Figure 1
Figure 2
Science-based evidence of adverse health effects of plastic micro and nanoparticles (PMNP)
| Models | Type of plastics | PMNP biological effects | Reference |
|---|---|---|---|
| Ecotoxicity, human cells, human exposure | PE-, PS, PVC-, PET- and PLGAMPs; PS-NPs | Reactive oxygen species (ROS) production (63, 64), activation of antioxidant enzymes (50), increase in glutathione S-transferase (GST) activity (65) and mitogen-activated proteins kinase signalling pathways (66), a decline in lipid digestion and inhibition of digestive enzymatic activities (67), impact on the cell morphology and cell proliferation of immune cells (68, 69) | (36) |
| Ecotoxicity, human cells, human exposure | PE- and PS-MPs | DNA damage via oxidative stress, distortion of cellular proteins involved in cell division, an aberration in signalling responses, down-regulation of transcriptional genes related to apoptotic expressions (70), increased DNA fragmentation in liver tissue, altered activity of antioxidant enzymes and increased lipid peroxidation (71, 72) | (37) |
| Ecotoxicity, human cells | PS-MPs; PS-NPs | Disturbance in lipid metabolism, oxidative stress and neurotoxicity (34), aggregation of serum proteins (73) | (5) |
| Ecotoxicity, human blood cells | PS-NPs | Conformational changes in blood proteins, cytotoxic and genotoxic effects in lymphocytes and erythrocytes | (74) |
| Ecotoxicity | MPs of few microns or less | Adsorption of proteins and local inflammation in the gastrointestinal system (75) | (27) |
| Ecotoxicity, human exposure | Nylon fibres of a respirable size; PE-MPs | Persistent inflammation (7) | (41) |
| Ecotoxicity, animal models, human exposure | PS- and PEMPs; PS-NPs | Decrease in hepatic triglyceride and total cholesterol levels, decrease in gene expression related to lipogenesis and triglyceride synthesis in liver, reduction of intestinal mucus secretion (76), metabolic disorders due to alteration of intestinal microbiota (77), induction of IL-6 and IL-8 expression in gastric adenocarcinoma cells (68), induction of oxidative stress inT98G cells (63), increased AChE activity in the liver (34) | (42) |
| In vivo animal models | PS-MPs | Absence of histologically detectable lesions and no inflammatory responses in mice (23) | (43) |
| In vitro CaCo-2 & THP-1 / T98G & HeLa human cells | PS- and PE-MPs | No cytotoxicity (23, 63) | (39) |
| In vitro model | PS-NPs | Inflammation, oxidative stress, lysosomal dysfunction and apoptosis in cultured cells | (11) |
| In vitro (mouse hepatocytes) | PS-NPs | Oxidative stress and DNA damage (78) | (39) |
| Invertebrates and vertebrates | PS-, PE-, HDPE-MPs | Decreased mucus secretion and mucus secretion-related gene expression (79), down-regulation of genes related to ion transport (76), modified serum levels of IL1α and granulocyte colony-stimulating factor G-CSF, decreased regulatory T cell count and increased the proportion of Th17 cells in splenocytes (80), blood neutrophil counts and IgA levels elevated in dams, and spleen lymphocytes were altered in both dams and offspring (81) | (46) |
| In vitro [red blood cells, peripheral blood mononuclear cells (PBMCs), mast cells] | PS-MPs | No cytotoxic effects on PBMCs and mast cells, haemolysis of erythrocytes, increased IL-6 production | (47) |
| In vitro (intestinal epithelial cell lines, LS174T, HT-29, and Caco-2) | PS-NPs | Reduced cell viability | (22) |
