Critical Review

Cite This: Environ. Sci. Technol. 2019, 53, 1748−1765 pubs.acs.org/est

Emergence of Nanoplastic in the Environment and Possible Impact

on Human Health
Roman Lehner,† Christoph Weder,† Alke Petri-Fink,†,‡ and Barbara Rothen-Rutishauser*,†
†
Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, Switzerland
‡
Chemistry Department, University of Fribourg, Chemin du Musée 9, 1700 Fribourg, Switzerland

ABSTRACT: On account of environmental concerns, the fate and

adverse effects of plastics have attracted considerable interest in the
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past few years. Recent studies have indicated the potential for
fragmentation of plastic materials into nanoparticles, i.e., “nano-
plastics,” and their possible accumulation in the environment.
Nanoparticles can show markedly different chemical and physical
properties than their bulk material form. Therefore possible risks and
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hazards to the environment need to be considered and addressed.

However, the fate and effect of nanoplastics in the (aquatic)
environment has so far been little explored. In this review, we aim to
provide an overview of the literature on this emerging topic, with an
emphasis on the reported impacts of nanoplastics on human health,
including the challenges involved in detecting plastics in a biological environment. We first discuss the possible sources of
nanoplastics and their fates and effects in the environment and then describe the possible entry routes of these particles into the
human body, as well as their uptake mechanisms at the cellular level. Since the potential risks of environmental nanoplastics to
humans have not yet been extensively studied, we focus on studies demonstrating cell responses induced by polystyrene
nanoparticles. In particular, the influence of particle size and surface chemistry are discussed, in order to understand the possible
risks of nanoplastics for humans and provide recommendations for future studies.

1. INTRODUCTION (although there is an increasing trend toward using biobased

Synthetic polymers are one of the most important classes of feedstocks),4 and their immense utility is based on their vast
materials of the 21st century and impact our society and daily range of chemical and physical properties that can be accessed
life in ways that cannot be overestimated.1 The properties of and their low production and processing costs. This makes
polymers are directly linked to their macromolecular polymeric materials useful for manifold applications that range
architectures, which can readily be varied in a broad parameter from packaging materials to toys and sporting goods to medical
space. As a result, a plethora of synthetic polymers have been devices and construction materials.5−7 Commercially used
developed that cover a broad range of attractive mechanical polymers are always formulated with additives such as
and other characteristics, including many property combina- stabilizers, flame retardants, plasticizers, fillers, and pigments,
tions that cannot be accessed with naturally occurring which contribute to the overall materials properties.8 Although
polymers such as proteins and cellulose.2 The large family of additives are typically present in much smaller amounts than
synthetic polymers has traditionally been classified into four the polymer, they are not necessarily benign and can have an
groups, namely, (i) thermoplastic polymers or “plastics”, i.e., adverse effect on the environment.9 The production of
polymers that melt above a specific temperature and can be polymers, including thermoplastics, thermosets, and elasto-
shaped before solidification upon cooling; (ii) thermosetting mers, as well as biodegradable and biobased plastics, has
polymers or “thermosets”, which are provided as (normally increased significantly over the past 60 years (Figure 1). In
liquid) precursors and are irreversibly cured after shaping 2016, around 335 million metric tons of polymers used as
through a chemical reaction into an infusible, insoluble plastics were produced worldwide, representing trillions of
polymer network; (iii) elastomers; and (iv) synthetic fibers.3 dollars in terms of global economic returns, with China being
Strictly speaking, only group (i) and subsets of groups (iii) and the leading producer.10
(iv) display thermoplastic character and should thus be Growing production also leads to an increase of plastic waste
referred to as “plastics”. However, as an overwhelming majority and, unfortunately, also promotes widespread accumulation in
of polymer particles in the environment stem indeed from
thermoplastic materials, the environmental science community Received: September 30, 2018
has adopted the practice of referring to all polymers as Revised: December 23, 2018
“plastics”; we follow this convention herein as well. Polymers Accepted: January 10, 2019
are still mainly derived from petroleum-based raw materials Published: January 10, 2019

© 2019 American Chemical Society 1748 DOI: 10.1021/acs.est.8b05512

Environ. Sci. Technol. 2019, 53, 1748−1765
Environmental Science & Technology Critical Review

Figure 1. Polymer production worldwide and in Europe, including thermoplastics, polyurethanes, and other polymers (thermosets, adhesives,
coatings, and sealants) but not polyethylene terephthalate (PET), polyamide (PA), polypropylene (PP), or polyacrylic fibers. The growth rate of
polymer production in Europe has stabilized in the past decade, which is related to the effects of the economic crisis of 2007−2008, as well as
higher energy and raw material prices leading to higher product prices and decreasing competitiveness with the flourishing Middle Eastern plastics
industry. Numbers adopted from PlasticEurope.11

the environment, where the material can become brittle and formation of nanosized polystyrene particles after 4 weeks of
start to fragment. In the environment the degradation of exposure in a weathering chamber.19
macroscopic plastic objects (>5 mm) into smaller pieces, often Several studies have been published in the past few years
referred to as microplastics, typically occurs by a combination estimating the mass of the overall global plastic waste as well as
of chemical and physical processes that notably can involve the mass of plastic waste entering our oceans (Figure 2), which
photodegradation, oxidation, hydrolytic degradation, and are considered to be the global ecosystem that is mostly
mechanical disintegration. These processes are collectively
affected by plastic waste. In 2009, Barnes et al.20 estimated that
referred to as weathering and, depending on the polymer type
and morphology, can differ significantly.12,13 Photodegradation plastic materials constitute 10% of the total discarded waste.
caused by the ultraviolet (UV) portion of sunlight generally Jambeck et al.21 presented numbers in the range of
initiates the weathering process; this radiation is capable of
breaking chemical bonds in synthetic polymers.14 The process
affects not only the polymers themselves but also additives
implemented within the materials, resulting in changes in their
chemical structure and physical properties. Oxygen can
increase the absorption of UV radiation by the formation of
a complex with conjugated unsaturated hydrocarbons, thereby
accelerating the degradation process.15 In addition, polymers
such as polyesters or polyamides can also be degraded by
hydrolysis, i.e., the cleavage of ester or amide bonds by
reaction with water.16,17 These chemical degradation processes
cause a reduction of the polymer molecules’ molecular weight.
Eventually this leads to a reduction of mechanical strength and
in many cases an increased absorption of water, which causes a
further reduction of the mechanical properties and creates bulk
and surface stress gradients, which eventually lead to cracking
of the material. External mechanical forces also contribute to
the fragmentation into smaller pieces, whose dimensions
gradually diminish over time. The degraded plastic pieces form
a highly heterogeneous collection, varying in size, shape, and
density as well as the chemical composition of the specific Figure 2. Plastic sample taken from an expedition in the Ligurian Sea
material. in May 2018 by the “Sail and Explore Association” using a manta
Newest observations studying the degradation of poly- trawl during 30 min with a mesh size of 0.3 mm. The Mediterranean
Sea represents one of the most polluted seas worldwide with nearly
ethylene microplastic pellets have shown that already an four times higher concentrations of microplastic fragments compared
exposure time of 8 weeks in artificial seawater induces severe to the North Pacific Gyre and a record-breaking number of 1.25
microcracking of the pellets surfaces, which, in combination million microplastic fragments per square kilometer floating.53
with mechanical forces, can break down the material into Reprinted with permission from Sail and Explore Association,
smaller sized particles.18 Further studies also revealed the Copyright 2018.

