1–355.4 Fiber Filtration (φ1.6 µm) Microscopy (Dris et al., 2015)
200–600:
42%;
600–1400:
~40%
Atmospheric deposition
Guangzhou, China 50–5000 51–178 Fibers, fragments, films Filtration (φ0.45 µm) Microscopy, (Huang et al., 2021a)
and microbeads μ-FTIR
Hamburg, Germany < 63: ~60%; 275 (Range Fragment: 90% Staining (Nile Red) Microscopy, (Klein and Fischer,
63–300: 136–512) Fiber:10% μ-Raman 2019)
~30%;
> 300: ~20%
Pyrenees moutains, 100–300 Fragment: 249; Fragment: 68%; Film: Filtration (φ0.45 µm) Microscopy, (Allen et al., 2019)
Europe Film: 73; ~20%; Fiber:12% μ-Raman
Fiber: 44
Yantai, China 23–500: Fiber: 115–602; Fiber: 95%; Filtration (φ1.0 µm) Microscopy, (Cai et al., 2017)
> 50% Others: 40 Film and foam μ-FTIR
Suspended atmospheric microplastics
Shanghai, China 23–500: 0 ~ 4.18 items⋅m-3 Fiber: 67% Fragment: Filtration (φ1.6 µm) Microscopy, (Liu et al., 2019)
> 50% 30% μ-FTIR
Dust (including urban and rural dust)
House dust, Australia 200–400 22–6169 Fiber Filtration (φ0.6 µm) Microscopy, (Soltani et al., 2021)
μ-FTIR
House dust, China – PC: 18; PET:9200 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
House dust, Colombia – PC: 11; PET:3900 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
House dust, Greece – PC: 34; PET:15000 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
House dust, India – PC: 20; PET:2000 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
House dust, Japan – PC: 63; PET:20000 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
House dust, Kuwait – PC: 6.9; PET:10000 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
House dust, Pakistan – PC: 6; PET:4400 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
House dust, Romania – PC:15; PET:14000 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
House dust, Saudi – PC: 58; PET:20000 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
Arabia
House dust, South Korea – PC: 54; PET:27000 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
House dust, the USA – 87–14000 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
House dust, Vietnam – 120–11000 – Heat digestion LC-MS/MS (Zhang et al., 2020c)
Shiraz, Iran 50–5000 5463.5 items⋅g-1 Fiber, Fragment, Sheet Staining (Fluorescent Fluorescence (Nematollahi et al.,
pigments), Filtration microscopy, 2022)
(φ2.0 µm)
Tehran metropolis, Iran 250–500 (0.29–2.02) × 104 Granule: 60%; Fiber: Staining, Filtration (φ2.0 µm) Fluorescence (Dehghani et al., 2017)
items⋅kg-1 35%; Sphere: 5% microscopy,
Outdoor
Paris, France 50–450 0.3–1.5 items⋅m-3 Fiber Filtration (φ1.6 µm) Microscopy (Dris et al., 2015; Q.
Zhang et al., 2020b)
Plymouth, UK 0–10000 952 items Fragment:65% Filtration (φ280 μm) FTIR (Browne et al., 2010)
Indoor
Paris, France 50–450 1.1–59.4 Fiber Filtration (φ1.6 µm) Microscopy, (Dris, 2017)
items⋅m− 3 μ-FTIR,
μ-Raman
Office, Shanghai China 50–2000: 1.8 × 103 Fiber Filtration (φ5 μm) Microscopy, (Zhang et al., 2020b)
80% μ-FTIR
3
Dormitory, China 50–2000: 9.9 × 10 Fiber Filtration (φ5 μm) Microscopy, (Zhang et al., 2020b)
80% μ-FTIR
Residential apartment, 200–1000 150–3861 items⋅g-1 Fiber (80%) Filtration (φ2 μm) Microscopy, (Zhu et al., 2022)
Hangzhou, China μ-FTIR
Hotels, Hangzhou, 200–1000 74–2065 items⋅g-1 Fiber (87%) Filtration (φ2 μm) Microscopy, (Zhu et al., 2022)
China μ-FTIR
-1
Offices, Hangzhou, 200–1000 112–1470 items⋅g Fiber (92%) Filtration (φ2 μm) Microscopy, (Zhu et al., 2022)
China μ-FTIR
Dormitory, Hangzhou, 200–1000 99–1166 items⋅g-1 Fiber (80%) Filtration (φ2 μm) Microscopy, (Zhu et al., 2022)
China μ-FTIR
Classroom, Hangzhou, 200–1000 62–434 items⋅g-1 Fiber (88%) Filtration (φ2 μm) Microscopy, (Zhu et al., 2022)
China μ-FTIR
a: Represent data summarized in the context, more survey reports on MP pollution in the air are summarized in Table S2 of the Supplementary Information. b: The data
units were defaulted to “items⋅m-2⋅d-1”, other units were also used and specified in some cells due to the differences in identification methods or sample quantification.
7
expressed in a unit of items per year. Once using the mass spectrometry, risks when the additives interact and then cause synergistic or antago
ng⋅kg-1 is the widely used unit. Therefore, a study estimated the EDI of nistic effects on human beings. These included energy homeostasis
polyethene terephthalate (PET) and polycarbonate (PC) on the scale of disruption, circulatory system disorder, immune system dysregulation,
3.6 × 102-1.5 × 105 and 0.88–2.7 × 102 ng⋅kg-1 bodyweight⋅day-1 neurological dysfunction, etc (Lu et al., 2018).
(Zhang et al., 2020b). Since the conversion of the two units has not been
established, it is still hard to link the mass concentrations of MPs and 3. Distribution of MPs in the human body
their abundance. Meanwhile, the MPs are high heterogeneity with
different sizes, shapes and surface charges (Jeong et al., 2016), the Once entering the human body through ingestion, inhalation, and
physicochemical properties should also be considered in future studies dermal contacts, understanding the distributions of MPs is the utmost
to increase the accuracy of intake calculations. priority in exploring their potentially detrimental effects (Gouin et al.,
2022). The ingested MPs directly pass through the oesophagus and into
2.3. MP exposure through dermal contact the stomach, digested in about 2–6 h (Fig. 3) (Dawson et al., 2018). After
that, the insoluble MPs with a size smaller than 1.09 µm can penetrate
Dermal contact is another known way to be exposed to MPs, the gut epithelium and enter the circulatory system. In contrast, some
although it seems less prevalent than ingestion and inhalation. MPs’ larger MPs are transported to the midgut and hindgut. MPs with a size up
dermal exposure often occurs when cleaning the body (e.g., toothpaste, to 130 µm can translocate into human tissues via paracellular transport
scrubs) and wearing clothing. Due to the skin pores ranging from 40 to in the form of desorption (Cox et al., 2019). Unlike ingested MPs,
80 µm, the dermal barrier could be crossed by NPs (<100 nm), synthetic airborne MPs are likely to deposit in the human lungs’ alveolar regions
fibers (<25 µm), the monomers, as well as the additives (Wu et al., and then translocate into epithelial layers through the gas exchange
2022). Because of the sample biosecurity, method limitations, and between the alveoli and capillaries (Barlow et al., 2017). For example,
ethical constraints, no human intake of MPs via this pathway has been Jenner et al. (2022) found an average of 1.42 ± 1.50 items⋅g− 1 of MPs
documented in publications. However, some typical plastic additives, occurred in the human lung tissues, and males contain higher levels