| Rodents | PS-MPs | Accumulation in the liver, kidney, and gut; energy and lipid metabolism disorders, liver inflammation (34), decreased intestinal mucus, changes in intestinal biota (77, 79) | (82) |
| In vitro (epithelial HeLa and cerebral T98G cells) and rodents | PS-MPs | Cells: binding of blood plasma coagulation factors VII and IX leading to a decrease in thrombin generation Mice: accumulation in the liver, kidney and gut with evidence of oxidative stress, energy balance disturbance, and neurotoxicity (83, 84) | (51) |
| In vivo model organisms | PS- and PE-MPs | Blood clots (85), blood cell cytotoxicity (86), oxidative stress (34, 87) | (50) |
| In vitro (CaCo-2 cells) | PET-NPs | No effect on cell viability and membrane integrity, no significant change in apoptosis and necrosis | (48) |
| In vivo, animal models | PS-MPs | Altered hepatic lipid metabolism, decrease in body weight, liver weight, decreased serum triglycerides and total cholesterol, mucus secretion, changes in gut microbiota, impairment of bile acid metabolism (77, 79) | (2) |
| In vivo, animal models | PS-MPs | Mechanical injury, false satiation, low growth rate, increased immune response, energy depletion, blocked enzyme production, decreased fecundity, oxidative stress, morbidity and mortality (88, 89) | (55) |
| In vivo, animal models | PS-MPs; PS-NPs | Inflammatory response, reduced intestinal mucus secretion, damage to the intestinal barrier function leading to an increase in the permeability of the gut mucosa, trigger an imbalance of gut microbiota, and alter metabolism, such as lipogenesis, triglyceride synthesis (77, 79), induction of pro-inflammatory responses (pro-inflammatory cytokines IL6, IL8 and IL1β), and inhibition of cell viability (68) | (54) |
| In vivo | LDPE-MPs | No toxic effects | (90) |
| In vitro (CaCo-2 cells) | PLA particles | No cytotoxicity and no altered cell viability | (9) |
| In vivo, human | Plastic fibres; PS-MPs | Bioaccumulation of synthetic microfibres in the gastro-intestinal tract and lungs of humans (91), inflammation, genotoxicity, oxidative stress, and apoptosis in the human body (92) | (60) |
| In vitro, in vivo | PS-MPs | In vitro: no effects on the phosphorylation of STAT-1 and STAT-6, no effect on the expression of CXCL10 and CCL22, CD209 and CD206 genes. Mice – no statistically significant effects on body and organ weights, no effect on tissue morphology | (23) |
| In vitro (CaCo-2 cells) | PS-MPs; PS-NPs | Increase in intracellular ROS levels, mitochondrial depolarisation, and increased cytotoxicity | (93) |
| Ecotoxicity | PS-NPs | Up-regulation of cytokines involved in gastric pathologies (68), disruption of iron transport (94), induction of apoptosis (22), endoplasmic reticulum stress (95) and oxidative stress (96) | (97) |
| In vitro | Molecularly imprinted polymers; PS-NPs | No significant toxicity | (98, 99) |
Overview of human-relevant exposure pathways for plastic micro- and nanoparticles with numerical data for levels of intake where available
| Biological models | Exposure data | Reference |
|---|---|---|
| Ecotoxicity, human cells, humans | Ingestion route: 11,000 particles from shellfish, 4000 particles from drinking water, and 7–1000 particles from edible sea salt per person per year | (36) |
| Ecotoxicity, human cells, humans | Ingestion route. Sources: seafood, tea bags, honey, sugar, beverage drinks, commercial salts, milk, beer, tap and bottled drinking water | (37) |