1749 DOI: 10.1021/acs.est.8b05512

Environ. Sci. Technol. 2019, 53, 1748−1765
Environmental Science & Technology Critical Review

4.8−12.7 million tons of mismanaged plastic waste that was It is apparent that the pollution of oceans with plastic has
generated in 192 coastal countries and discarded into the become a major environmental issue. Although the long-term
oceans in the year 2010. In addition, based on data collected in impact of micro- and nanoplastics in the (aquatic) environ-
24 expeditions conducted during 2007−2013, Eriksen et al.22 ment is still difficult to predict, this aspect might prove to be a
reported that a minimum of 5.25 trillion plastic particles with a significant challenge to our society.54 The purpose of this
weight of up to 270,000 tons are floating in the world’s oceans. review is to provide an overview of current knowledge specific
Another study reported the number of small plastic particles to nanoplastics and their impact on the environment and
(nominally <200 mm) to be in the range of 15−51 trillion, human health. We briefly discuss sources and nanoplastic
with a collective weight of 93,000 to 236,000 tons, which formation in the aquatic environment and the impact of
corresponds to approximately 1% of the global plastic waste nanoplastics on aquatic species and human exposure which is
entering the oceans in the year 2010.23 A recent study from most likely via seafood. Furthermore, we will focus on possible
2018 predicted, using data received from multivessel and entry routes of nanoplastics into the human body focusing on
aircraft surveys in the so-called “Great Pacific Garbage Patch”, the cellular level.
that at least 79 thousand metric tons of ocean plastic are
floating inside an area of 1.6 million km2, which correlates to 2. SOURCES AND FATE OF PLASTIC IN THE
numbers 4−16 times higher than previously reported.24 Other ENVIRONMENT
studies have also proven the occurrence and accumulation of
large plastic items in the deep sea,25−27 and recently published The accumulation of plastics and their degradation products in
data show that plastic objects have been ingested by animals of the environment has continuously increased in recent decades,
the benthic zone, assuming a sedimentation behavior of the which is unsurprising given that 50% of plastic products are
plastic particles.28,29 Sedimentation of plastic particles is only produced for single-use applications and are soon discarded.55
possible if the density of plastics is higher than that of seawater Discarded packaging plastics account for a significant part of
(which is the case for roughly a third of all polymers produced) the total solid waste that ends up in landfills, where, depending
or if they become negatively buoyant by the formation of on their composition, they remain unchanged or may degrade
biofilms and adherence to other particles.30−33 The smaller the into fragments upon microbial heat production and further
particles are, the faster they can reach their critical sinking biodegrade to carbon dioxide and water.56 Macroplastics
density.34 Plastic particles are also deliberately added to represent the main source of plastic litter. Once in the
personal care products.35 A threat that has thus far been environment they can lead to entanglement and, despite their
underestimated is the impact of microplastics in soils, size, being ingested and retained by various species, including
sediments, and freshwater on the terrestrial ecosystem.36 seabirds, fish, and cetaceans, which then often die from related
Research has only recently begun in this direction, as an causes such as starvation.57,58 Microplastic particles affect an
estimated 80% of microplastic pollution in the oceans even greater number of organisms, including primary
originates from land.37,38 consumers of the food chain such as zooplankton, bivalves,
In the past decade, much attention has been paid to the and small fish.59−61 It has been shown that (fragments of)
formation of microplastics. The exact definition of these textile fibers with dimensions in the micrometer range, which
particles differs but generally includes particles with are disengaged from clothes during washing, are not removed
dimensions between 1 μm and 5 mm.39 The first small plastic by the filter systems of wastewater treatment plants and
particles (<5 mm) were detected in open waters in the therefore end up in the environment.62 In addition, personal
1970s.40,41 Recent studies confirmed the expectation that the care products such as toothpastes and facial scrubs often
degradation process of plastic particles does not stop at the contain polyethylene-based microplastic particles which then
micrometer level and that plastic microparticles continue to end up in the wastewater.63 The presence of microplastics has
disintegrate to form plastic nanoparticles.19,42,43 Such nano- been reported all around the globe, from polar regions frozen
particles usually exhibit different chemical and physical in arctic ice to the open water around the equator, and from
properties than macroscopic objects based on the same coastal areas down to the deep sea.30,64 The process of plastic
material.44 In addition, their interactions with living organisms degradation progresses with increased time in the environment
can also greatly differ.45 Thus, the differences between micro- and may eventually lead to the formation of nanoparticles.65
and nanoplastics are not trivial, and the interactions of For example, a recent study by Lambert et al. demonstrated the
nanoplastics with the environment and organisms are a specific formation of plastic nanoparticles under laboratory conditions
concern.46 Like plastic microparticles, nanoplastics can adsorb when disposable polystyrene coffee cup lids were exposed to
and carry hydrophobic chemicals that have a potential UV light.19 This observation supports the notion that wherever
biological and toxicological impact on the environment, such polymeric objects are released in the environment, the
as polychlorinated biphenyls (PCBs) released from objects like degradation to nanoplastic should a priori be considered. At
electrical devices, inks, paints, or the pesticide dichlorodiphe- the same time, it is clear that the degradation pathways of
nyltrichloroethane (DDT).47−49 A clear understanding of the different polymer types can vary significantlywhile some
interaction of nanoplastics with the environment, especially polymers degrade into nanoparticles, others are known or can
with living organisms, is important to assess possible health be expected to form water-soluble fragments. From exper-
hazards, because nanoplastic particles can react differently than imental observations made so far, it can be estimated that
their micronsized counterparts. However, current research plastic nanoparticles can be released into the environment as
aimed at addressing the effects of plastic is focusing mainly on “primary”, i.e., intentionally manufactured particles for
aquatic systems and only limited data are available regarding industrial purposes, e.g., paints, adhesives, electronics, and
the impact of nanosized plastic particles on human health,50,51 cosmetics, and/or emerge as “secondary particles” as a result of
although their formation in the environment is increasing and the degradation of larger plastic objects.66−68 Primary
thus also the possible transfer to humans via the food chain.52 nanoplastics used in households and industry are most likely
1750 DOI: 10.1021/acs.est.8b05512
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not being collected by the wastewater treatment facilities and exposed for 96 h to a range of concentrations of 110 nm
are thus discharged as sewage into the aquatic environment. polystyrene particles (from 0.05 up to 50 mg/L), to
However, our current knowledge of nanoplastics in the carbamazepine (6.3 μg/L) alone and to a mixture of
environment is still very limited and only a few scientific polystyrene + carbamazepine (0.05 mg/L + 6.3 μg/L).
publications are available. In addition, the literature remains Observations of different biomarkers from the digestive glands,
inconsistent about the categorization of the particle sizes.39 A gills, and hemolymph were conducted. After exposure to
number of studies have set the upper size limit of nanoplastics polystyrene, carbamazepine, and their mixture, clear evidence
at either 100 or 1000 nm. A recent publication by Gigault et al. for genotoxicity was found in hemocytes as well as significant
proposes an appropriate definition of nanoplastics on the basis downregulation in gene expression after combined exposure of
of physical and chemical properties. According to the authors, polystyrene and carbamazepine. Moreover, it could be shown
a nanoplastic is defined as “particles within a size ranging from that even at the lowest concentrations tested, polystyrene
1 nm up to 1000 nm resulting from the degradation of nanoparticles can induce oxidative damage.82 Della Torre et al.
industrial plastic objects and can exhibit a colloidal demonstrated that the accumulation of 50 nm amino-modified
behaviour“.69 One could, however, recommend the use of polystyrene nanoparticles at tested concentrations of 1−50 μg/
the official EU recommendation on the definition for mL in sea urchin embryos induced changes in gene expression
nanomaterials, i.e., “A natural, incidental or manufactured and embryotoxicity.83 A recent study investigated the effects of
material containing particles, in an unbound state or as an 75 nm polystyrene nanoparticles at concentrations between 10
aggregate or as an agglomerate and where, for 50% or more of and 400 mg/L on the physiological changes (i.e., survival) and
the particles in the number size distribution, one or more expression levels of stress defense genes of Daphnia pulex. The
external dimensions is in the size range of 1 nm−100 nm”.70 expression of the gene encoding the energy-sensing enzyme
Another difficulty is that currently no detection method can AMPK (adenosine monophosphate-activated protein kinase)
confirm the presence of nanoplastic components in the was influenced by the nanoplastic in different age groups.
environment.71 Thus, age must be considered as a factor of great relevance
2.1. Effects of Nanoplastics on the Aquatic Environ- when predicting toxic effects.84
ment. Numerous studies have shown that macro- and Effects of nanoplastic on the innate immune system of fish
microplastics can have a significant adverse impact on the have been reported by Greven et al., indicating that the stress
aquatic environment and have been reported elsewhere in response to polystyrene and polycarbonate nanoparticles could
detail.72−74 But what are the effects of nanoplastic particles on stimulate the degranulation of primary granules, oxidative burst
the aquatic environment? activity, and neutrophil extracellular trap release.85 Experi-
In recent years several experimental studies using model ments with zebrafish revealed that after 7 days of exposure to
polystyrene nanoparticles have emphasized that various fluorescent polystyrene nanoparticles with a diameter of 70 nm
organisms such as daphnia, mussels, zooplankton, and algae and at concentrations between 0.025 and 0.2 μg/μL,
can actively ingest nanoplastic particles or adsorb them to their inflammation and lipid accumulation in the liver occurred.86
surfaces.75−78 Marques-Santos et al. investigated the effect of 50 nm amino-
In a laboratory setting, the effects of amino-functionalized modified polystyrene particles at concentrations of 1−25 μg/
polystyrene nanoparticles with a diameter of 50 nm and mL on sea urchin Paracentrotus lividus immune system cells
concentrations between 1−50 μg/mL have been investigated (coelomocytes) in the presence of celomic fluid and at
in the hemocytes of the marine bivalve Mytilus galloprovincialis different particle concentrations. Amino-modified polystyrene
by Canesi et al.79 The hemocytes were exposed to different particles acquired a protein corona once incubated with
concentrations of amino-functionalized polystyrene particles, celomic fluid, dominated by the toposome precursor protein,
which stimulated an increase in extracellular reactive oxygen which triggers particle−coelomocytes interactions and tox-
species and lead to apoptosis within 1 h of exposure. This rapid icity.87
response is in line with the physiological role of hemocytes in Wegner et al. showed that 30 nm polystyrene nanoparticles,
cell-mediated immunity. Sun et al. showed that nanoplastic that were tested at concentrations of 0.1−0.3 g/L, have an
particles at a size of 50 nm and a concentration of 80 mg/L adverse effect on the feeding behavior of the blue mussel
induce toxicity related to oxidative stress toward marine Mytilus edulis because of a reduced filtering activity in the
bacterium Halomonas alkaliphila compared to microplastic presence of the particles.88 Pitt et al. investigated the potential
particles at a size of 1 μm. Furthermore, amine-modified 50 nm toxicity of polystyrene nanoparticles in developing zebrafish
polystyrene nanoparticles induced higher oxidative stress (Danio rerio) and characterized the uptake and distribution of
toward bacteria than that induced by nonmodified particles.80 the particles within embryos and larvae. Embryos at 6 h
The toxicity of amine-modified polystyrene particles was postfertilization were exposed to 51 nm polystyrene nano-
further proven by Tallec et al. Exposure of 50 nm polystyrene particles (approximately 1 mg/(g of fish)) up to 120 h
nanoparticles at concentrations between 0.1 and 25 μg/mL to postfertilization. At 24 h postfertilization the particles could be
Pacific oysters (Crassostrea gigas) showed an increase in found in the yolk sac and had migrated to the gastrointestinal
toxicity for both gametes and embryos in comparison to tract, gallbladder, liver, pancreas, heart, and brain between 48
nonmodified particles. Overall, their data highlight that and 120 h postfertilization. In addition, it could be seen that
exposures to polystyrene nanoparticles may have deleterious the particles altered larval behavior as evidenced by swimming
effects on planktonic stages of oysters.81 Brandts et al. hypoactivity in exposed larvae.89 An initial study of the effect of
investigated the effects of polystyrene nanoparticles, individ- nanoplastic particles delivered through the food chain (algae−
ually or combined with carbamazepine, on the mediterranean zooplankton−fish) on the brain tissue of fish was conducted by
mussel Mytilus galloprovincialis. Carbamazepine is among the Mattsson et al. They showed that 52 nm positively charged
most commonly detected drugs in the environment and may amino-modified polystyrene nanoparticles above 0.075 g/L are
adsorb onto nanoplastics. For this purpose, mussels were toxic to Daphnia magna and that fish eating nanoplastic
1751 DOI: 10.1021/acs.est.8b05512
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contaminated Daphnia showed behavioral disorders. Further-