including brominated flame retardants (BFRs), bisphenols (BPs), tri (2.09 ± 1.54 items⋅g− 1) than females (0.36 ± 0.50 items⋅g− 1). This
closan (TCS), and phthalates, are investigated, which might be absorbed phenomenon might be attributed to the smaller airways in females
during the dermal exposure of MPs. (Jenner et al., 2022). Among these MPs, almost half (49%) were iden
Dermal absorption of plastic additives were 76.9–101 ng⋅kg−bw1d− 1 tified as a shape of fibers by μ-FTIR. MPs with a higher
(BFRs), 12.1 ng⋅kg−bw1d− 1 (BPs), 1.20 × 10− 2 ng⋅kg−bw1d− 1 (TCS), length-to-diameter ratio may finally enter the cardiovascular system.
78 μg⋅kg−bw1d− 1 (Diethyl phthalate; DEP), 0.82 μg⋅kg−bw1d− 1 (di(2-ethyl Most larger MPs (> 0.2 µm) in the bloodstream might be removed into
hexyl)phthalate; DEHP), 0.36 μg⋅kg−bw1d− 1 (Di-n-butyl phthalate; DnBP), the intestine through splenic filtration (Rist et al., 2018). Still, some
and 0.03 μg⋅kg−bw1d− 1 (Dimethyl phthalate; DMP) (Abdallah and Harrad, smaller NPs (< 0.1 µm) were hypothesized to stay in the blood. This
2018; Koniecki et al., 2011). The absorption levels of these contaminants phenomenon was also certified by a recent study that recorded the mean
are mainly affected by the contacting amount, time, additives concen concentration of plastic particles in blood was 1.6 µg⋅mL− 1 detected by
tration, and physiochemistry, respectively. A significant (P < 0.05) gas chromatograph-mass spectrometry (Leslie et al., 2022). In a
negative correlation is observed between the octanol-water partition nano-scale, the mass of one NP item is evaluated to be ~0.8–1.4 ng,
coefficient (log Kow) and the absorbed fractions of the plastic additives. therefore, it could be calculated that (1− 2) × 103 items⋅mL− 1 of NPs
It seems difficult for more lipophilic contaminants to penetrate the hy contained in human blood (Sobhani et al., 2020). These NPs could flow
drophilic epidermis (Abdallah and Harrad, 2018). There are potential into and accumulate in all organs, including the liver and kidney
Fig. 3. Pathways and potential risks of MPs entering into the human body. Three main routes for MPs entering into the human body: ingestion, inhalation and dermal
contact. In ingestion way, MPs direct go through the oesophagus into the stomach. Some MPs (<1.09 µm) penetrate across the gut epithelium and enter the blood
circulatory system, whilst some larger MPs are transported to the mid and hindgut. The airborne MPs are likely to deposit in alveolar regions, and then translocate
into epithelial layers through the gas exchange. Thereafter, the larger MPs (> 0.2 µm) are removed from the lymph into the intestine, while some smaller NPs (<
0.1 µm) in the blood flow into and accumulate in all organs. In contrast to the ingestion and inhalation, dermal contact seems less prevalent due to that the skin pores
(40–80 µm) are small enough for only some NPs, synthetic fiber, and monomers to penetrate. Once they are distributed in each organ, they could trigger several toxic
effects, including oxidative stress, inflammation, immune dysregulation and neurological dysfunction.
8
(Vethaak and Legler, 2021). Up to date, no direct evidence supported inflammation, immune responses and neurological dysfunctions, and
that NPs could cross the blood-brain barrier, while large numbers of contribute to the pathogenesis of the chronic disease.
publications displayed that nanoparticles (10–250 nm) could penetrate
the barrier and be retained in the brain (Gregory et al., 2020; McCright 4.1.1.1. In vitro. A variety of cell lines were used to assess the harmful
et al., 2022). The dissimilarity in physicochemical characteristics of effects of different exposure pathways (e.g., ingestion, air inhalation, and
particles, such as size, chemical activity, and their chemical composi dermal contact), which can serve the purpose of an early warning sys
tions, has been linked to the difference in their toxicity for years (Luyts tem. Oxidative stress that was induced by various types of MPs in
et al., 2013). Size-dependent effects of particles have been verified as the different cell lines has been documented, as seen in Table 3 and Table S3.
fact that the smaller particles with more inert character could have a In general, the MP challenges increased the cellular ROS. Once they
higher concentration in the brain. With the similar physicochemical enter cells, MPs may damage organelles including mitochondria,
characteristic (e.g., inert, nano-sized), it has been extrapolated based on causing instability in mitochondrial membrane potential and production
the results from the nanoparticles of chemically inert materials, such as of cellular ROS (Seaver and Imlay, 2004; Wang et al., 2021). To
gold (Au) and titanium dioxide (TiO2), that NPs might have the potential neutralize infectious foreign particles, the innate immune defense
to enter and harm the brain (Prüst et al., 2020). Apart from these, the mechanisms would activate enzymes such as NADPH-oxidase, gener
characteristics different between NP and other nanoparticles may also ating superoxide and hydrogen peroxide (Yang et al., 2013). It has also
have their roles. The composition of nanoparticles, for example, de been suggested that free radicals absorbed onto MPs, particularly onto
termines the surface chemistry, thereby influencing the aggregation, secondary MPs (e.g., aged MPs), contribute to the ROS caused by MP
dissolution, and interaction with other molecules (Kim et al., 2020; exposure (Pannetier et al., 2019). However, it is still difficult to establish
Luyts et al., 2013; Zhao et al., 2021a). Although the knowledge gained a quantitative link between MP exposure and ROS generation based on
from nanotoxicological studies could be extended to speculate on the the available data, some of which seem controversial and need further
potential of NPs to cross the blood-brain barrier, more direct evidence is investigation. For instance, Liu et al. (2018) reported a dose-dependent
still needed. increase in ROS in Huh7 (a liver cell line) challenged with polystyrene
(PS) MPs (100–200 μg⋅mL-1), but not at a lower concentration
4. Metabolism along with the potential toxicity of MPs (50 μg⋅mL-1). Schirinzi et al. (2017) examined a much lower concen
tration range (0.01–10 μg⋅mL-1) and also observed that only 10 μg⋅mL-1
Plastics are chemically inert, and there has been no evidence of of PS caused dramatic ROS elevation in the human cerebral cell T98G.
biodegradation inside the human body to date. Although our body does PE MPs, on the other hand, induced ROS in T98G cells only at lower
not metabolize the MP particles, the impacts of MPs on the metabolism levels (0.05–0.1 μg⋅mL-1). Besides the diversities in MP type, particle
