Table 1 Assessment of plastic particles in rodent models
From: Consequences of nano and microplastic exposure in rodent models: the known and unknown
Ref | Model | Polymer | Size | Route | Controls | Dose | Duration | Accumulation/effects |
|---|---|---|---|---|---|---|---|---|
Oral administration | ||||||||
 Liang et al. [23] | C57BL/6 mice | PS (pristine or fluorescent) | 50, 500, and 5000 nm, alone or in mixture | Oral gavage | Double distilled water | 2.5, 25, 50, 125, 250, 500 mg/kg bw | Single dose, 24 h. Daily, 28 days | Single-dose: bioaccumulation over time in intestines (IVIS). Bioavailability in other organs was size-dependent, with small particles in the gut, liver, spleen, kidneys, heart, lungs, testis, epididymis, brain, blood, ovaries, and uterus. Larger particles were found in the blood and gut but not in other organs. They have altered mucus production in the gut. Co-exposure with different sizes increased biodistribution in organs and increased ROS generation, epithelium apoptosis, and permeability in the intestines. Antioxidant pre-treatment was able to reverse the effects. The 28-day repeated exposure model showed the same effects |
  Amereh et al. [30] | Wistar rats | PS | 25 and 50 nm as mixture | Oral gavage | Distilled water | 1, 3, 6, 10 mg/kg bw-day | Daily, 35 days | Decreased serum testosterone, luteinizing hormone, follicle-stimulating hormone, altered sperm concentration, motility, morphology, DNA damage. Histopathological signs of testes atrophy and degeneration and particles accumulation |
 Deng et al. [35] | CD-1 mice | PE (coated with phthalate esters) | 0.4 to 3.2 µm | Oral gavage | Pure water, phthalate esters, virgin MP | 100 mg/kg bw | Daily, 30 days | Phthalate ester accumulation in gut > liver > testes. Testes: reduced sperm count and viability, increased oxidative stress (SOD, MDA), increased spermatogenesis disorder markers LDH and ACP by MP contaminated with phthalate ester |
 Stock et al. [38] | C57BL/6 HOTT reporter mice | PS (fluorescent carboxyl or sulphate coated) | 1, 4, and 10 µm in mixture | Oral gavage | 0.5% (m/v) carboxymethylcellulose | 1.25 – 34 mg/kg bw adjusted for surface area | Three times a week, 28 days | No effects observed: no Hmox1 reporter response or changes in body or organ weights and low intestinal particle retention. No pathological changes were measured by histology, and very low concentrations of particles in the intestines |
 Deng et al. [41] | ICR mice | PS (pristine or fluorescent) | 5 and 20 µm | Oral gavage | Water | 0.01–0.5 mg/day | Up to 28 days | Accumulation in gut, liver, and kidney. Liver inflammation, hepatic lipid accumulation, oxidative stress, decreased AChE activity, altered lipid profile, and impairment of energy metabolism (reduction in ATP levels) |
 Li et al. [48] | C57BL/6 mice | PE | 10–150 µm | Diet | Basal feed with no special preparation | 6, 60, and 600 µg/day, adjusted for 3 g consumption/animal | 35 days | Increased IL-1α in serum and different serum cytokine profiles depending on concentration. Small intestinal inflammation: increased TLR4, AP-1, and IRF5 protein (IF) and increased microbial diversity and abundance from fecal samples at the highest concentration of MP |
 Ding et al. [46] | SPF grade C57BL/6 mice | PS (fluorescent) | 60 nm | Oral gavage | Double distilled water | 50 µg/mL (500 µL) | Single-dose, 3 days | Particle accumulation in the stomach, intestines, and liver. No accumulation was observed in the heart, spleen, and lungs |
 Jin et al. [49] | ICR mice | PS (pristine or fluorescent) | 5 µm | Drinking water | Reverse osmosis pure water | 100 and 1000 µg/L | 42 days | Accumulation in the gut was followed by gut microbiota dysbiosis and decreased mucous secretion. Intestinal barrier dysfunction. Significant increase in hepatic total bile acid (ns increases in serum) and altered bile acid metabolites. Altered amino acid metabolism: increased serum arginine, tyrosine, and succinylacetone |
 Luo et al. [50] | ICR mice | PS | 5 µm | Drinking water | Water | 100 and 1000 µg/L | During pregnancy and lactation (about 6 weeks) | Altered serum and hepatic metabolic markers; different levels of genes related to glycolipids and energy metabolism in dams, F1 and F2 offspring. No influences on F1 and F2 growth rate. Dams: hepatic ballooning degeneration. Altered gut microbiota and decreased mucus secretion. F1: altered serum metabolites. Adult female F1: lipid accumulation in the liver |
 Luo et al. [51] | ICR mice | PS | 0.5 and 5 µm | Drinking water | Water | 100 and 1000 µg/L | During pregnancy (about 6 weeks) | Increased risk of fatty acid metabolism disruption in offspring: In both sexes, 5 µm particle exposure reduced β-oxidation and fatty acid synthesis. Amino acid metabolism is reduced in females |