more, polystyrene nanoparticles were detected in the brain
tissue of all fed fish using hyperspectral imaging. This finding
proves for the first time that plastics nanoparticles can be
transported across the blood−brain barrier in fish.90
The majority of the mentioned studies showing an adverse
effect on different organisms were conducted using amino-
modified polystyrene nanoparticles and concentrations which
are not environmentally relevant as they are all too high. The
amino modification induces a positive surface charge to the
particles, which is experimentally interesting to test charge
effects. Nevertheless, it is well-known from the field of
nanomedicine that aminated surfaces are mainly used for
coupling to, e.g., proteins or antibodies and that the positive
charge of cationic polymers can facilitate cellular uptake and Figure 3. Schematic illustration showing the three major pathways of
endolysosomal escape, thereby overcoming major cellular human exposure to nanoplastics, i.e. via (A) the lung, (B) the
barriers and consequently increasing the possibility for further gastrointestinal (GI) tract, and (C) the skin.
intracellular reactions.91 The most important class of plastic
materials containing nitrogen in the form of amides is scenarios that involve nanoplastic-containing aerosols,97
polyamides. These can be hydrolyzed to afford amines, but it whereas potential contact with the skin can occur through
is not entirely clear to what extent the amines remain intact the use of personal care products such as nanoplastics-
(depending on the type, they may be protonated and containing skin care and cleansing products, or contaminated
oxidized). However, polyamides are not widely used as water or air. According to the current knowledge, ingestion of
packaging materials, and therefore amine-containing nano- nanoplastic particles is likely to represent the main route of
plastic particles stemming from polyamides are not expected to entry, since nanoplastic particles can be ingested by eating
be a major environmental factor. seafood or drinking contaminated water. In addition, nano-
Additionally, nanoplastic particles in the environment will plastic uptake and accumulation, as well as trophic transfer of
most probably interact with their surroundings, leading to nanoplastic within aquatic organisms has been demonstrated
homo- or heteroagglomerates composed of different constit- under experimental conditions, thus fortifying the possibility
uents, due to the size and hydrophobic properties of the that nanoplastics might accumulate in the food chain, and thus
materials.92,93 This might lead to the formation of a surface result in human exposure.98,99 Microplastic particles have
corona of various adsorbed molecules evoking a change of the already been found in several seafood species, such as fish,
physical and chemical parameters as well as a reduced surface- shrimps, and bivalves, but also in other foods, such as honey,
area-to-volume ratio, thus changing their biological activity and beer, salt, and sugar.60,100−104 Recent studies using FTIR
maybe affecting their sedimentation properties.94 These facts spectroscopy have also shown the existence of microplastics in
have to be considered for experimental approaches regarding tap water and bottled water as well as drinking water from
influences on aquatic systems, in order to mimic natural groundwater sources. Out of 159 samples of globally sourced
conditions as closely as possible. tap water, 81% were found to contain microplastic particles,
For nanoplastics, uptake by several aquatic species, the mainly fibers smaller than 5 mm with an overall mean of 5.45
adsorption of hydrophobic persistent organic pollutants particles/L.105 From a total of 259 individual bottles of water
(POPs), and the leaching of chemicals and POPs have been from 11 different brands and 27 different lots, 93% showed
demonstrated, highlighting their potential biological and signs of microplastic contamination with an average of 10.4
toxicological impacts on the environment.95 particles/L.106 Analysis of groundwater from the northwestern
However, a number of studies showing adverse effects such part of Germany revealed that an overall mean of 0.7
as reactive oxygen species production and reproductive microplastics/m−3 can be found.107 These studies reiterate
malfunctioning upon exposing aquatic organisms to nano- that the occurrence of nanoplastics in various food products
plastics have used concentrations several orders of magnitude cannot be ruled out. Unfortunately, there are currently no
higher than concentrations predicted to be environmentally routine methods available that permit detection of nanoplastics
relevant such as 1 pg L−1 to 15 μg L−1 for nanoplastics at sizes in foods, and as a result, no data are available that go beyond
of about 50 nm.96 Reflecting this fact will help to understand the above-mentioned research works.
the impact of environmentally relevant nanoplastic concen- Human health might also be affected due to the transfer or
trations. In addition, there is a lack of knowledge regarding leaching of chemical additives from the plastic material itself.
how nanoplastics (and hitchhikers) are transferred up the food Within the plastic manufacturing process, chemicals such as
chain and how they accumulate and interact with the plasticizers, pigments, or stabilizers are added to give the
environment, especially with living organisms. Thus, the desired properties of the final product, e.g., their flexibility,
impact of a contaminated food chain on humans and the color, and stability. Nowadays, thousands of different
resulting health hazards are not at all clear. chemicals are currently used for these purposes, and it is
known that some of these chemicals can leach out during the
3. IMPACT OF NANOPLASTICS ON HUMAN HEALTH product life cycle into the environment, leading to endocrine
Exposure to nanoplastic might occur via oral inhalation, disruption or acute toxicity when exposure to organisms
ingestion, or absorption by the skin in connection with the use occur.108 The same considerations apply for the monomers
of plastic products or unintentional means (Figure 3). (i.e., the chemical building blocks) used to manufacture the
Inhalation is likely to be relevant in occupational exposure polymers in the first place (of which small amounts may
1752 DOI: 10.1021/acs.est.8b05512
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Environmental Science & Technology Critical Review