have long been documented. Also, MPs function as carriers for a variety size and shape, and cell lines, there were variabilities in experimental
of toxic compounds, some of which can be metabolized and caused procedures among studies. The effects of these differences are worthy of
additional harm. The absorbed MPs cause various biological effects in further studies to clarify the MP toxicity. Moreover, many studies have
various organs (Rist et al., 2018). Epidemiological investigations have shown that MP-induced oxidative stress is age- and size-dependent. This
reported the prevalence of interstitial lung disease among workers from phenomenon was explained by the increased particle toxicity (e.g.,
the polymer factories in the Netherlands (Kremer et al., 1994). Similarly, physical damage) of the aged or smaller MPs and/or their enhanced
the employees in nylon flock plants have more work-related symptoms absorption of free radicals. The contributions of various mechanisms are
(according to a histopathological analysis) in Canada and the USA unknown.
(Eschenbacher et al., 2008). Recent evidence also certified that the
ingested MPs have a significant positive correlation with the severity of 4.1.1.2. In vivo. In addition to cell lines, the toxic effects of MPs on
inflammatory bowel disease (IBD) (Yan et al., 2021). In detail, a higher living organisms have been widely reported. It has been observed that
concentration of the fecal MPs was found in IBD patients (41.8 items/g PS microbeads (5 nm) significantly increased ROS levels, which subse
dm) than in healthy people (28.0 items/g dm) (Yan et al., 2021). quently enhanced various activities in fish: SOD, GSH-Px, glutathione
Epidemiological studies can provide direct and relevant evidence for the reductase (GR), and glutathione S-transferase (GST). A marine fish
association between MP exposure and potential hazards/diseases. (Sebastes schlegelii) treatment with PS significantly promoted ROS pro
Meanwhile, the epidemiological study could prevent diseases from duction (Yin et al., 2019). MPs with other chemical compositions (PE,
occurring in the population, promote people’s health, and prolong PP, and PVC) have been found to induce a similar intestinal impairment
human life. in the zebrafish (Danio rerio) by increasing the GST expression (Lu et al.,
However, these studies on the health risks of MPs are still in their 2016). The acute inflammation was stimulated by PP exposure, which
infancy, and the toxic mechanism of MPs is largely unclear. Thus, can generate many free radicals and then help trigger the degradation,
increasing metabolic investigations are conducted continuously to cracking, and additive leaching from the polymer structures. Aside from
reveal the biological interactions of MPs in vitro and in vivo. Lacking the acute toxicity, chronic exposure to MPs (20 µm at 1 mg⋅L-1) in
direct evidence from humans, this section combined the in vitro results mammals could also result in significant SOD increases. PS-MPs accu
from human cells with in vivo data from vertebrates to sketch the role of mulated in the kidneys of the mice treated by oral gavage, giving rise to
MPs in human metabolism as well as their potential toxicity. more histopathological lesions, higher levels of ER stress, markers of
inflammation, and autophagy-related proteins after the 4 weeks of
4.1. Toxicity originated from MPs exposure (Deng et al., 2017). Although the generated ROS levels could
increase plasma glucose in the mouse liver, the oral administration of PS
4.1.1. Oxidative stress NPs (80–157.5 nm) did not influence insulin secretion levels during the
Oxidative stress, which is generally characterized by the generation whole exposure period (0–120 min) in mice (Fan et al., 2022).
of reactive oxygen species (ROS), could influence the growth and
development of specific human cell lines, and alter the community 4.1.2. Inflammation
structure and function of the microbiome. Meanwhile, the disturbance Inflammation is part of the body’s complex biochemical reaction to
of other oxidative stress-related antioxidants (e.g., superoxide dismutase harmful stimuli, including MPs. Inflammation is thought to be a pro
(SOD), catalase (CAT), glutathione peroxidase (GSH-Px)) has been tective mechanism that helps to remove the source of cell harm and
observed in the liver, kidney, and gut of mice after MPs exposure, as commence tissue healing. Inflammation is mainly affected by the
represented by the imbalance of energy and lipid metabolism. As the physicochemical nature of MPs and their concentrations in the bodies.
most prominent biomarker issue, oxidative stress can further trigger
9
Table 3
Toxic effects of microplastics on fish, mice and human cellsa.
Types of Partical size (μm) Shape Concentration Exposure Time Target Potential human risks References
MPs (μg⋅mL-1) (h)
Oxidative stress
PP ~20, 25–200 Fragment 1000 48 HDF cells Cell viability ↓b, (Hwang et al.,
ROS ↑c 2019)
PS 0.02–0.07 Fragment 2.5–300 12 A549 Apoptosis ↑ (Xu et al., 2019)
PS 0.1, 5 Sphere 20 24 Caco-2 cells Cell viability ↓, ROS ↑ (Wu et al., 2019)
PS 0.05 Sphere 0.04–1 24 and 48 Raji-B, TK6, Mild toxicity, ROS ↑ (Rubio et al., 2020)
THP-1
PS 5 Fragment 0–500 24 L02 cells ROS ↑, Hepatic apoptosis (Li et al., 2021)
PS 2 Sphere 75 5 min-3 days HK-2 cells ROS ↑, ER ↑ (Wang et al., 2021)
PS 0.5, 15 Sphere 1.9 × 105 24 Rockfish ROS ↑ (Yin et al., 2019)
PS 0.07, 0.5 Beads 0.02, 0.2, 2 24 Zebrafish Vacuolation ↑, Infiltration ↑, (Lu et al., 2016)
Necrosis ↑
PS 5, 20 Sphere 0.1 mg⋅d-1 1–28 days Mice ROS ↑, ER ↑ (Deng et al., 2017)
Inflammation
-2
PS 1.72–4.06 Sphere 1–1000 μg⋅cm 24, 48 BEAS-2B IL6↑, IL8↑ (Dong et al., 2020)
PS 0.025–0.07 Sphere 1.14, 25 24 A549 cells IL-6, IL-8, NF-κb, and TNF-α (Xu et al., 2019)
PS 15, 25 Bead, Fragment, 104 21 days Zebrafish IL1α ↑, 1β ↑, D-Lac ↑ (Qiao et al., 2019a)
Fiber
PS 5 Bead, Fragment, 5 × 104, 5 × 105 21 days Zebrafish ROS, Catalase↑ (Qiao et al., 2019b)
Fiber
PS 5 Sphere 105-106 6 weeks Mice IL1α ↑, IL1β↑, IFN↑ (Jin et al., 2019)
PS 0.5,50 Sphere 104-1010 5 weeks Mice IL1α, IL1β, IFN↑ (Lu et al., 2018)
Immunotoxicity
PS 0.5 Sphere 0–40000 4–48 Crab SOD, GSH, GSH-Px ↑ (Yu et al., 2018)
PS 100–400 Fragment 10 mg⋅d-1 28 days Rainbow trout Phagocytosis↓ (Ašmonaitė et al.,
2018)
PS 32–40 Sphere 0.1, 1 28 days Juvenile guppy TNF-α, IFN-γ, TLR4, IL6↑ (Huang et al.,
2020)
-3
PS, PC 1.007 (PS), 1.710 Sphere (0.025–0.2) × 10 2 Minnow Oxidative burst activity*d (Greven et al.,
(PC) 2010)
PS 0.05 Sphere 1, 5, 50 0.5, 1 Mussel Immune-related genes ↑; Lysosomal (Chen et al., 2021)
enzymes ↓
PS 0.5, 50 Sphere 1 5 weeks Mice Mucin 1↓ (Lu et al., 2018)
PS 0.5, 50 Sphere 105-106 6 weeks Mice Kruppel like factor 4↓ (Jin et al., 2019)
PS 1, 4, 10 Sphere 1.25–34 mg⋅kg-1 28 days Mice – (Stock et al., 2019)
Neurotoxicity