| Ecotoxicity, humans | Ingestion sources: drinking water, food containing plastic particles or weathering from plastic containers, salts and honey, and beer | (5) |
| Ecotoxicity, human cells and exposure | Ingestion through the food chain | (27, 31, 38,39,40,41,42,43,44,45) |
| Human exposure | Ingestion route: ≤30 particles/day from tap water and beverages, 37–100 particles/year from sea salt; in total ≤250 pg/kg body weight per day for an adult from tap water, beverages, and sea salt | (11) |
| Rodent model | 5-day oral exposure to 60 nm polystyrene particles: 10 % of the dose found in the gastrointestinal tract | (46) |
| In vitro models | Exposure experiments with red blood cells, peripheral blood mononuclear cells, and mast cells | (47) |
| In vitro models | Exposure experiments with intestinal epithelial cell lines, LS174T, HT-29, and CaCo-2 | (22, 48) |
| In silico models | / | (49) |
| Invertebrates and vertebrates | Exposure through the food chain | (50) |
| In vitro models | Exposure experiments with epithelial HeLa and cerebral T98G cells | (51) |
| In vivo model organisms | Ingestion route: 12,000–204,000 particles per person per year via plastic-contaminated seafood (fish and shellfish), beer, table salt, sugar, and honey | (52) |
| In vitro model of the whole digestive system | Annual ingestion: 123,000 particles for adults (714 mg/day), 81,000 particles for children (449 mg/day). | (53) |
| In vitro models, animal models, plants | Ingestion via the food chain | (54, 55) |
| Human exposure | Annual ingestion: 11,000 particles from shellfish for European top consumer. Ingestion sources: 50.97 particles/L of beer, 24.53 particles/L of soft drinks, 5.79 particles/L of energy drinks, 5.26 particles/L of cold tea, 3 to 11 particles/L of milk; the highest mean concentrations of particles from drink consumption in the US (9.24–11.8 particles/L) and the lowest in Germany (0.91–1.29 particles) | (56) |
| In vivo animal models, mammals | The primary route of exposure: ingestion of food and water contaminated with PMNP; annual consumption of 39,000 and 52,000 particles per person in the US | (57) |
| In vivo | Ingestion of PMNP does not provide a significant contribution to the transfer of absorbed chemicals from the water to the biota via the gut | (10) |
| In vitro, in vivo | The oral bioavailability of 50 nm-sized polystyrene particles differs between 0.2 and 2 % in rodents (in vivo) and humans (in vitro); a relationship between the particle’s composition, size, and uptake has not yet been established | (58) |
| In vivo ecotoxicity (fish) | Estimated exposure from the consumption of Sufflamen fraenatus, Heniochus acuminatus, Pseudotriacanthus, Leiognathus brevirostris, and Atropus atropus for adults: 456, 310, 213, 156 and 121 particles per week, respectively and children: 68, 45, 32, 25 and 19 of particles per week, respectively | (59) |
| In vivo, human | Annual ingestion via shellfish: 11,000 particles for the European population. It is also reported that a regular consumer of sea salt ingests approximately 37 synthetic fibres daily | (60) |
| In vitro, in vivo, human | Estimated exposure for adults: 258 to 312 particles daily | (26) |
| In vitro intestinal barrier | Uptake of ≤0.144 % of polystyrene microparticles across the Caco-2 monolayer | (2, 61) |
| In vitro | Absorption of more than 70 % of nanoparticles with a significant reduction of rate to 30–50 % for microparticles | (62) |