remain in the polymers) and the products formed by the plastic fibers in indoor and outdoor air. Two private
chemical degradation of polymers. The most prominent apartments and one office were chosen as indoor sites,
example of a leaching monomer is bisphenol A (BPA), where a concentration between 1.0 and 60.0 fibers/m3 was
which is used for the preparation of polycarbonate and certain measured, which was significantly higher than the outdoor
epoxy resins. It has been shown that BPA causes adverse effects concentration (between 0.3 and 1.5 fibers/m3). Around 33% of
in humans due to its estrogenic activity, including several the fibers they collected indoors were of petrochemicals origin
metabolic diseases as well as reproductive and developmental with polypropylene being predominant, while the resting 67%
effects.109−111 In particular, polycarbonate drinking bottles consisted mainly of cellulose.124 However, there are thus far no
used for newborns showed high leaching of BPA. Newborns data available concerning the number or concentration of
have a much higher risk than adults since a higher internal aerosolized nanoplastics. The numbers presented by the
body burden is expected, expressed as concentration in blood/ studies of Dris et al. are more than 1000 times lower than
plasma, due to increased absorption or decreased elimination the permissible exposure maximum of 5 mg/m3 respirable
compared to the internal body burden of adults.112 nuisance dust/(8 h working day) established by the U.S.
3.1. Entry Routes of Nanoplastics into the Human Occupational Safety and Health Administration (OSHA).125
Body. Three major exposure pathways to nanoplastics are This suggests that the concentrations of microplastics found in
possible, i.e., via the lung, the gastrointestinal (GI) tract, and the air in these studies might be too low to have an adverse
the skin. The lung has a very large alveolar surface area of ca. effect on human health. Nevertheless, more data are needed, in
150 m2, with a very thin tissue barrier of less than 1 μm,113 particular taking into account the physicochemical character-
allowing nanosized particles to penetrate into the capillary istics of the material as well as their sizes.
blood system and to distribute throughout the human Furthermore, Wright and Kelly suggest that human exposure
body.114,115 Several studies have shown that exposure to to micro- and nanoplastics through inhalation might occur by
synthetic polymers can have an adverse effect on the health if the transportation of sea salt aerosols. These aerosols can arise
absorbed by the respiratory system.116−118 Studies applying from wave action containing polymer particles of appropriate
polystyrene particles to alveolar epithelial cells in vitro have sizes, which then can be transported by the wind to coastal
shown that nanoplastic particles are taken up and that the environments. Another scenario involves the application of
uptake rate is size-dependent (Figure 4).119−122 Recently, wastewater treatment sludge containing plastic particles to
agricultural land as a fertilizer. Once the sludge is dried, wind
can further transport the plastic particles and distribute them.
For further information regarding inhalation exposure of
microplastics, we refer readers to Wright and Kelly,50 Gasperi
et al.,126 and Prata,97 who provide detailed overviews of the
topic.
Although the concentration of synthetic polymer particles in
the air is usually very low, the GI tract, with its large surface
area of ca. 200 m2, represents the primary exposure site for
plastic particle uptake. Ingestion and accumulation of nano-
plastic particles in the GI tract has been demonstrated in a
wide range of aquatic organisms, such as fish, mussels, and also
birds.89,98,127−129 Human uptake of plastics might occur by
intentional swallowing, leading in the worst case to a plastic
bezoar,130 a rare cause of GI obstruction occurring mainly in
people with psychiatric ailments or, more likely, unintention-
ally via the food chain by the consumption of plastic-
contaminated food and drinks or possibly through migration
of nanoplastic particles from the packaging materials into food
products.
Figure 4. Human lung epithelial cancer cells (A549) labeled for F- It has been shown that microplastics ingested by fish are
actin (purple) and the nuclei (blue) showing uptake of 200 nm poorly absorbed via the GI barrier into the tissue, and gutting
amino-modified polystyrene particles labeled with FITC (yellow) of the fish reduces the possibility of consuming microplastic
after exposure for 24 h.
particles. In contrast, polystyrene nanoparticles have been
shown to overcome the GI barrier and to translocate into the
synthetic fibers in atmospheric fallout in urban areas have been underlying tissue, as demonstrated by several groups with filter
highlighted as a possible source for human exposure to feeders and shellfish.76,88,128 Data on the release of nano-
microplastics by inhalation.123 Atmospheric fallout of micro- plastics from packaging released into food products are
plastics, collected with a stainless steel funnel, was investigated currently unavailable; therefore, the exposure to humans
in two different urban and suburban sites in Paris. About 30% cannot be estimated for this method of intake.131
of particles observed were synthetic fibers with diameters Most of our current knowledge regarding nanoplastic and
between 7 and 15 μm and predominant sizes of 200−600 μm. intestine interaction comes from cell culture studies using
Between 2 and 355 particles/m2/day, with an average of 110 ± intestine cells. Several in vitro studies have investigated the
96 particles/m2/day were observed. Fluxes were found to be internalization and translocation of polystyrene nanoparticles
systemically higher at the urban site than at the suburban site. in intestine cell monocultures or even more complex human
Rainfall was also shown to have a clear effect on the intestinal cell models. Forte et al. showed that polystyrene
concentrations observed.123 Dris et al. investigated micro- nanoparticles with a diameter of 44 nm accumulate faster and
1753 DOI: 10.1021/acs.est.8b05512
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more efficiently in the cytoplasm of human gastric

