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Table 1 Overview of the literature investigating neurotoxic effects of micro- and nanoplastics. The particle concentration is only mentioned for micro- and nanoplastics or for mixtures containing micro- and nanoplastics. The reported particle size reflects the diameter of primary particles. Every study included a control group that was not exposed to micro- and nanoplastics or any other substance, or measurements were taken at timepoint 0, before exposure

From: The plastic brain: neurotoxicity of micro- and nanoplastics

Model systemParticle type / sizeExposure methodExposure dose(Neuro)toxic effectsRef.
Nematodes
Caenorhabditis elegansPS-MPs of 0.1, 0.5, 1, 2 & 5 μmin medium, for 3 days1 mg/L mediumExcitatory toxicity on locomotive behaviour. Damage to cholinergic and GABAergic neurons, oxidative stress; no clear size-dependence).[69]
 Earthworm (Eisenia fetida)PE-MPs of 100–200 μmin soil, for 7–28 days0.1, 0.25, 0.5, 1.0 and 1.5 g/kg soilParticle ingestion at 1.5 g/kg. Skin damage (1.5 g/kg). Increased AChE activity (≥1.0 g/kg and 1.5 g/kg at respectively 21 and 28 days). Increased CAT activity and MDA levels (1.0 g/kg, 28 days).[70]
Bivalves
 Zebra mussel (Dressene polymorpha)PS-MPs mixture of 1 & 10 μm (1:1)In water, for 3 & 6 days1 × 106 MPs/L (mix 1)
4 × 106 MPs/L (mix 2)
Particle presence in hemolymph and tissues. Increased DA levels (mix 1, 3 days & mix 2, 6 days). Cellular stress (decreased CAT; mix 1, 6 days). No change in AChE or MAO activity or in Glu and 5-HT levels. No genotoxicity.[71]
 Peppery furrow shell (Scrobicularia plana)PS-MPs of 20 μmIn water, for 14 days followed by 7 days of depuration1 mg/L
(~ 4000 particles/L)
Particle presence in hemolymph, gills and digestive gland. Increased SOD (gills, ≥7 days exposure; digestive gland, ≥14 days). AChE and LPO activity decreased (gills, 3–14 days). CAT activity decreased (digestive gland, ≥3 days).[72]
 Mediterranean mussel (Mytilus galloprovincialis)PS-MPs of 0.11 μmIn water, for 96 h0.005, 0.05, 0.5, 5 and 50 mg/L MPs alone, and mixture of 0.05 mg/L PS-MPs + 6.3 μg/L CbzAltered gene expression (MPs alone and MPs with Cbz; ≥ 0.05 mg/L). ChE inhibition in hemolymph (MPs 0.05 and 0.5 mg/L). DNA damage (≥ 0.05 mg/L).[73]
 Mediterranean mussel (Mytilus galloprovincialis)PE-MPs and PS-MPs of 100 μmIn water, for 7 days1.5 g/L
(with and without 50 μg/L pyrene)
Particle presence in hemolymph, gills and gut. Reduction of AChE activity in gills (PE and PS). Nuclear alterations and DNA damage, but no changes in oxidative stress markers (GST, CAT, LPO).[74]
 Asian clam (Corbicula flumenia)MPs (Red Fluorescent Polymer Microspheres)*of 1–5 μmIn water, for 96 h0.2 mg/L (~ 37.000 particles/L) and 0.7 mg/L (~ 128.500 particles), with or without 1.8 mg/L and 7.1 mg/L Florfenicol (antimicrobial agent)Particle presence in gut, digestive gland lumen, connective tissue, hemolymphatic sinuses, and gills surface. Inhibition (31%) of ChE activity (0.2 mg/L, but not at 0.7 mg/L), which was exacerbated by Florfenicol.[75]
 Asian clam (Corbicula flumenia)MPs (Red Fluorescent Polymer Microspheres)*of 1–5 μmIn water, for 8 days0.13 mg/L (~ 24.000 particles/L), with or without 30 μg/L mercuryParticle presence in digestive tract and gills. Inhibition (15%) of ChE activity. Increased (~ 2-fold) LPO levels suggestive for
oxidative stress (LPO).