AOPs in AOP-Wiki related to the observed PMNP effects found in the literature search (see Figure 1)[Reported biological effects of PMNP are denoted as molecular initiating events (MIE) or key events (KE) for each AOP_ AOPs marked in the last column with an asterisk are “under development”]
| Reported biological effect of PMNP | Adverse outcome (AO) | Total number of AOPs | Event type in identified AOPs |
|---|---|---|---|
| Increased reactive oxygen species (ROS); oxidative stress induction | Decreased population growth rate/Decreased population size | 8 | MIE in AOP 444*; KE in AOP 386*, AOP 387*, AOP 396*, AOP 299*, AOP 311*, AOP 325*, AOP 326* |
| Lung fibrosis/Lung cancer/Decreased lung function/Dysfunction of the respiratory system | 7 | MIE in AOP 481*; KE in AOP 382*, AOP 319*, AOP 303*, AOP 416*, AOP 451*, AOP 418* | |
| Liver fibrosis/Cholestasis/Steatohepatitis/Liver injury | 5 | KE in AOP 383*, AOP 27*, AOP 213 (open for adoption), AOP 273*, AOP 494* | |
| Breast cancer | 2 | MIE in AOP 294*; KE in AOP 293* | |
| Increased mortality | 7 | MIE in AOP 327*, AOP 328*, AOP 329*, AOP 330*, AOP 186*; KE in AOP 377*, AOP 413 (open for citation & comment) | |
| Reproductive failure/Decreased fertility/Decreased reproductive success/Impaired fertility | 4 | KE in AOP 207*, AOP 476*, AOP 473*, AOP 492* | |
| Treatment-resistant gastric cancer | 1 | MIE in AOP 298 (under review) | |
| Decreased cognitive function | 1 | MIE in AOP 488* | |
| Inflammatory events in light-exposed tissues | 1 | MIE in AOP 282 (under review) | |
| Insulin resistance | 2 | KE in AOP 457*, AOP 497* | |
| Chronic kidney disease | 1 | KE in AOP 384* | |
| Apoptotic cell death | 1 | MIE in AOP 423* | |
| Increased oxidative damage | 1 | KE in AOP 26 (open for adoption) | |
| Increased mesotheliomas | 1 | KE in AOP 409* | |
| Acute myeloid leukaemia | 1 | KE in AOP 432* | |
| DNA damage/DNA strand breaks | Decreased population growth rate/Decreased population size/Decreased population trajectory | 6 | KE in AOP 388*, AOP 444*, AOP 216*, AOP 238*, AOP 396*, AOP 435* |
| Lung cancer | 5 | KE in AOP 303*, AOP 451*, AOP 416*, AOP 417*, AOP 272 (Approved) | |
| Breast cancer | 4 | MIE in AOP 443*, AOP 293*, AOP 294* KE in AOP 200 (open for adoption) | |
| Decreased fertility/Reduced sperm count | 2 | KE in AOP 476*, AOP 322* | |
| Increased mesotheliomas | 1 | KE in AOP 409* | |
| Acute myeloid leukaemia | 1 | KE in AOP 432* | |
| Microcephaly | 1 | KE in AOP 441* | |
| Apoptotic cell death | 1 | KE in AOP 423* | |
| Increased chromosomal aberrations | 1 | KE in AOP 296 (endorsed) | |
| Cataracts | 1 | KE in AOP 478 (open for citation & comment) | |
| Learning and memory impairment | 1 | KE in AOP 483 (open for citations & comments) | |
| Vascular remodelling | 1 | KE in AOP 470 (open for citations & comments) | |
| Increased lipid peroxidation | Increased mortality | 2 | KE in AOP 413 (open for citation & comment), AOP 329* |
| Impaired fertility | 1 | KE in AOP 492* | |
| Apoptosis | Decreased population growth | 3 | KE in AOP 340*, AOP 341*, AOP 444* |
| Decreased fertility/Reproductive failure/Decreased reproduction | 4 | KE in AOP 70*, AOP 71*, AOP 207*, AOP 476* | |
| Orofacial cleating | 2 | KE in AOP 460*, AOP 491* | |
| Breast cancer | 2 | KE in AOP 200 (open for adoption), AOP 439* | |
| Decreased lung function/Chronic obstructive pulmonary disease | 2 | KE in AOP 419*, AOP 452* | |