adenocarcinoma cells than otherwise identical particles with
a diameter of 100 nm. In addition, the 44 nm particles showed
a strong upregulation of the interleukin (IL)-6 and IL-8 genes,
which are involved in gastric pathologies.132 Walczak et al.
determined the translocation of polystyrene particles with
diameters of 50 and 100 nm, having positively and negatively
charged as well as uncharged surfaces, in three in vitro intestine
cell models of increasing complexity using Caco-2, HT29-
MTX, and M-cells. Their results showed that both the size and
the chemical composition of the particle surface impacts their
translocation. The size clearly affected the translocation of the
nanoparticles, ranging up to 7.8% for the 50 nm and 0.8% for
the 100 nm particles. However, the surface chemistry seems
more important, as the two types of negatively charged 50 nm
NPs had a greater than 30-fold difference in translocation
rates.133 Mahler et al. suggested that acute oral exposure of
positively charged polystyrene nanoparticles can disrupt
intestinal iron transport and cellular uptake.134
The cellular uptake of nanoparticles is strongly influenced by
Figure 5. Transmission electron microscopy image showing
their interactions with surrounding biological components, commercially available spherically shaped polystyrene nanoparticles
such as proteins, phospholipids, or carbohydrates, due to their used for in vitro studies.
size, surface chemistry, and charge.135 Adsorption of proteins
from body fluids on nanoparticle surfaces results in the
formation of a so-called “protein corona” around the whereas neither particle type was found to penetrate into
particle.136 Hence, interactions between organs and tissue deeper skin tissue, possibly due to the barrier properties of the
generally occur with protein-coatedrather than bare stratum corneum. These results were confirmed by an
nanoparticles, likely causing changes in the characteristics additional study conducted by Campbell et al. a few years
and properties of the nanoparticle. Polystyrene nanoparticles later, who observed that polystyrene particles with diameters of
have been shown to form protein corona complexes in in vitro 20−200 nm penetrate only into the surface layers, approx-
GI studies, resulting in increased translocation,137 the change imately 2−3 μm, of the stratum corneum.142 A study
of the protein corona composition over time depending on the conducted by Vogt et al. identified fluorescent polystyrene
local environment,138 and increased cellular uptake and nanoparticles of a diameter of 40 nm in the perifollicular tissue
toxicity.139 Furthermore, the protein corona caused the of human skin explants pretreated with cyanoacrylate follicular
polystyrene nanoparticles to be retained in the gut. stripping and confirmed uptake by Langerhans cells after
In conclusion, it has been shown that, in contrast to transcutaneous application to human skin.143 Microbeads used
microplastic particles, nanoplastic particles overcome the GI in cosmetics such as scrubs and shampoos are processed by
barrier in aquatic organisms and can translocate into the mechanical means that may lead to their fragmentation into
underlying tissue. In addition, polystyrene nanoparticles can potentially more hazardous nanoplastics. In a recent
translocate the human intestine barrier in vitro. However, the publication, Hernandez et al. tested facial scrubs containing
reported studies rely solely on model polystyrene nanoparticles polyethylene microbeads with diameters of 200 μm for the
and are not from environmental samples (Figure 5). Other presence of nanoplastics. Scanning electron microscopy data
polymers such as PP, PE, and PET are, however, the main revealed nanoparticles ranging in size from 24 ± 6 to 52 ± 14
polymer material present in the environment. Thus, extrap- nm. The material composition was tested by X-ray photo-
olations of findings from polystyrene materials to other electron spectroscopy and Fourier transform infrared spec-
polymers should be made with caution, and new model troscopy, which confirmed that the identified nanoparticles
studies should be introduced including PP, PE, and PET. consisted of polyethylene.67 The further potential ability of
The skin forms a protective barrier against external nanoplastics to overcome the skin barrier can be extrapolated
influences such as physical injuries, chemical agents, or from data available from studies using nanoparticles. Skin
bacteria. Contact of plastics with the skin might occur via stress evoked by UV radiation has a widespread effect on the
the use of cosmetic products containing nanoplastic particles integrity of the skin barrier. An initial in vivo study conducted
or with nanoplastic-contaminated water. The stratum corneum by Mortensen and colleagues investigated nanoparticle skin
is the physical barrier of the skin, and due to the hydrophobic penetration of carboxylated quantum dots (QDs) with and
properties of the plastic particles, significant nanoplastic uptake without UV exposure. Their results showed qualitatively higher
through human skin in water is not to be expected. However, levels of penetration of QD nanoparticles in the UV exposed
possible entry routes include hair follicles, exits of sweat glands, mice, due to the perturbed expression of tight-junction-related
or via injured skin areas.140 Skin penetration and resulting proteins (Zonula occludens-1, claudin-1, and occludin), which
tissue distribution of plastics has been studied by Alvarez- promote intercellular adhesion.144 The effect that common
Roman et al., who applied fluorescent polystyrene particles commercial skin care lotions may have on the penetration of
with diameters of 20 and 200 nm to a porcine skin tissue QD nanoparticles into the skin was determined by Jatana et al.
model.141 Confocal laser scanning microscopy images revealed In their study, QDs were added to five commercial skin lotions
a higher accumulation of the 20 nm polystyrene nanoparticles and applied to freshly excised human skin as well as C57BL/6
than with the 200 nm sized particles in the follicular openings, hairless mice. Their findings suggest that certain ingredients
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Environmental Science & Technology Critical Review

(e.g., urea, glycerol, and α-hydroxyl acids) found in common endocytosis, have been described.155−157 Not all of the studies
commercial skin care lotions can enhance NP penetration into we present here have been performed with intestine cells;
the skin.145 In addition, several chemical penetration enhancers however, our aim is to provide an overview of the current
have shown their potential to support skin penetration by knowledge of polystyrene nanoparticles interaction with
nanoparticles.146 Kuo et al. illustrated the differences between human cells.
oleic acid, ethanol, and oleic acid−ethanol enhancers for the The first interaction of nanoparticles with cells is the
transport of zinc oxide nanoparticles. The results showed that interaction with the outer cell membrane. Rossi et al.
all three were capable of enhancing the transdermal delivery of investigated the interaction of polystyrene particles with
zinc oxide nanoparticles.147 However, there is currently little biological membranes by coarse-grained molecular simulations,
evidence that polymeric nanoparticles larger than 100 nm can which revealed that nanosized polystyrene particles can
penetrate into intact skin.148 permeate easily into lipid bilayer membranes, alter the
Once the plastic particles have entered the human body, membrane structure, and reduce molecular diffusion, thereby
they may overcome the primary tissue barriers and be affecting possible cell functions.158 Fiorentino et al. inves-
transported through the bloodstream to secondary organs. In tigated cellular uptake of 44 nm polystyrene particles on
vitro studies have shown that carboxylated polystyrene human colon fibroblasts and bovine oviductal epithelial
nanoparticles can adsorb to, and penetrate into, red blood cells.159 By way of uptake inhibition studies, they demonstrated
cells (RBCs) as a result of van der Waals, electrostatic, that the polystyrene nanoparticles were internalized mainly via
hydrogen bonding, and hydrophobic forces between poly- a clathrin-independent uptake mechanism. dos Santos et al.
styrene and the RBCs.149,150 This so-called cellular hitchhiking studied the effects of transport inhibitors on the cellular uptake
mechanism allows the polystyrene nanoparticles to avoid rapid of 40 and 200 nm carboxylated polystyrene nanoparticles in
clearance by the liver and spleen and, therefore, increase their human cervical HeLa cells, human glial astrocytoma 1321N1,
circulation time. and human lung epithelial A549 cell lines.160 The results
Secondary barriers able to be reached via the bloodstream clearly indicated that in all cases polystyrene nanoparticles
include the placental barrier and the blood−brain barrier entered the cells via active energy-dependent processes.
(BBB). Grafmueller and colleagues showed with an ex vivo However, since none of the transport inhibitors could fully
human placental perfusion model that polystyrene particles inhibit polystyrene uptake, the possibility remains that one cell
with diameters of up to 240 nm can be taken up by cells of the line uses multiple uptake pathways simultaneously.
placental barrier and transported from the fetal to the maternal RBCs are highly specialized cells distinguished by their lack
blood circulation.151 The operating translocation mechanism of a cell nucleus and endocytotic uptake mechanism. Studies
seems likely to be an energy-dependent transport pathway. The have been conducted in order to demonstrate cellular uptake
BBB is a highly selective barrier regulating the uncontrolled of different nanoparticles by RBCs and to better understand
diffusion of molecules into the brain. However, Yang et al. the operative uptake mechanism.161,162 Rothen-Rutishauser et
demonstrated BBB permeability with polystyrene nanoparticles al. showed uptake of nanosized polystyrene particles (diameter
having a diameter of 20 nm using an in vivo rat model by < 200 nm) by RBCs.163 This result indicated neither an
implantation of a microdialysis probe into the cerebral cortex endocytotic nor an actin-based uptake mechanism, therefore
of anesthetized rats injected with fluorescent polystyrene suggesting a passive diffusion mechanism for this specific cell
nanoparticles.152 A recent study by Rafiee et al. attempted to type.
assess the neurobehavior of rats exposed to pristine polystyrene However, it is important to mention that the uptake routes
nanoparticles upon oral exposure. They investigated different are not only size- and surface-chemistry-dependent but also
concentrations of 25 and 50 nm polystyrene particles (1, 3, 6, cell-type-specific. The same material can show different cellular
and 10 mg of polystyrene nanoparticles/(kg of body weight)/ uptake pathways: for example, polystyrene nanoparticles with a
day) administrated orally with adult male Wistar rats for 5 diameter of 120 nm, which surface had been modified to
weeks. No statistically significant behavioral effects were feature amidine groups, have been shown to be taken up by rat
observed in any of the tests performed.153 alveolar epithelial monolayers via non-endocytic mechanisms,
In conclusion, it has been shown by in vitro and in vivo in contrast to MDCK-II cells, which show particle uptake in an
studies that micro- as well as nanoplastic particles might be energy-dependent manner.121,164 Kuhn et al. showed that a
taken up into the human body and can overcome tissue combination of several distinguishable endocytotic uptake
barriers, thus also allowing interaction with single cells. mechanisms is involved in the uptake of 40 nm carboxylated
However, real-world plastics sources (rather than commercially polystyrene nanoparticles by macrophages and epithelial cells.
available perfectly spherical polystyrene particles) have not yet Selected endocytotic pathway inhibitors were applied, and it
been used; therefore, further studies applying different plastic was revealed in the case of J774A.1 macrophages that
materials with significant size and/or shape polydispersity as macropinocytosis, phagocytosis, and clathrin-mediated endo-
well as environmentally relevant concentrations need to be cytosis pathways are involved, whereas for human alveolar
conducted to fill the existing knowledge gaps. epithelial cells (A549), the uptake was dependent on caveolin-
3.2. Cellular Uptake Routes and the Intracellular Fate and clathrin-mediated endocytosis pathways.165 Nonvesicular
of Nanoplastic Particles. There are several pathways by transport through the membrane might allow the nanoplastic
which nanoparticles can be taken up by cells.154 Although particles to interact directly with intracellular molecules or to
passive diffusion through the cell membrane (also referred to release their payload, such as POPs, directly into the
as adhesive interaction), channel- or transport-protein- cytoplasm. This might lead to accumulation of POPs in the
mediated uptake have been described, endocytotic nano- cell and potential toxicological effects on the human body.166
particle uptake is the major mechanism of cells. A range of Endocytosis of plastic particles will follow the intracellular
endocytotic pathways, including phagocytosis and macro- endocytotic pathway involving early and late endosomes
pinocytosis, as well as clathrin- and caveolae-mediated followed by fusion with lysosomes. Salvati et al.122 demon-
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Environmental Science & Technology Critical Review