 Walczak et al. [52] | Fischer 344 rats | PS (fluorescent non-coated, aminated and carboxyl-modified) | 50 nm | Oral gavage | Deionized water | 125 mg/kg bw | Single dose, 6 h | All particles were observed in the lung, heart, kidneys, brain, stomach, and intestines. Negative NP was also in the liver. Estimated bioavailability: from 0.2 to 1.7%. No histopathological changes |
 Li et al. [69] | C57BL/6 mice | PS (fluorescent) | 5 µm | Drinking water | Reverse osmosis water | 20 mg/kg/day bw | 30 days | Particle accumulation in the liver. Vacuolar degeneration, chronic inflammatory infiltration, and hepatocellular edema (histologically). Increased IL-1β and TNF-α mRNA (hepatic). Signs of apoptosis (TEM). Increased Nrf2 and Keap1 hepatic protein. Liver oxidative stress: decreased SOD and GSH, increased MDA |
 Deng et al. [70] | CD-1 mice | Suspended PE and PS in organic flame retardants (OFR) | 0.5 to 1.0 µm | Drinking water | Water | 2 mg/L (PE or PS) in 10 or 100 µg/L (OFR in aqueous solution) | 90 days | Accumulation in liver and gut, with local inflammation and lipid droplets (H&E). Hepatic oxidative stress and LDH increased in MP + OFR, decreased AChE in the brain, and altered metabolomics in serum and liver |
 Jin et al. [71] | BALB/C mice | PS (fluorescent) | 0.5, 4, and 10 µm | Oral gavage | Double distilled water | 10 mg/mL | Daily, 28 days | Testicular accumulation followed by local inflammation. Reduced sperm quality and testosterone levels. Disruption of blood-testis barrier and disordered arrangement of spermatogenic cells with the presence of multinucleated gonocytes (H&E) |
 Lu et al. [79] | ICR mice | PS | 0.5 and 50 µm | Drinking water | Reverse osmosis water | 100 and 1000 µg/L | 35 days | Decreased body, liver, and epididymis fat weights. Decreased mucus secretion in the gut. Altered biochemical serum markers. Changes in microbiota, hepatic lipid profile, and expression of some genes related to lipid metabolism decreased triglyceride synthesis markers mRNA in fat tissue |
 Silva et al. [84] | Swiss mice | PUR | 250 nm | Oral gavage and IP | 0.9% NaCl | 2, 5, and 10 mg/kg bw | 10 days | Oral gavage: increased visceral fat accumulation, glomerular atrophy, and increased serum TNF-α and ALP. IP: glomerular necrosis and inflammatory infiltrate in adipose tissue on the high dose. Both administration routes: lung inflammation, liver vascular congestion, and hepatocytes vacuolization. Increased ALT levels and serum IL-6 |
 Zheng et al. [85] | C57BL/6 mice | PS | 5 μm | Drinking water | Distilled water | 500 µg/L | 28 days | Exacerbated acute colitis model: increased intestinal permeability, lipid and liver metabolites disruption, triglyceride accumulation, and lipid peroxidation in the liver. Increased serum IL-1β, TNF-α, and INF-γ in mice exposed only to MP. In addition, MP exacerbated serum cytokines in the colitis model |
 Xie et al. [87] | BALB/c | PS | 5.0–5.9 μm | Oral gavage | 0.9% NaCl | 0.01, 0.1 and 1 mg/d or 1 mg/d + NAC or p38 MAPK inhibitor | Daily, 42 days | Decreased sperm number, motility, metabolism markers LDH and SDH, serum testosterone, and GSH. Increased sperm deformity rate, ROS, MDA, apoptosis, and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Rescued by N-acetylcysteine and SB203580 |
 Hou et al. [88] | ICR mice | PS | 5 µm | Drinking water | Water | 100, 1000 and 10,000 µg/L | 35 days | Sperm count decreased, and deformities increased. Disordered arrangement of spermatic cells. Increased NF-κB, IL-1β, IL-6, and testicular apoptosis. Decreased HO-1 protein and Nrf2 protein and mRNA |
 Hou et al. [90] | Wistar rats | PS | 0.5 µm | Drinking water | Deionized water | 0.015, 0.15 and 1.5 mg/kg/d | 90 days | Increased thickness of granulosa layer with some thinner secondary follicles (H&E) and decreased number of growing follicles. Decreased antioxidant defenses (GPx, SOD, and CAT). Increased MDA in ovaries, and NLRP3 and caspase-1 in ovarian granulosa cells (high dose). IL-1β and IL-18 increased, and anti-Müllerian hormone decreased |
 An et al. [91] | Wistar rats | PS | 0.5 µm | Drinking water | Water | 0.015, 0.15 and 1.5 mg/d | 90 days | Decreased number and volume of growing follicles and ovary fibrosis in high concentration. Decreased anti-Müllerian hormone and decreased ovarian reserve capacity. Increased MDA and decreased antioxidant enzymes (SOD, CAT, GPx). Increased apoptosis, Wnt, and TGF-β in ovaries |