| Prostate cancer | 1 | KE in AOP 495* | |
| Apoptosis/Necrosis | 1 | AO in AOP 205 (open for comment) | |
| Testicular atrophy | 1 | KE in AOP 212 (endorsed) | |
| Liver injury | 1 | KE in AOP 285* | |
| Thyroid hormone interference | 1 | KE in AOP 393* | |
| Neurodegeneration | 1 | KE in AOP 260* | |
| Kidney failure | 1 | KE in AOP 447* | |
| Lysosomal disruption | Kidney toxicity | 1 | KE in AOP 257* |
| Liver fibrosis | 1 | KE in AOP 144 (under review) | |
| Decreased locomotor activity | Decreased population growth rate | 1 | KE in AOP 218 (not under active development) |
| Decrease in body weight | Decreased body weight | 1 | AO in AOP 6 (endorsed) |
| Glutathione depletion | Impaired fertility | 1 | KE in AOP 492 * |
| Inflammation/Neuroinflammation | Learning and memory impairment | 4 | KE in AOP 12 (endorsed), AOP 17 (endorsed), AOP 48 (endorsed), AOP 490* |
| Parkinsonian motor deficits | 2 | KE in AOP 3 (endorsed), AOP 464* | |
| Lung fibrosis/Bronchiolitis obliterans/Chronic obstructive pulmonary disease | 3 | KE in AOP 206*, AOP 280*, AOP 452* | |
| Cholestasis/Immune-mediated hepatitis/Increased liver steatosis | 2 | KE in AOP 413*, AOP 362* MIE in AOP 62* | |
| Increase, papillomas/carcinomas | 2 | KE in AOP 114*, AOP 115* | |
| Psoriatic skin disease | 1 | KE in AOP 313* | |
| Increased mortality | 1 | KE in AOP 377* | |
| Hyperinflammation | 1 | AO in AOP 392* | |
| Memory Loss | 1 | KE in AOP 429* | |
| Kidney failure | 1 | KE in AOP 447* | |
| Metabolically unhealthy obesity | 1 | KE in AOP 493* | |
| Increased mesotheliomas | 1 | KE in AOP 171* | |
| Breast cancer | 1 | KE in AOP 439* | |
| Pulmonary inflammation | Chronic obstructive pulmonary disease | 1 | KE in AOP 452* |
| Respiratory dysfunction | 1 | KE in AOP 481* | |
| Increased mesotheliomas | 1 | KE in AOP 409* | |
| Increased mortality | 1 | KE in AOP 377* | |
| Hypersensitivity response | 1 | KE in AOP 39* | |
| Atherosclerosis | 1 | KE in AOP 237* | |
| Increased neutrophil activation | Increased thrombo-inflammation | 1 | KE in AOP 412* |
| Mitochondrial dysfunction | Death/Failure, Colony | 6 | KE in AOP 77 (open for comment), AOP 78 (open for comment), AOP 79 (open for comment), AOP 80 (open for comment), AOP 87 (open for comment), AOP 178* |
| Decreased population growth rate | 3 | MIE in AOP 326*, AOP 325*, AOP 324* | |
| Heart failure/Increased mortality | 3 | KE in AOP 479*, AOP 480*, AOP 377* | |
| Kidney failure/Kidney toxicity | 2 | KE in AOP 447*, AOP 437* | |
| Liver fibrosis/Liver injury | 2 | KE in AOP 144 (under review), AOP 273* | |
| Learning and memory impairment | 1 | KE in AOP 48 (endorsed) | |
| Parkinsonian motor deficits | 1 | KE in AOP 3 (endorsed) | |
| Breast cancer | 1 | KE in AOP 200 (open for adoption) | |
| Apoptotic cell death | 1 | KE in AOP 423* | |
| Impaired IL-1R signalling | T-cell-dependent antibody response impairment | 1 | MIE in AOP 277 (under review) |
| Energy reserves depletion/Decreased fatty acid beta-oxidation | Decreased population growth rate | 1 | KE in AOP 97* |
| Decreased body weight | 1 | KE in AOP 6 (endorsed) | |
| Blocked enzyme production (inhibition of aromatase/calcineurin activity) | T-cell-dependent antibody response impairment | 1 | KE in AOP 154 (endorsed) |
| Metastasis, Breast Cancer | 1 | KE in AOP 443* | |
| Decreased fertility | 1 | MIE in AOP 153* | |