strated the intracellular lysosomal localization of 40−50 nm nanoparticles. Application of 20 nm carboxylated polystyrene
polystyrene nanoparticles in A549 cells. These findings are in particles caused continuous short-circuit currents by the
agreement with other published data, which show accumu- activation of basolateral K+ channels and the stimulation of
lation of nanosized polystyrene particles in the lysosome, Cl− and HCO3− secretion. These findings underline that
whereas no lysosomal escape or even particle degradation was polystyrene nanoparticles may have the ability to affect the
observed under acidic conditions.167 epithelial cell function and physiological processes.173 Fuchs et
In another study, the importance of the physicochemical al. investigated the effect of 120 nm carboxylates and amino-
properties of mesoporous silica and polystyrene nanoparticles modified polystyrene particles on the polarization of human
were compared; the results revealed clear differences in cellular macrophages into M1 or M2 phenotype. Their observations
uptake mechanisms using ovarian cancer cells.168 It was shown revealed that the expression of the M1 markers CD86, NOS2,
that the two types of nanoparticles never showed an overlap in TNF-a, and IL-1b was not affected, while for M2 types both
their endocytotic uptake routes. Mesoporous silica particles nanoparticles impaired expression of scavenger receptors
entered the cells via caveola-mediated endocytosis and, CD163 and CD200R, and the release of IL-10. The amino-
depending on their size, resided within the lysosome (50 modified particles also inhibited the phagocytosis of Escherichia
nm) or were relocated in the cytoplasm (10 nm). Cellular coli by both, M1 and M2 macrophages, while the carboxylated
uptake of polystyrene nanoparticle occurred via a caveola- particles did not affect the phagocytosis of the bacteria by M2,
independent route. Amine-modified 50 nm polystyrene but increased protein mass in M1 and M2, TGF-b1 release by
particles were localized within the lysosome and showed M1, and ATP levels in M2.174
toxicity after 4−8 h in comparison to 30 nm carboxyl-modified A new strategy to develop efficient nanoparticle-based drug
polystyrene particles, which did not follow the classic acidic delivery systems involves the use of RBCs as a carrier system,
endocytotic pathway and were not toxic. It is well-known from which can increase the circulation of nanoparticles in vivo. In
the literature that a positive surface charge of nanoparticles this context, Barshtein et al. investigated RBCs with attached
often results in increased cytotoxicity and cellular uptake by polystyrene nanoparticles having diameters of 50, 108, and 243
unspecific binding to negatively charged sugar moieties on the nm, probing in particular the aggregation of RBCs and their
cell surface, whereas negatively charged particles impair adhesion to endothelial cells. The authors showed that the
endocytosis due to repulsive interactions.169,170 A variety of formation of RBC aggregates increased with decreasing particle
cellular uptake routes and intracellular localizations of size and in parallel a distinctly elevated adhesion to endothelial
polystyrene nanoparticles have been observed depending on cells was observed.175 In addition, Barbul et al. showed that
the physicochemical properties; however, there is a lack of polystyrene particles with sizes of 27, 45, and 100 nm adsorbed
specific quantitative data regarding cellular entry and the fate to RBCs led to shape transformations and reduced cell
of nanoplastics. deformability, with the 27 nm particles showing the strongest
It is obvious that size matters and plastic nanoparticles effect.176
interact differently with human cells in comparison with larger Furthermore, Xia et al. showed the influence of 30 nm
ones; however, the uptake is also dependent on the particle polystyrene nanoparticles on the endocytotic pathway in
charge which might influence the behavior in the cell culture macrophages and human cancer cell lines A549, HePG-2,
media. Since most of the in vitro studies described here have and HCT116. The particles induced the formation of large
used polystyrene particles, it is of course difficult to extrapolate vesicle-like structures, which blocked the vesicle transport in
the results to other kind of plastic particles and more research the endocytic system and the distributions of regular proteins
with other plastics is highly recommended. required in cytokinesis, which led to the formation of
3.3. Adverse Effects of Nanoplastics. Nanosized binucleated cells.177 A recent study by Inkielewicz-Stepniak
materials in general have raised concerns regarding possible et al. investigated the role of mucin in the toxicological impact
hazards and risks for the environment and especially for human of polystyrene nanoparticles. Their findings showed that
health. An understanding of possible human exposure is critical amine-modified 57 nm sized polystyrene particles have the
to determine health hazards. Adverse effects of nanoparticles in ability to strongly interact and aggregate mucin and induced
vivo include cytotoxicity, (pro-)inflammation, or production of apoptosis equally on mucin- and non-mucin-secreting
reactive oxygen species (ROS).171 A number of in vitro studies intestinal epithelial cells.178 Further studies using cationic
using human cell lines (Table 1) have revealed that polymer polystyrene nanoparticles indicated the increase in ROS
nanoparticles have the potential to activate the innate immune production and endoplasmatic reticulum stress caused by
system, inducing inflammatory responses, or mediating misfolded protein aggregation in macrophage (RAW 264.7)
oxidative stress. In in vitro experiments, Brown et al. showed and lung epithelial (BEAS-2B) cells, leading to autophagic cell
pro-inflammatory responses of polystyrene particles with death.179,180 A further study confirming that polystyrene
diameters of 202 and 535 nm upon exposure to human particles are able to induce ROS production was conducted
A549 lung cells, observing an increased IL-8 expression relative by Liu et al. In their study they showed that polystyrene
to that elucidated by polystyrene nanoparticles with a diameter particles 500 nm in size could stimulate ROS generation in
of 64 nm.172 As seen by Forte et al., unmodified polystyrene human liver cells.181
nanoparticles with a diameter of 44 nm induced a strong Aside from polystyrene, an in vitro study using unmodified
upregulation of IL-6 and IL-8 genes in experiments using polyethylene particles with sizes ranging from 0.3 to 10 μm
human gastric adenocarcinoma cells, indicating that the showed unequivocally that the plastic particles stimulated
induction of pro-inflammatory responses by polystyrene does mice-derived macrophages to produce significant levels of
not necessarily have to be charge-driven (as suggested by many cytokines such as IL-6, IL-1β, and TNF-α.182 Furthermore,
studies) but may instead be a material-based or simple particle several studies of human patients have shown that normal
occurrence issue.132 McCarthy et al. identified the activation of usage of implants such as total joint replacements made of
ion channels in human lung cells after exposure to polystyrene polyethylene can lead to the production of wear debris.183−185
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 Table 1. Overview of in Vitro Studies Using Human Cell Lines Demonstrating Cellular Uptake and Effects upon Exposure to Polystyrene Nanoparticles
material, modification size, nm major findings target/cell line ref
polystyrene, unmodified 44 induced strong up-regulation of IL-6 and IL-8 human gastric adenocarcinoma cells (AGS) Forte et al.132
genes
polystyrene, 50, 100 size dependency regarding particle translocation human colon carcinoma cells (Caco-2), Walczak et al.133
unmodified, carboxylated, amino-functionalized human colon adenocarcinoma cells (HT29-MTX),
human intestine microfold cells
polystyrene, carboxylated 44 maximum particle uptake after 30 min human colon fibroblasts (HCF) Fiorentino et al.159
polystyrene, carboxylated, amino-functionalized 50, 200 disruption of iron transport due to polystyrene human colon carcinoma cells (Caco-2), Mahler et al.134
particle exposure human colon adenocarcinoma cells (HT29-MTX)
polystyrene, carboxylated, amino-functionalized 20, 40 higher uptake efficiency of carboxylated particles human colon carcinoma cells (Caco-2) Thubagerre and Reinhard190
compared to amino-funtionalized particles,
induction of apoptosis
polystyrene, amino-functionalized 57 binding of mucin and induction of adoptosis human colon carcinoma cells (Caco-2, LS174T, HAT-29) Inkielewicz-Stepniak et al.178
polystyrene, carboxylated 20, 40, 100 40 nm particles internalized faster than human lung carcinoma cells (A549), Varela et al.119
20 or 100 nm particles in both cell lines human astrocytoma 1321N1
Environmental Science & Technology