 Park et al. [93] | ICR mice | PE (containing surface modification with acid and hydroxyl groups) | 40 to 48 µm | Oral gavage | Water | 3.75, 15 and 60 mg/kg body weight | Daily, 90 days, some females exposed more than 21 days (lactation period) | 90 days exposed males: decreased body weight gain, changes in hematological parameters. 90 days exposed females: altered hematological parameters and spleen immune response parameters, and increased serum IgA. 90 days exposed mice: hypertrophy/hyperplasia of stomachs mucosa. No adverse symptoms were observed in dams during gestation or lactation. Pups: altered sex ratio and growth rate, altered spleen immune response parameters |
 Rafiee et al. [98] | Wistar rats | PS | 25 and 50 nm | Drinking water | Distilled water, dispersing reagent (surrounding medium) | 1, 3, 6, 10 mg/kg body weight | Daily, 5 weeks | No effects observed: no differences in body weight. Neurobehavioral assessment alone. No cognitive changes |
 Li et al. [100] | Wistar rats | PS | 0.5 µm | Drinking water | Deionized water | 0.5, 5 and 50 mg/L | Daily, 90 days | Myocardium vascular congestion and accumulation of MP. Thinner and ruptured tissue in high dose followed by increased serum cardiac damage markers CK-MB and Troponin I. Increased MDA and reduced antioxidant enzymes in the heart. Increased myocardium apoptosis and fibrosis mediated by Wnt/β-catenin pathway activation |
Amereh  et al. [101] | Wistar rats | PS | 25 and 50 nm mixture | Oral gavage | Distilled water | 1, 3, 6 and 10 mg/kg body weight/day | Daily, 5 weeks | There were no effects on T3 and T4 hormones in serum; however, circulating active forms of thyroid hormones (FT3 and FT4) were decreased in rats. Increased TSH levels in high-dose. Changes in cholesterol serum markers and increased levels of liver damage markers (ALT and AST) |
Inhalation/airways | ||||||||
 Eyles et al. [27] | BALB/c mice | Scandium-46 labelled styrene-divinyl benzene | 7 µm | Intranasal instillation | Absent control group | 0.250 mg (47.5 kBq) in 50 or 10 μl PBS | 24 days | 50 µL dose: substantial bronchopulmonary deposition, accumulation on liver and spleen. 10 µL dose: accumulation in nasopharyngeal regions only |
 Lim et al. [58] | SD rats | PS | 0.1 µm | Inhalation | Fresh air control | 0.68 × 105, 1.38 × 105 and 2.82 × 105 particles/cm3 | 6 h each day, 5 days/week for 14 days (Modified OECD TG 412) | Serum AST and lung inspiratory time decreased in males. Respiratory frequency increased and inspiratory/expiratory time decreased in females. In females, reduced leukocytes count. Inflammatory markers: TGF-β and TNF-α increased in lung dose-dependently in both sexes. No changes in body weight or food consumption. No concentration–response was observed |
 Fournier et al. [59] | SD rats | PS (fluorescent) | 20 nm | Intratra-cheal instilla-tion | 0.9% NaCl | 2.64 × 1014 particles | 24 h | Accumulation in maternal lungs, heart, and spleen. Fetal liver, lungs, heat kidney, and brain. Significantly lower fetal and placental weights when adjusted for litter size variation. No differences in maternal weight or number of fetuses per litter |
Other routes | ||||||||
 Estrela et al. [22] | Swiss mice | PS (fluorescent) and/or ZnO | PS NP: 23 nm ZnO: 69 nm | IP | Water | 14.6 ng/kg | 3 days | In separate, both particles induced cognitive impairment, redox imbalance (increased nitric oxide levels and thiobarbituric acid reactive species), and suppressed acetylcholinesterase activity. Systemic DNA damage was observed in separate and combined injections of particles |
 Kaga et al. [24] | Athymic nude mice | Radiolabelled PEGylated PS | Spherical: 21 and 33 nm, rod-like: 37 nm diamet., 350–500 nm length, worm-like: 45 nm diamet., 1–2 μm length | IV | Absent control group | 0.1 mg in 50 µL PBS (2 mg/mL) | 48 h | All particles accumulated in the liver, spleen, kidneys, heart, lungs, pancreas, thigh muscle, and tumor with different biodistribution |
 Hu et al. [94] | C57BL/6-mated BALB/c mice | PS | 10 µm | IP | 0.9% NaCl | 250 µg in 200 µL saline | Pregnant mice on embryonic days 5.5 and 7.5 | Increased embryo resorption rate and decreased number and diameter of uterine arterioles in the placenta of MP. Decreased leukocytes in blood, spleen, and placenta of dams. Decreased NK cells and macrophages in the placenta. Changes in macrophages polarization favoring M2-subtype, increased T CD4 + cells in the placenta, and changed cytokines secretion |
 Nie et al. [95] | ICR mice | PS | 60 and 900 nm | IV | 0.9% NaCl | 300 µg | Pregnant mice on embryonic days 8, 9,10 and 15 | No effects on number of embryos. Decreased body weight of embryos. 60 nm NP: decreased placental diameter, extravasation in fetus and placenta |