[76]
Crustaceans
 Striped barnacle (Amphibalanu ampitrite)PS-MPs (fluorescent) of 0.1 μmIn water, for 24 and 48 h0.001, 0.01, 0.1, 1, 10 mg/LParticle presence in gut. Decreased swimming speed (≥ 1 mg/L). Increase in ChE activity (0.001–0.1 mg/L). Decrease in (P)ChE activity (1 mg/L). Increase in CAT activity (0.1–1.0 mg/L).[77]
 Brine shrimp (Artemia fransiscana)PS-MPs (fluorescent) of 0.1 μmIn water, for 24 and 48 h0.001, 0.01, 0.1, 1, 10 mg/LParticle presence in gut. Increased swimming speed (≥ 1 mg/L). Decrease in AChE activity (0.001–0.01 mg/L). Increase in PChE activity (0.01–0.1 mg/L). Increase in CAT activity (0.001–1.0 mg/L).[77]
 Brine shrimp (Artemia fransiscana)PS-NH2 NPs of 50 nmIn water, for 48 h up to 14 days0.1, 1.0, 3.0 and 10.0 mg/LChE activity decreased (1 mg/L). CbE activity decreased (1 mg/L). GST decreased (1 mg/L). CAT decreased (1 mg/L).[78]
Fish
 Japanese rice fish (Oryzias latipes)PS-NPs of 40 nmIn medium, for 7 days10 mg/LParticle presence in gills, intestine, testis, liver, blood and brain, suggesting penetration of BBB.[79]
 Red tilapia (Oreochromis niloticus)PS-MPs of 0.1 μmIn medium, for 1–14 days1, 10 and 100 μg/LParticle presence in gut, gills, liver and brain tissue (≥ 1 μg/L, ≥ 6 days). Inhibition of AChE activity (37.7%) in brain (≥ 1 μg/L, ≥ 3 days). Antioxidant enzyme induction (SOD; ≥ 1 μg/L, 1 days > 3–14 days); no change in MDA levels.[80]
 Crucian carp (Carassius carassius)positively charged amino-modified PS-NP and -MP of 53 and 180 nmIn water, for 64 days or via PS-NP fed crustaceans100 mg/LParticle presence in brain (53 nm and 180 nm). brain weight loss (53 nm and 180 nm). Behavioural changes and enlarged cerebral gyri (53 nm).[22]
 Convict surgeonfish, juvenile (Acanthurus triostegus)PS-MPs of 90 μmIn water, for 8 days0.81 mg/L (~ 5000 particles/L)Particle presence in digestive tract. No effect on foraging behaviour, body weight or survival rate when exposed to a predator.[81]
 Zebrafish, juvenile (Danio rerio)PE-MPs of 10 μmIn water, for 10 and 20 days5, 50 and 500 μg/L (or 1040, 10,400 and 104,000 particles/L)Particle presence in intestine, but not in brain or other organs. No changes in growth or ache gene expression.[82]
 Zebrafish, adult (Danio rerio)PE-MPs of 10–22, 45–53, 90–106, 212–250 and 500–600 μmIn water, for 96 h11, 110, 1.100 MPs/LIngestion and particle presence in intestine and gills (19.7–558.4 μm). Altered locomotive behaviour (≥ 110 MPs/L) and induction of seizures (≥1100 MPs/L). No changes in mortality.[83]
 Discus fish (Symphysodon aequifasciatus)PE-MPs of 70–88 μmIn water, for 30 days (28 °C and 31 °C)200 μg/LParticle presence in body (31 °C > 28 °C). Decreased AChE in head (both 28 °C and 31 °C). No changes in growth or survival rate.[84]
 Zebrafish, larvae (Danio rerio)PS-NPs of 47 nm,
PS-MPs of 41 μm
In water, for 5 days1 mg/L, with or without 2 and 20 μg/L EE2Particle presence in body. Inhibition of AChE by 9% (MPs), 40% (NPs) 21% (MP and NP co-exposed with EE2); locomotor hypoactivity 22% (NPs) and 18–36% (co-exposed with EE2).[85]
 Zebrafish, larvae (Danio rerio)PS-NPs of 50 nmIn water, for 3 days1 mg/L, with or without 0.78 and 1.0 μg/L BPAParticle presence in head, gills and muscle. Decreased AChE activity 46% (NPs alone) and increased DA levels (only for mixture of PS-NP with BPA).[86]
 Barramundi, juvenile (Lates calcarifer)PS-MPs of 97 μmIn water, for 24 h100 MPs/L, with or without 100 nM PyreneLittle (co-exposure) or no (PS-MPs alone) effect on swimming movement or foraging behaviour.[87]
 Red tilapia (Oreochromis niloticus)PS-MPs of 0.1 μmIn water, for 1–14 days1, 10 and 100 μg/L, with 50 μg/L ROXParticle presence in gut, gills and to a lesser extent also brain and liver. Decrease in AChE activity (co-exposed, ≥ 1 μg/L). Note: there was no ‘MP only’ group.[88]