polystyrene, carboxylated 116 cellular uptake human lung carcinoma cells (A549) Deville et al.120
polystyrene, carboxylated 40−50 cellular uptake irreversible, intracellular concen- human lung carcinoma cells (A549) Salvati et al.122
tration increased linearly
polystyrene, n.d.a. 64, 202, 535 increased IL-8 expression for 202 and 535 nm human lung adenocarcinoma cells (A549) Brown et al.172
particles compared to 64 nm
polystyrene, carboxylated 20 activation of ion transport human lung adenocarcinoma (Calu-3) McCarthy et al.173
polystyrene, 60 amino-functionalized polystyrene particles induce human bronchial epithelium (BEAS-2B), Chiu et al.179
unmodified, carboxylated, amino-functionalized autophagic cell death through the induction of mouse monocyte macrophage (RAW 264.7)
endoplasmic reticulum stress
polystyrene, 60 amino-functionalized particles induced mitochon- human bronchial epithelium (BEAS-2B), Xia et al.180

1757
unmodified, carboxylated, amino-functionalized drial changes leading to cell death mouse monocyte macrophage (RAW 264.7)
polystyrene, 50, 100 amine-modified particle-induced oxidative stress, human immortalized alveolar epithelial type 1 cells (TT1), Ruenraroengsak and Tetley191
unmodified, carboxylated, amino-functionalized mitochondrial disruption and release of primary human alveolar macrophages (MAC),
cytochrome C, indicating apoptotic cell death primary human alveolar type 2 (AT2) epithelial cells
polystyrene, 50 particles partly adsorbed and internalized, then human Calu-3 epithelial cells, Paget et al.192
unmodified, carboxylated, amino-functionalized released by Calu-3 cells, while human monocytic leukemia cell line THP-1
THP-1 macrophages quickly incorporated all
particles, aminated polystyrene nanobeads were
more cytotoxic and genotoxic than unmodified
and carboxylated ones
polystyrene, carboxylated, amino-functionalized 100 concentration of internalized nanoparticles, their human monocytic leukemia cell line THP-1, macrophages Lunov et al.193
uptake kinetics, and mechanism may differ
considerably between primary cells and a related
tumor cell line
polystyrene, carboxylated 20, 100, 200, 500, 1000 20 nm particles were taken up passively, human monocytic leukemia cell line THP-1, Prietl et al.194
100−1000 nm actively and passively, 20 nm human histocytic lymphoma cells U937
stimulated IL-8 secretion in human monocytes
and induced oxidative burst, 500 and 1000 nm
particles stimulated IL-6 and IL-8 secretion in
monocytes and macrophages
polystyrene, carboxylated, amino-functionalized 120 both particle types impaired expression of scav- human monocyte macrophages Fuchs et al.174
enger receptor CD163 and CD200R, and the
release of IL-10
polystyrene, unmodified n.d.a. 20, 100, 200, 500, 1000, 2000 cellular uptake pathway of polystyrene particles is bone-marrow-derived macrophages (BMDM), fibroblast L929, Firdessa et al.195
cell-line-dependent kidney epithelial cells 293T
polystyrene, carboxylated 44 maximum particle uptake after 1 h human renal epithelial cells (HRCE) Monti et al.196
polystyrene, carboxylated, amino-functionalized 110 cellular uptake human microvascular endothelial cells (ISO-HAS1), Tenzer et al.138
Critical Review

human umbilical vein endothelial cells

Environ. Sci. Technol. 2019, 53, 1748−1765

DOI: 10.1021/acs.est.8b05512
Environmental Science & Technology Critical Review

Wear debris polyethylene particles seem to trigger the release

of pro-inflammatory factors, such as TNF-α, IL-1, and pro-
osteoclastic factors such as receptor activator of NF-κB ligand
(RANKL), resulting in periprosthetic bone resorption
Maneerat et al.168

Johnston et al.197
(osteolysis) and, in the worst case, eventual loss of the
ref

Zauner et al.198

Kang et al.200
implant.186 As illustrated by Devane et al., the tissue around

Jiang et al.199
Liu et al.181
ultrahigh molecular weight polyethylene-based prostheses
often contains large numbers of small particles with sizes
ranging from 0.2 to 10 μm, and macrophages have been
frequently observed, confirming the recruitment of the innate

human head and neck squamous cancer cells (HNX 14C),

immune system.187 Shanbhag et al. analyzed the composition
and morphology of wear debris from interfacial membranes of

human embryonic kidney epithelial cells (HEK293T),

human pancreatic adenocarcinoma cells (PANC-1),
failed total hip replacements. Their findings revealed that most
human ovarian carcinoma cells (NIH-OVCAR-3)

human colorectal adenocarcinoma cells (HT29),

of the particles found were polyethylene and had a mean size
human hepatocyte carcinoma cells (HepG2),
human hepatocyte carcinoma cells (HepG2),

of around 530 nm.188 To overcome the observed negative

human lung adenocarcinoma cells (A549)

human bladder carcinoma cells (ECV 304),
human ovarian carcinoma cells (SKOV-3),

human vein endothelial cells (HUVEC)

effects, surgeons are now increasingly using metal-on-metal

target/cell line

human hepatoblastoma cells (C3A)

joint replacements.
Furthermore, the production of fluorescein labeled poly-
ethylene terephthalate (PET) nanoparticles was recently
human liver cells (Huh 7)

shown by Magri et al.189 In their study, they present a top-

mesenchymal stem cells

down approach based on laser ablation of polymers to form

PET nanoparticles with weak acid groups on their surface,
which should mimic real environmental nanopollutants. In
vitro studies using human intestinal epithelial cells (Caco-2)
showed internalization and biopersistance as well as long-term
stability in a simulated lysosomal environment. In addition,
cells treated with nano-PET particles did not increase ROS
50 nm positively charged PS particles accumulated

uptake of particles by hepatocytes was size-, time-,

polystyrene particles could stimulate O2̇generation

HUVEC, ECV 304, and HNX 14C show particle

uptake up to 1010 nm; HepG2 did not take up

increased cellular uptake of particles under fluidic

generation over 96 h, and no cytotoxicity was detectable.