PS 0.055 Sphere 7.8–250 1–15 days Neural cells Internalization (Murali et al.,
2015)
PS 2 Sphere 8,16 mg⋅kg-1 8 weeks Mice IEGs ↓ (Lee et al., 2022)
MPs 1–5 Sphere 0.26–0.69 96 Seabass Neurotransmitter ↑ (Barboza et al.,
2018a)
MPs 1–5 Sphere 0.26–0.69 96 Seabass Brain AChE ↓ (Barboza et al.,
2018b)
4–6 -3
MPs 17.19 Fragments 4 × 10 items m 5 days Zebrafish AChE↑ (Guimaraes et al.,
2021)
a: Represent data summarized in the context, more survey reports on the toxic effect of MPs are provided in Table S3 of the Supplementary Information. b, c, d: the “↑”,
“↓” and “* ” mean the upregulation, downregulation and alteration of the corresponded parameters, respectively.
Inflammatory abnormalities encompass a broad range of conditions that hypothesized from the chemical and physical effects (Choi et al., 2020).
affect immune cells, blood vessels, and molecular mediators. At the same In the aspects of chemical effects, the impurities in MP synthesis are
time, the immune cells would be activated and release a variety of in released and induce inflammatory responses (Wu et al., 2020a). Given
flammatory factors (such as TNF- α, IL-6, IL-1β, etc.). the physical effects, MPs directly interact with fibroblasts and the red
blood cells, inducing hemoglobin and lactose dehydrogenase release
4.1.2.1. In vitro. Recent studies confirmed that the inflammatory cy because of the hemolysis and cell membrane damage (Choi et al., 2020).
tokines were induced by MPs in various cell lines, including human Once the amplification occurred, the MP-induced local inflammatory
epithelial cells (e.g., BEAS-2B, A549, AGS cells) (Dong et al., 2020; Shi response can lead to further systemic inflammation and contribute to
et al., 2021; Xu et al., 2019). Inflammation is the primary reflection of COPD and asthma.
the damage of alveolar BEAS-2B cells by that the expression of the
Interleukin (IL)− 6 and IL-8 were both significantly augmented (Dong 4.1.2.2. In vivo. In addition to the cell lines, the inflammatory re
et al., 2020). Another study utilized the qPCR analysis finding the sponses were quietly reported in the organisms, especially the fishes and
up-regulating of the pro-inflammatory cytokines (IL-6, IL-8, Tumor mice. Qiao et al., (2019a) tested the influences and possible toxicity of
Necrosis Factor (TNF) α), which further destroyed the integrity of A549 MPs (bead, fragment, and fiber; 15–25 µm) in zebrafish after 24 h and
cells membranes, resulting in the cell necrosis (Xu et al., 2019). How 21 days of exposure. They then induced the alterations of specific bac
ever, some studies demonstrated that MP exposure was not efficient in teria (reduction of relative abundance of Aeromonas and Pseudomonas)
causing inflammation. In human Caco-2 cells, larger MPs (4 and 10 µm) and an increase in IL 1α, resulting in the dysbiosis of gut microbiota and
did not trigger the inflammation at any concentration, while the inflammation. Similar to that, the gut microbes of zebrafish were
small-sized MPs (1 µm) could cause inflammation at very high levels significantly changed in the groups treated with MPs (0.5, 50 µm) with
(108 items⋅mL-1) (Stock et al., 2019). the phenomenon of Proteobacteria and Bacteroidetes decrease and Fir
This inflammatory response in the cell lines was further micutes and Fusobateria increase (Lu et al., 2018). Low inflammation was
10
found in the zebrafish gut as the up-regulation of IL1α, IL1β, Interferon γ There is an urgent need to further comprehend the potential MP impacts
(IFN γ), and protein levels of interleukins by exposing 5 µm PS MPs (Jin on human immune systems.
et al., 2019). The inflammatory responses were also discovered in the
guts of mice (Jin et al., 2019; Lu et al., 2018; Pearl et al., 2011). After 4.1.4. Neurological dysfunction
being treated by MPs (0.5 and 50 µm), there are about 310 gut microbes
were changed by the operational taxonomic unit analysis. Moreover, the 4.1.4.1. In vitro. The nervous system contains a highly complex
hepatic triglyceride and total cholesterol levels decreased in MP-treated network of nerves and specialized neurons that coordinates the action
groups (1000 μg⋅L-1) (Lu et al., 2018). These alterations suggested a long and sensory information across the body. Many researchers have
period of inflammation and increased catalase and superoxide dismut documented neurotoxicity after exposure to MPs in vitro and in vivo
ase activities (Qiao et al., 2019b). In contrast, no inflammation (from the (Guimaraes et al., 2021; Murali et al., 2015). PS-NPs with a diameter
duodenum to the colon) was detected in mice when exposed to PS between 40 and 70 nm could trigger neurotoxicity and alterations in
microplastics (1, 4 and 10 µm, 1.25, 25 and 34 mg/kg bodyweight by metabolic activity in vitro depending on the cell types, concentrations,
oral gavage for 28 days) (Stock et al., 2019). Therefore, the underlying and aggregations (Murali et al., 2015). Guimaraes et al. (2021) also
mechanism for MPs inducing inflammation in rodent models should be found that MP’s neuro-cytotoxic actions as induce apoptosis and ne
investigated in future studies. crosis processes were induced in erythrocytes (MPs: 17.19 µm
± 0.38 µm). Therefore, the necessity of neurological dysfunctions
4.1.3. Immune system dysregulation should be verified by in vivo studies.
4.1.3.1. In vitro. The immune system consists of many biological 4.1.4.2. In vivo. In vivo studies demonstrated that acetylcholinesterase
structures that can prevent organisms from xenobiotic attack (Yu et al., (AChE), a crucial neurotoxicity biomarker, was inhibited by MPs
2018). The systemic immune responses are immediately activated once (1–5 µm) in the brains of European seabass (Dicentrarchus labrax),
MPs induce the inflammation (Choi et al., 2020; Villegas et al., 2021). influencing their swimming behavior (Barboza et al., 2018a, 2018b). A
Choi et al. (2020) confirmed the immunological responses of peripheral similar behavior, the suppression of AChE in the brain, was found within
blood mononuclear cells by the release of immune-related cytokines (e. 2 weeks after exposing the fish O. niloticus to MPs at concentrations of 1,
g., IL-6, TNF-α). IL-6 stimulates the generation of mature T-cells and 10, and 100 mg⋅L-1. The relationship between AChE activity and varia
facilitates the formation of adaptive immune responses during the tions in neuroblasts further confirmed MP’s neurotoxic potential for
exposure process (Claesson-Welsh, 2015). In contrast, TNF-α activates fishes (Guimaraes et al., 2021). For the mammals, exposure to PS MPs
and recruits the immune cells, especially adjusting the differentiation or (2 µm, 8 or 16 mg⋅kg-1; 4–8 weeks) in mice brains could alter the