 Sea bass, juvenile (Dicentrarchus labraxMPs* of 1–5 μmIn water, for 96 h0.26 and 0.69 mg/L, with or without 10 and 16 μg/L mercuryInhibition of AChE activity (50%) and increased LPO in the brain (0.69 mg/L MPs). Inhibition of AChE (64–76%) and increased LPO in brain exacerbated by co-exposure (mercury, all concentrations).[16]
 Common goby, juvenile (Pomatoschistus microps)PE-MPs of 1–5 μmIn water, for 96 h0.216 mg/L, with or without 5.6–28.4 mg/L chromiumAChE activity decreased with 20% (MPs alone) and 31% (co-exposed with chromium).[89]
 Common goby, juvenile (Pomatoschistus microps)PE-MPs of 1–5 μmIn water, for 96 h0.18 mg/L, with or without 3–50 mg/L cadmiumIncreased mortality (MP alone and in mixture with Cd); decreased AChE activity (MP alone and mixture MP with 3, 6 and 13 mg/L); behavioural inhibition (MP alone and mixture MP with 3, 6 and 13 mg/L Cd); no oxidative stress (LPO and GST).[90]
 Common goby, juveline (Pomatoschistus microps)PE-MPs of 1–5 μmIn water, for 96 h18.4 μg/L and 0.18 mg/L, with or without
200 μg/L pyrene
Decrease in AChE activity (22%) (MP alone and co-exposed) (18.4 μg/L = 184 μg/L).[91]
 Common goby, juvenile (Pomatoschistus micropsPE-MPs of 1–5 μmIn water, for 96 h0.18 mg/L, with or without 0.2 mg/L Au0-NPInsignificant AChE activity inhibition (13%); oxidative stress (LPO, GST) (25 °C, not 20 °C).[92]
 Common goby, juveline (Pomatoschistus microps)PE-MPs of 1–5 μmIn water, for 96 h0.18 mg/L, with or without 1.3–10 mg/L cefalexinDecrease in AChE (8% at 20 °C, 21% at 25 °C), behavioural inhibition (28% at 25 °C) and mortality (33% 25 °C); mixture increased toxicity of MPs and cefalexin.[93]
Mammals
 Mouse (Mus musculus)PS-MPs of 5 μm and 20 μmOral gavage for 30 days0.01–0.5 mg/day
(~ 0.5–25 mg/kg body weight/day, assuming bodyweight of 20 g).
(1 × 105–5 × 106 5 μm particles / 2 × 103–1 × 105 20 μm particles)
Particle presence in gut, liver and kidney. In liver, dose-dependent increase in AChE, LDH, GSH-Px and SOD activity; dose-dependent decrease in ATP and CAT in liver (≥ 0.01 mg/day, both 5 and 20 μm).[94]
 Wistar rat, male (Rattus norvegicus domestica)PS-MPs of 40 nmOral gavage for 35 days1, 3, 6 and 10 mg/kg body weight/dayNo alterations in behaviour or body weight gain.[95]
Cell cultures
 Human-derived cerebral cell line (T98G) and epithelial cells (HeLa)PE-MPs of 3–16 μm,
PS-MPs of 10 μm
In culture medium, for 24 h0.05, 0.1, 1, 10 mg/LROS generation (PS only at 10 mg/L; both cell lines). No changes in cell viability.[96]
 Primary mouse astrocytes, neurons, microglia and brain vascular endothelial cellsPS-PEG and PS-COOH NPs of 55 nmIn culture medium, for 24 h7.8–250 mg/L
(or 3 × 1013 up to 1 × 1015 NPs/L)
Decreased mitochondrial activity and cell viability (≥ 250 mg/L). Internalization of NPs (2 × 1014 NPs/L).[97]
 Human-derived embryonic stem cell (3D model)PE-NPs of 33 nmIn culture medium, for 84 h and for 18 days22.5, 45, 90, 180, 360, 720 and 1440 mg/L (48 h),
22.5, 45, 90, 180, 360 mg/L (18 days)
48-h exposure: Penetration of NPs into 3D structure, internalization of NPs (≥ 360 mg/L). Increased cytotoxicity and oxidative stress (dose-dependent).
18-day exposure: PE-NP accumulation (≥ 22.6 mg/L). Altered gene expression (22.5 mg/L) and increased cytotoxicity (≥ 180 μg/mL).
[98]
  1. Abbreviations: 5-HT serotonin, AChE acetylcholinesterase, Au gold, BBB blood-brain barrier, BPA Bisphenol-A, CAT catalase, CbE carboxylesterase, Cbz carbamazepine, Cd cadmium, cholinesterase, DA dopamine, EE2 17α-ethinylestradiol, Glu glutamate, GST glutathione-S-transferase, LPO lipid peroxidation, MAO monoamine oxidase, MDA malondialdehyde, MP microplastics, NP nanoplastics, PChE propionylcholinesterase, PE polyethylene, PS polystyrene, ROX Roxithromycin, SOD superoxide dismutase. Asterisks (*) indicate the composition of the plastic particles is not disclosed