| Decreased fecundity/fertility | Decreased fecundity/Decreased population growth rate/Decreased fertility | 13 | AO in AOP 73*, AOP 126*, AOP 345*, AOP 476*, AOP 64*, AOP 66*, AOP 67*, AOP 68*, AOP 70*, AOP 71*, AOP 74*, AOP 153* KE in AOP 444* |
| Oxidation of iron in haemoglobin | Cyanosis | 1 | MIE in AOP 31* |
| Endoplasmic reticulum stress | Non-alcoholic fatty liver disease/Tumorigenesis | 1 | KE in AOP 454* |
| Parkinsonian motor deficits | 1 | KE in AOP 464* | |
| Decreased cholesterol/altered cholesterol metabolism | Impaired fertility | 2 | KE in AOP 51*, AOP 18 (under review) |
| Decreased sperm quantity and/or quality in the adult testis | 1 | MIE/KE in AOP 69* | |
| Decreased cognitive function | 1 | KE in AOP 487* | |
| Altered lipid metabolism | Steatohepatitis | 1 | KE in AOP 401* |
| Pancreatic acinar tumours | 1 | KE in AOP 166* | |
| Metabolic syndrome/stress | Metabolic syndrome/Insulin resistance | 1 | AO in AOP 497* |
| Death/Failure, Colony | 1 | KE in AOP 81 (open for comment) | |
| Increased blood CCK level (satiety) | Pancreatic acinar cell tumours | 1 | KE in AOP 316* |
| Cell injury | Learning and memory impairment | 5 | KE in AOP 48 (endorsed), AOP 13 (endorsed), AOP 12 (endorsed), AOP 17 (endorsed), AOP 490* |
| Liver fibrosis/Liver injury/ | 5 | KE in AOP 38 (endorsed), AOP 144 (under review), AOP 278*, AOP 273*, AOP 494* | |
| Decreased growth | 3 | KE in AOP 265*, AOP 264*, AOP 266* | |
| Heart failure/Increased mortality | 2 | KE in AOP 479*, AOP 377* | |
| Neurodegeneration | 1 | KE in AOP 281* | |
| Inhibition of digestive enzymatic activities (trypsin inhibition) | Pancreatic acinar cell tumours | 1 | MIE in AOP 316* |
| Alteration in intestinal microbiota | Gut dysbiosis | 1 | KE in AOP 428* |
| Decrease in gene expression related to liver | Increased hepatocellular adenomas and carcinomas | 1 | KE in AOP 107 (under review) |
| Covalent protein binding | Sensitisation of skin | 1 | MIE in AOP 40 (endorsed) |
| Increased allergic respiratory hypersensitivity response | 1 | MIE in AOP 39* | |
| Meiotic spindle disorganisation | Increased aneuploid offspring | 1 | KE in AOP 106 (EAGMST under review) |
| Increased mortality | Increased mortality | 23 | AO in AOP 16*, AOP 96*, AOP 104*, AOP 113*, AOP 160*, AOP 161*, AOP 138*, AOP 177*, AOP 186*, AOP 312*, AOP 155 (endorsed), AOP 156 (endorsed), AOP 157 (endorsed), AOP 158 (endorsed), AOP 159 (endorsed), AOP 363 (under review), AOP 377*, AOP 364 *, AOP 365 *, AOP 399 (open for citation & comment), AOP 413 (open for citation & comment), AOP 410 (open for citation & comment), AOP 450* |
| Decreased population growth rate | Decreased population growth rate | 54 | AO in AOP 23 (endorsed), AOP 25 (endorsed), AOP 29*, AOP 30 (under review), AOP 100*, AOP 122(under development), AOP 123*, AOP 155 (endorsed), AOP 156 (endorsed), AOP 157 (endorsed), AOP 158 (endorsed), AOP 159 (endorsed), AOP 101*, AOP 102*, AOP 63*, AOP 103*, AOP 310*, AOP 16*, AOP 312*, AOP 334*, AOP 336*, AOP 337*, AOP 338*, AOP 339*, AOP 340*, AOP 341*, AOP 297*, AOP 346*, AOP 326*, AOP 325*, AOP 324*, AOP 363 (under review), AOP 348*, AOP 376 (open for citation & comment), AOP 386*, AOP 387*, AOP 388*, AOP 389*, AOP 364*, AOP 365*, AOP 399 (open for citation & comment), AOP 410 (open for citation & comment), AOP 216 *, AOP 238*, AOP 299*, AOP 311*, AOP 444*, AOP 138*, AOP 177*, AOP 97*, AOP 203*, AOP 218 (not under active development), AOP 219 (not under active development), AOP 323 (open for citation & comment) |