propagation of macrophages (Tay et al., 2020). expression of neuro-related genes, increase the risks of neuro
inflammation, resulting in the impairments of learning and memory
4.1.3.2. In vivo. Although the contributions of MPs in disrupting the behavior (Lee et al., 2022). Moreover, the changes in AChE activity in
human immune systems are largely unknown, environmental exposures mice’s liver were also found under oral gavage (5 and 20 µm,
to other organisms caused by MPs have been well reported. The particles 0.01–0.5 mg⋅d-1, 30 days), suggesting potential threats on influencing
could favor immunosuppression and trigger abnormal immune re neurotransmitter levels (Deng et al., 2017). Similar to the results in
sponses. Phagocytosis, for example, was dramatically decreased when fishes, neurotoxicity was also discovered by building the association
exposing cationic PS MPs (100–400 µm; 10 mg⋅day-1) to the rainbow between AChE activity and changes in neurotransmitter levels dispersed
trout (Ašmonaitė et al., 2018). The values of some key cytokines, like in mice’s bodies. Prüst et al. (2020) inferred that NPs might have the
IL-6, IFN γ, and TNF α, were stimulated to enlarge when exposure to PS potential to induce the inhibition of acetylcholinesterase activity and
MPs (32–40 µm, 0.1 and 1 mg⋅L-1) (Huang et al., 2020). Meanwhile, altered neurotransmitter levels in the brain based on the results from the
homeostasis could also be disturbed, causing immune system modula nanoparticles of chemically inert metals. Therefore, we speculate that
tion. Exposure of PC and PS NPs to fathead minnow significantly trig MPs might have neurotoxicity on humans, and it should be a priority to
gered the innate immune response in the degranulation of primary realize how MPs caused neurotoxicity in further investigations.
granules and the release of the neutrophil extracellular trap (Greven
et al., 2010). However, the results of Bunge et al. (2022) suggested the
dietary uptake of polyester MPs had limited effects on the immunity of 4.2. Toxicity originated from additives and attached substances
fishes with no significant alterations in immune indexes (head kidney
leucocytes) during the exposure periods (9 weeks). Due to “Trojan horse” effects, many substances (added into or
In addition to marine fish, immunosuppression evidence in mice has attached to MPs) could also be transferred into the human body along
been reported (Jin et al., 2019; Lu et al., 2018; Turner et al., 2019). Lu with the polymer particles (Vethaak and Legler, 2021). Endogenous and
et al. (2018a) discovered a decrease in the mucin 1 secretion, a major exogenous contaminants can also enter the human body in the different
gene related to the immune system, after being exposed to PS MPs in ways described in Section 3. Some additives have also been documented
mice (0.5 and 50 µm, 0.1–1 mg⋅L-1 for 5 weeks). Similarly, another to irritate skin and eyes and disturb the immune system and neurological
mouse experiment also reported a significant decrease in mucus secre dysfunctions (e.g., phthalates, BFRs, TCS, and BPs) (Hazimah et al.,
tion (Kruppel-like factor 4) when exposure to PS MPs (0.5 and 50 µm, 2019; Koelmans et al., 2016). Phthalates are commonly used to enhance
0.1–1 mg⋅L-1 for 6 weeks) (Jin et al., 2019). In contrast, no evidence of the flexibility of plastic without a covalent bond (Posnack, 2021). Since
immunosuppression was found when exposing mice to PS MPs (1, 4, and phthalates account for above 60% of PVC polymers, more than 20 % of
10 µm) with different doses of 1.25, 25, and 34 mg⋅kg-1 bodyweight by dibutyl phthalate (DBP) can release at a high concentration of PS MPs
oral gavage for 28 days (Stock et al., 2019). Some studies often (0.1–5 µm; 20 mg⋅L-1) after 1 h exposure (Teuten et al., 2009). The
concentrated on PS MPs, the immunotoxicity of other plastic types (e.g., released phthalates could cause intestinal accumulations in the gut of
PE, PP, and so on) on human health is also of value for understanding MP mice with the order decreased: DEHP > DBP > DEP > DMP (Deng et al.,
hazards and should be investigated in future studies (Ebrahimi et al., 2020). After exposing DEHP contained MPs for 30 days, a severer in
2022). The occurrence of immunosuppression has been displayed in testinal inflammation was detected compared to only exposure to indi
both fish and mice models, indicating that MPs may induce (or enhance) vidual DEHP. Some BFRs, such as polybrominated diphenyl ethers
immune response and chronic effects on human beings. However, no (PBDEs) and hexabromocyclododecane (HBCD), are incorporated to
observed cohort investigations directly reported on human beings. avoid ignition without chemical polymerization (Posnack, 2021).
However, most BFRs are likely to retain in plastics because of their high
11
hydrophobicity. Although the release fluxes of BFRs from MPs are significant alterations to metabolite profiles, such as disrupting
extremely low (diffusion coefficients: 10-28.30~10-20.84 m2⋅s-1), the host-symbiont signaling (Lanctôt et al., 2020). The energy and lipid
digestive systems of mammals could potentially accelerate their leach metabolism were also affected by MPs in mice models. For instance,
ing (Sun et al., 2019). For example, a significantly high level of PBDE energy homeostasis was disturbed as evidenced by down-regulating the
concentration was found in fish (Japanese medaka) after feeding MPs for relevant biomarkers and enzymes such as adenosine triphosphate (ATP)
2 months (Rochman et al., 2013). Similarly, the PBDE concentrations and up-regulating lactate dehydrogenase; the activities of lipid bio
were higher in rainbowfishes fed by PBDE-contained MPs than by virgin markers (e.g., triglycerides TG; total cholesterol T-CHO) were also
MPs (Hazimah et al., 2019; Wardrop et al., 2016). The release of DEHP decreased (Deng et al., 2017).
and BFRs can lead to a series of detrimental consequences, such as Meanwhile, some hazardous additives, such as the BPs, TCS, and
hepatotoxic, neurotoxic, and even cardiotoxic effects (Rowdhwal and phthalates, can be released during the fragmentation. Generally, about
Chen, 2018). Compared to the phthalates and BFRs, TCS is often added 99.5% of free bisphenol A is metabolized to either bisphenol A sulfate or
to polymer chains by the unique bond rotation entanglements. These bisphenol A glucuronide (Cho et al., 2017), while the primary metabo
connections could increase polymers’ toughness and strength, further lites of the TCS are triclosan sulfate or triclosan glucuronide (Zhang
protecting the polymer structure from microbial erosion. PC is generally et al., 2021a and 2021b). For the representative phthalates, the primary