20 nm particles taken up avidly by all cell lines;

carboxylated particles internalized more rapidly

negatively charged particles, cellular uptake

particles was limited, but 20 nm NPs were

However, as suggested by the authors, possible long-term

within lysosome in comparison to 30 nm

and serum-dependent, uptake of 200 nm

effects in cells or tissue cannot be excluded and need to be

evaluated further.
and showed higher accumulation

In conclusion, it has been shown by in vitro and in vivo data

major findings

internalized by both cell types

that nanosized plastic particles can induce the activation of cell

particles larger than 93 nm

responses, especially effects on the immune system. However,

caveolae-independent

long-term studies with repeated exposures are absent, as well as

thorough material testing, including plastics such as PE, PET,
and PP, since most of the current studies are performed with
shear stress

polystyrene particles. Furthermore, it is important to fill the

knowledge gap between environmental relevant concentrations
and the concentrations found in the organisms/cells to carry
out relevant studies on the impact on human health.

4. DETECTION OF NANOPLASTICS
20, 93, 220, 560, 1010

The reliable detection of polymer-based nanoparticles in

size, nm

environmental samples or complex biological matrices is highly

challenging, due to their small size and the fact that their
30, 50, 1000

overall chemical composition is not all too different from that

20, 200

of organic matter. The detection of nanoplastic particles

500

110

100

according to their size is not sufficient, as additional chemical

characterization is needed for identification of the particles. To
polystyrene, carboxylated, amino-functionalized

the best of our knowledge, only one study has so far been
published showing the detection and chemical analysis of
nanoplastics in an environmental sample. Ter Halle et al.
collected water samples from the North Atlantic Subtropical
material, modification

polystyrene, amino-functionalized

Gyre, and after ultrafiltration of the water, they used dynamic

n.d.a. = no data available

light scattering to prove the presence of nanoparticles. To

Table 1. continued

polystyrene, carboxylated

polystyrene, carboxylated

evaluate the chemical identity of the particles, they conducted

polystyrene, unmodified

pyrolysis coupled with gas chromatography−mass spectrome-

polystyrene n.d.a.

try. They estimated that the colloidal fraction signal of

seawater could be attributed on average to a mixture of 73%
PVC (±18%), 18% PET (±16%), and 9% PS (±10%). In
addition, they observed changes in the pyrolytic signals of
polyethylene with decreasing debris size, concluding that this
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Environmental Science & Technology Critical Review

could be related to the structural modification of this plastic as organisms and humans is limited, and several important
a consequence of weathering processes.201 questions for future studies remain such as the following: What
A promising possible method for the detection and chemical is the concentration of nanoplastics in the water? Can this
characterization of nanoplastic particles in complex matrices is concentration impact the aquatic system and, thus the food
hyperspectral imaging technology. Hyperspectral imaging is a chain, resulting in potential hazardous effects for humans? Can
recently established technique that quantifies the reflectance we confirm the occurrence of nanoplastic in the human food
intensity of microscopic samples in the UV−vis range (400− chain to determine the potential exposure to humans? Given
1000 nm) to generate spectra specific to a material at pixel these unsolved questions, new technological approaches and
resolution.202,203 Hyperspectral imaging has proven to be methods are needed for the detection of nanoplastic particles
suitable for the detection and characterization of microplastic in the environment and in organisms.
samples from ocean samples as well as from soil.204,205 Shan et In addition, it is not known to what extent nanoplastic can
al. investigated the effects of particle size and color of be further degraded after ingestion, for example under the
micoplastics found in soil. The results showed that white PE acidic conditions found in the gut or inside the cells in the
could be detected with the precisions of 84% and 77% for PE digestive organelles, i.e., the lysosomes. It is also unclear
particles in size ranges of 1−5 mm and 0.5−1 mm, whether nanoplastic can overcome the gut−intestine epithelial
respectively, while the precision of black PE in the same size barrier or if they are restricted to the gut lumen. Another
ranges were found to be 58% and 76%, respectively. interesting question is to what extent the ingestion of
Furthermore, Mattsson et al. demonstrated the use of nanoplastic can promote the uptake of chemical hitchhikers
hyperspectral imaging for the detection of polystyrene and the possible leaching of chemicals from the plastic material
nanoparticles with a diameter of 52 nm within the brain tissue that could cause harm to the human body. In addition, plastic
of fish. The brains were homogenized and polystyrene was particles appear in numerous types, shapes, and sizes, with or
spectrally mapped and identified in the exposed brain images without associated chemicals. Inconsistent use of units,
using the Spectral Angle Mapper algorithm.90 exposure media, and habitats makes it even more difficult to
Methods used to characterize nanoparticles in general such combine exposure and effect data in a significant character-
as UV−vis spectrometry, electron microscopy, field flow ization of the risks. This turns the development of a rational
fractionation (FFF), or dynamic light scattering (DLS) risk assessment framework for plastic into a very challenging
techniques have also been suggested to be suitable for task.68 Unfortunately, it stands to reason that many aspects in
nanoplastics. However, these methods need to be combined the context of environmental polymer nanoparticles cannot be
to achieve the chemical confirmation of the identity of the generalized. There is therefore a need to establish data for the
material, as this is often lacking as seen by Correia et al.206 different plastic materials found in the environment. While the
New approaches might involve the introduction of nano-FTIR most commercially most relevant polymers are polyolefins
absorption spectroscopy and Raman spectroscopy as well as (notably different types of polyethylenes and polypropylene),
combined atomic force microscopy and infrared spectroscopy polyesters, and polyurethanes, most of the studies conducted
(AFM-IR), which all show the capabilities in the area of with polymer nanoparticles were carried out with polystyrene,
nanoscale chemical characterization.207−209 as this material is commercially available and inexpensive and
In conclusion, there is still a lack of reliable methods to can also be easily synthesized and processed into nanoparticles.
detect nanoplastic particles in combination with reliable Therefore, we propose that focus should be placed on
chemical characterization in environmental samples and/or comprehensive studies using diverse plastic materials at
complex biological matrices. relevant concentrations, as well as modeling chronic exposure,
for a more realistic hazard and risk assessment. Future research
5. CONCLUSIONS AND FUTURE PERSPECTIVES should also move toward the terrestrial environment, about
Polymers represent one of the most important materials which even less is known. Studies involving terrestrial, but also
families of the 21st century, as they are used practically freshwater eco-systems will be very supportive for the overall
everywhere and strongly influence our daily lives in many understanding of the micro- and nanoplastic pollution in the
different ways. At the same time, these materials as a whole are environment and its possible impact on human health.37
also one of the largest sources of environmental pollution that
mankind is exposed to. Recent studies have presented evidence
that the process of plastic degradation also results in the
■ AUTHOR INFORMATION
Corresponding Author
formation of nanoplastic with physicochemical characteristics *Phone: +41 26 300 9502; E-mail: [email protected].
different from the corresponding bulk materials. An increasing
body of knowledge has shown that nanoplastics have adverse ORCID
effects on aquatic species, but in contrast to microplastics, Roman Lehner: 0000-0002-0478-5445
nanoplastics can overcome the intestine tissue in aquatic Christoph Weder: 0000-0001-7183-1790
systems and therefore possibly end up in the human food Alke Petri-Fink: 0000-0003-3952-7849
chain. Thus, it appears important to accelerate the inves- Notes
tigation of the presence and fate of nanoplastics in the
The authors declare no competing financial interest.

■
(aquatic) environment. In addition to studies addressing the
effects of nanoplastics on aquatic organisms, exposure risks for
humans via the food chain should be explored in more detail as ACKNOWLEDGMENTS
in vitro studies using human cell lines showed evidence that This work was supported by the Adolphe Merkle Foundation
polystyrene nanoparticles are taken up and induce oxidative and the Grant No. 310030_159847/1 to B.R.-R. We thank Dr.
stress or pro-inflammatory responses. Furthermore, informa- Miguel Spuch for the illustrational work of the TOC art
tion on the long-term fate of ingested nanoplastics in aquatic graphic and Figure 3.
1759 DOI: 10.1021/acs.est.8b05512
Environ. Sci. Technol. 2019, 53, 1748−1765
Environmental Science & Technology Critical Review

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1765 DOI: 10.1021/acs.est.8b05512

Environ. Sci. Technol. 2019, 53, 1748−1765