synthesized from bisphenol A and phosgene/diphenyl carbonate metabolites of DEHP are the hydrolysis products mono-(2-ethylhexyl)
through condensation reactions (Kim, 2020). Although the phthalate (MEHP) and two subsequently oxidized compounds mon
chemical-bonded additives are relatively solid, their pervasive applica o-(2-ethyl-5-hydroxyhexyl)phthalate and mono-(2-ethyl-5-oxoyhexyl)
tion can also cause wide detection in human beings (Braun et al., 2009, phthalate (Kato et al., 2004). These chemicals together with their me
2021b). Bisphenol (BPA) and triclosan (TCS) have been detected in the tabolites could act as endocrine disrupters and produce related disorders
urine of > 90% and ~75% of the US population, respectively (Braun in human beings, especially diabetes, obesity, and reproductive damage
et al., 2009; Weatherly and Gosse, 2017). Therefore, the potential health (Zhang et al., 2021a and 2021b). Therefore, MPs’ combined exposure
risks of BPA and TCS are being evaluated in succession. In vivo and in and additives should draw more attention in future studies.
vitro studies revealed that both BPA and TCS could be converted to
glucuronic or sulfated forms and subsequently excreted in urine with an 4.4. Interaction of MPs with microbes and biomolecules
eliminated half-life of < 6 h and 13–29 h, respectively (Larsson et al.,
2014). Although the leached information is limited, BPA and TCS exert Apart from adsorbing the contaminants from the environments,
endocrine-like effects on the reproductive organs and the nervous sys some organic nutrients can easily be attached to MPs in aquatic envi
tems. Barboza et al., (2020) found a positive relationship between MPs ronments within a few hours, then attract microorganisms to form
(0.15–1.5 mm) and bisphenols in fish (Dicentrarchus labrax, Trachurus biofilms (Yokota et al., 2017). Over prolonged time, the composition of
trachurus, Scomber colias). Both the target hazard quotient and hazard biofilm could contain diverse microbial communities (e.g., bacteria,
ous index were calculated above 1, indicating potential adverse health fungi, and algae) and secret extracellular polymeric substances (Rummel
effects for humans. et al., 2017). On the one hand, the substances change the physi
On the other side, MPs can work as vectors and enrich the contam ochemical properties of MPs, which further increases the probability of
inants from the environments by several orders of magnitude, affecting being ingested. On the other hand, the microbes attack the polymer
the MPs’ bioavailability in aquatic organisms (Ho and Leung, 2019). For backbone, causing biodegradation and release of the oligomers, mono
instance, the digestive fluid can accelerate the desorption of many hy mers, and even additives. For example, Kalčíková et al. (2020) found
drophobic organic compounds (HOCs) from the MPs, further increasing that the biofilm-attached MPs (180.5 ± 118.7 mm) could adsorb nearly
the bioavailability of the contaminants (Bakir et al., 2014; Wu et al., 1.5 times higher silver in seven days than pristine MPs. Comparative
2020b). Wu et al. (2020b) found no adsorption/desorption hysteresis investigations revealed that the adsorption capacity for Pb was
generated in the stimulated intestinal conditions, implying a higher risk enhanced by two times. Non-analogously, biofilm can bias the adsorp
of bisphenols-contaminated PVC MPs (~13.2 µm) in human breast cells. tion capacity of HOCs by increasing the mass transfer resistance of the
Some harmful substances, such as bacterial pathogens and antibiotic plastics. Jin et al. (2020) reported that the sorbed PCBs declined
resistance genes, could also spread disease among the biotics (Vethaak significantly in summer and vice versa in winter due to microbial as
and Legler, 2021). Moreover, it has been reported that polypropylene semblages affected by different temperatures. The uncertainty of
(PP) transmitted the genus Vibrio as a pathogenic bacterium causing adsorption capacity further contributes to the unpredictability of eco
coral disease (Bourne et al., 2015). Another study also reported an toxicity. Although there is growing evidence that MP biofilms may in
apparent alteration in the gut microbiome’s activities, resulting in a crease the risk of disease in humans, research on the link between
sudden proliferation, pro-inflammation, and endotoxemia of opportu adverse effects and biofilm-associated MPs is still limited. Future
nistic species (Zhu et al., 2018). On the other side, the ingestion of MPs research is required to clarify the mechanisms of interactions among
has been certified to reduce the external polychlorinated biphenyls MPs, biofilm-colonizing microorganisms, and chemical pollutants.
(PCBs) concentration in the fish model by weakening their bio Once the size of plastics drops to the nanoscale, a protein coat known
accessibility (Diepens and Koelmans, 2018). Although no literature has as “corona” can quickly form when they enter the biological fluids (e.g.,
evidenced this transmission route can happen in human beings, the serum and cytoplasm) (Galloway et al., 2017). The NP surface interacts
infective possibility should not be ignored and addressed in future with various biomolecules in addition to proteins and is rapidly coated
studies. by the proteins, polysaccharides, lipids, and others to form a biomole
cule corona (Fig. 4). Although little knowledge about how the individual
4.3. Metabolomics analysis of the MPs molecules in protein corona contribute to the interactions, it has been
believed that the corona critically affects the interactions between NPs
The metabolism processes of MPs are of great necessity for better and living systems. These adsorbed molecules further alter the persis
realizing the underlying mechanisms for the adverse effects on human tence, bioavailability, and ecotoxicity of NPs (Monopoli et al., 2012;
beings, which might be related to their shapes, concentration, and sizes Tenzer et al., 2013). Tenzer et al. (2013) investigated the corona for
(Lanctôt et al., 2020). Microfiber showed higher toxicity than mation around PS NPs in the plasma and found that the corona can in
particle-shaped MPs, which could down-regulate fatty acyl metabolism crease their aggregation in prolonged exposure and ultimately reduce
associated with nutritional deficiency and up-regulate glycer endothelial cell death. Another study revealed that this “natural func
ophospholipids metabolism (Zhao et al., 2021b). Even at a relatively low tionalization” could comfort the cellular uptake and decrease related
concentration (5000 μg⋅L-1; 5 items⋅mL-1), PE microspheres could elicit toxicity (Monopoli et al., 2012). In contrast, research reported the
12
Fig. 4. The formation of biomolecular corona on NPs. The

NP surface interacts with various molecules and is rapidly
coated by the proteins (protein-corona), as well as other
biomolecules, including proteins, polysaccharides, lipids,
etc., to form a biomolecule corona. The corona critically
affects the interactions between NPs and living systems,
such as camouflaging the foreign particles to enter or cross
cells. These mixtures of adsorbed molecules further alter
the persistence, bioavailability, and ecotoxicity of NPs.
greater uptake of MPs after being camouflaged by the corona, thereby of MPs to humans. Although the accurate evaluation of the human risks
promoting the cellular internalization of MPs. The internalization could is lacking, some implications could also be provided based on in vitro and
further influence the translocation of MPs (~ 3 µm) into tissues, finally in vivo results (Rubio et al., 2020; Wang et al., 2021; Wright and Kelly,
causing toxicological effects on human health (e.g., inflammation) 2017). In in vitro studies, MPs can potentially penetrate the human cell
(Ramsperger et al., 2020). This feature may assist nanoparticles to cross membrane, and then produce ROS, induce inflammation, activate im
the natural barriers in the human body, including the blood-brain bar mune responses and trigger neurotoxicity at molecular levels (Huang
rier (Onyema et al., 2021). Hollóczki and Gehrke (2019a) predicted that et al., 2021b). In vivo studies containing animal models could offer more
NPs (5 nm) were susceptible to denature proteins by changing their realistic significance to health risks. Based on genetic homology, a recent
structures fundamentally. Computational analysis showed that PE NPs study built an extrapolation algorithm from mice to humans according
could interplay with cell membranes and change the lipid bilayer to some sensitive biomarkers (e.g., ATP, TG, CAT) (Yang et al., 2019).
structure (Hollóczki and Gehrke, 2019b). However, there is a lack of The study first investigated the acceptable threshold concentrations of 5
experimental evidence regarding the interaction between NPs and bio and 20 µm MPs for mice were 7.90 ± 4.57 and 0.71 ± 0.14 μg⋅g− 1, and
molecules in the human body. Therefore, more fundamental knowledge then extrapolated the values to humans being 53.26 ± 32.54 mg⋅g-1
on the formation of corona and the potential risks at the cellular level (5 µm) and 5.06 ± 1.00 mg⋅g-1 (20 µm) toxicokinetic/toxicodynamic
and in the vital organs deserves more studies. studies (Yang et al., 2019). The results provide further insights into
discovering the role of MPs resulting in ROS generation, inflammation,
5. Excretion of MPs from the human body immunosuppression, and neurological dysfunctions in the human body
(Bouwmeester et al., 2015; Elizalde-Velázquez and Gómez-Oliván,
Micro- and nano- polymers can pass into the small intestine through 2021).
the bile and larger fragments may be excreted through urine and feces Based on the in vitro and in vivo results, a rough conclusion could be
(Winther, 2019, 2021b). Another investigation found a wide range of drawn that higher hazards may generate under the exposure of smaller
MPs (0.8–41.6 items⋅g-1) in stool samples (Schwabl et al., 2019). size, higher dose, more elongated and additive-contained by various
Because most polymers are biologically inert, their elimination path chemical nature of MPs. In detail, the smaller MPs (< 10 µm) can
ways can also be extrapolated from other inert micro- or nanoparticles. internalize the cell cytoplasm or cross the barriers of intestines and lungs
Some digestive enzyme-degraded MPs (or corona attached MPs) may more easily at molecular or organ levels despite that some conflicting
become hydrophilic and be eliminated in urine or feces. If the polymers cases happened might be attributed to the stronger aggregation effects of
are hard to degrade, they could directly end up in the feces (Schwabl NPs than MPs; A clear dose-dependent effect of MPs could be summa
et al., 2019, 2021b). MP size also determines their clearance properties rized. With higher dosages, MPs have larger opportunities to interact
(Dawson et al., 2018). Some larger NPs (>144 nm) seem to be actively with the cells or animal models (e.g., human cells, fishes, mice). When
evacuated after passing the gut blood barrier and entering the liver considering the humans, the result seems still stands as a significant
through the bloodstream. These NPs are filtered by the liver and trans positive correlation between the concentration of MPs and several dis
ported into the digestive tract through the bile and intestinal wall eases (e.g., IBD, interstitial lung disease). MPs with a higher length-to-
(Dawson et al., 2018; Lu et al., 2016). For some finer ones (<10 nm), diameter ratio can be help of penetrating the intestine and cardiovas
they can further penetrate into the kidney and finally be eliminated via cular system, but it is not conclusive that fiber-like MPs are more per
the renal pathway (Du et al., 2018). Furthermore, NPs can be excreted ilous on humans because of no direct evidence (e.g., epidemiological
via tears, saliva, sweat, and breast milk. However, due to the lack of investigation). Higher levels of hazards occurred on the biotics
corresponding studies, the excretion routes still need validation. depending on the polymer nature with higher molecular weights and
cationic charge densities (Cormier et al., 2021; Fischer et al., 2003).
6. Potential health implications from the in vitro and in vivo Moreover, the composition-dependent variations of MPs could also lead
studies to the species-specific toxicity of various degrees, which could be
attributed to the “trojan horse” effects (Kim et al., 2020; Zhao et al.,
ADMET processes implied that MPs can possibly accumulate and 2021a). The attached substances, including the endogenous and exog
affect human health through the three exposure pathways (e.g., inges enous contaminants, could change the bioavailability of MPs (Kim et al.,
tion, inhalation, and dermal contact) (Vethaak and Legler, 2021). 2020; Zimmermann et al., 2020). This is of great concern because many
Among them, ingestion and inhalation play critical roles in the exposure of the contaminants have been certified to cause human health effects,
13
such as the immune system and neurological dysfunctions (Hazimah MPs.

et al., 2019; Koelmans et al., 2016). Whether the presence of direct
transfer of contaminants from MPs to human tissues is still controversial. Environmental Implication
This is because the retention time of MPs in human remains unclear,
which directly influence the release of contaminants, although the MPs The manuscript has significant implications for understanding the
can stay more than 6 days in the fish gut (Grigorakis et al., 2017) or 17 harmful role of MPs as perpetrators and/or vectors in the biosphere. It
days in mice’s tract (Yang et al., 2019). Therefore, the health risks of can help determine the exposure routes and levels on human beings,
MPs to humans remain unclear and need to go further in our under including the ineluctable annual MP intake through the ingestion,
standing of underlying mechanisms. inhalation, dermal contact and trophic transfer; explore the known
factors and the knowledge gaps in ADMET processes of MPs; provide the
7. Future directions of research on microplastics in human foundations as pioneering interdisciplinary research for the scientific
health community to discover the MP-related health issues; and understand the
physical, chemical and biological interactions of MPs with body systems.
Despite a growing body of studies on MPs, there are still considerable
research gaps in their ADMET processes. Knowledge of the processes can Funding
assist in the understanding of the exposure, fate, and ecotoxicity of MPs
in individuals and facilitate technical approaches to reduce plastic This work is supported financially by the National Natural Science
pollution. According to the literature discussed above, we identified the Foundation of China (NSFC: 22106130), the internal grant (RC-SGT2/
following research priorities. The first one is the accurate estimation of 18-19/SCI/008) from Hong Kong Baptist University and General
the abundance of MPs absorption in individuals. Recent methodologies Research Fund (12303321) from University Grants Committee of Hong
are not unified and often underestimate the occurrence of MPs due to the Kong SAR.
limitation in counting some tiny plastics (<1 µm). Therefore, developing
more advanced techniques for accurately quantifying MPs’ uptake,
Declaration of Competing Interest
distribution, and elimination rates in individuals is urgently needed.
Following that, the uptake of MP abundance through ingestion, inha
The authors declare that they have no known competing financial interests or personal
lation, and dermal contact should be evaluated. More studies on the
relationships that could have appeared to influence the work reported in this paper.
trophic transfer of the MPs are needed to identify their transfer effi
ciency and potential effects on the food web (bioaccumulation and
Data Availability
biomagnification). Moreover, our understandings of MP-induced eco
toxicity are still at an early stage, especially in neurological dysfunction
No data was used for the research described in the article.
and immune system dysregulation. Due to their release and adsorption
properties, a study of MPs metabolism needs to consider both the ad
Appendix A. Supporting information
ditives and exogenous contaminants. The induced ecotoxicity should be
the combined results affected by the bioavailable variation of the
Supplementary data associated with this article can be found in the
mixture, while mounting studies used the pristine models. In addition to
online version at doi:10.1016/j.jhazmat.2022.129361.
the physical hazards, MPs’ chemical and microbiological interactions
should also be addressed. This is particularly true for the intricate mi
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Journal of Hazardous Materials 437 (2022) 129361

Contents lists available at ScienceDirect

Journal of Hazardous Materials

Absorption, distribution, metabolism, excretion and toxicity of

• Absorption, distribution, metabolism,

1. Introduction metabolization, unlike the reported “Trojan horse” effects of trans

Fig. 4. The formation of biomolecular corona on NPs. The

such as the immune system and neurological dysfunctions (Hazimah MPs.

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Journal of Hazardous Materials 437 (2022) 129361

Contents lists available at ScienceDirect

Journal of Hazardous Materials

Absorption, distribution, metabolism, excretion and toxicity of

• Absorption, distribution, metabolism,

1. Introduction metabolization, unlike the reported “Trojan horse” effects of trans­

Fig. 4. The formation of biomolecular corona on NPs. The

such as the immune system and neurological dysfunctions (Hazimah MPs.

You might also like

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

1. Introduction metabolization, unlike the reported “Trojan horse” effects of trans