Microplastics and human health: unraveling the toxicological pathways and implications for public health

The persistence of plastics in the environment poses significant challenges, as they can remain intact for decades or even centuries. Over time, these materials fragment into smaller particles due to processes such as physical abrasion, chemical reactions, and biodegradation. In 2004, Thompson et al. identified plastic particles approximately 20 μm in size along British coastlines and in marine environments, leading to the introduction of the term “microplastics” (MPs) (5). MPs are now defined as plastic fragments or particles with diameters less than 5 mm, and their widespread presence in daily life results in unavoidable human exposure (6).

MPs can manifest in various forms, with their properties influenced by their origins and the environmental conditions they encounter. Factors such as residence time, the initial structure of primary plastics, and degradation processes—including photodegradation, mechanical wear, and biological contamination—play crucial roles in shaping these particles (7). Generally, fibrous, granular, and fragmented MPs arise from larger plastic items through mechanisms like photodegradation and mechanical action (8). Microplastic particles are typically spherical and range from a few micrometers (μm) to several millimeters (mm) in size, with most diameters falling between 1 mm and a few mm. In contrast, microplastic fibers are longer and narrower than other types of MPs, measuring from 10 μm to several millimeters in length. Due to their small size and varied forms, MPs can easily contaminate food sources, increasing ingestion risk. Furthermore, they tend to accumulate within the human body more readily and are more challenging to eliminate.

Based on the sources of MPs, they can be divided into two major categories: primary MPs and secondary MPs (2). Figure 1 and Table 1 provides an overview of the classification and sources of MPs.

Primary MPs are defined as small plastic particles that are either manufactured at a microscale or produced as by-products during the production process. These particles are specifically designed for various applications, including their use as injection molding powders, abrasive grains, or resin particles (9). Additionally, primary MPs can arise from the wear and tear of larger plastic items throughout their lifecycle, such as the abrasion of tires during driving or the shedding of synthetic fibers during laundering (10). Common forms of primary MPs include microbeads, microfibers, and resin pellets.

Microbeads are tiny plastic spheres, typically measuring less than 5 mm in diameter, that are often found in personal care and cosmetic items such as exfoliating scrubs and toothpaste. Their primary role in these products is to act as abrasives or to enhance texture. Due to their small size, microbeads can easily enter aquatic systems and often evade filtration processes at wastewater treatment facilities (11). Microfibers are fine plastic filaments that originate from textiles like synthetic clothing, carpets, and home furnishings. These fibers can be released at various stages of a textile’s lifecycle, including during production, usage, washing, and even post-treatment. Microfibers are also present in personal care products, including cigarette filters, wet wipes, and face masks (12). Resin pellets serve as raw materials for plastic product manufacturing and can pose environmental risks to aquatic ecosystems if mishandled or accidentally released during production, transportation, or processing (4). These primary MPs have the potential to adsorb and transport hazardous chemicals, thereby increasing their ecological impact.

Secondary MPs are small plastic particles generated from the degradation and fragmentation of larger plastic products such as bags, bottles and Wrapping materials. This breakdown occurs due to mechanical forces like waves and abrasion, chemical reactions, and exposure to ultraviolet radiation from sunlight (13). Given the frequent release of larger plastic items into the environment, secondary MPs constitute the primary components of microplastic pollution. The predominant forms of secondary MPs include fragments and fibers (14). Plastic fragments are unevenly shaped remnants produced through the breakdown of larger plastic items, whereas fibers are slender strands originating from textiles, including garments, ropes, and fishing nets.

The classification of microplastics is closely intertwined with their environmental origins. MPs have numerous sources. Major sources include the use of everyday products (such as detergents, cosmetics), agricultural activities, wastewater discharge, and more (Figure 2).

Inhalation via the respiratory system represents a significant route for the introduction of MPs into the human body (Figure 3), with prior research validating their presence in ambient air (37). Notably, MPs measuring less than 5 μm in length and under 3 μm in diameter are particularly susceptible to inhalation, as they can often evade the mucociliary clearance mechanisms of the upper respiratory tract. Once inhaled, these MPs can disseminate throughout the body via the upper digestive system, ultimately accumulating in various organs (38).

Tire wear, construction materials, and waste incineration are primary contributors to the presence of MPs in outdoor environments (39). Research indicates that approximately 3–7% of particulate matter measuring less than 2.5 μm in the atmosphere originates from tire wear, with an average annual emission rate of 0.81 kg of tire dust per person (40). Additionally, polyethylene and polystyrene are frequently utilized as insulating and molding materials in construction, and the expansion of large-scale architectural projects has led to increased MP emissions (41). A study on emissions from incineration reveals that between 1.9 and 565 microplastic items per kilogram of Municipal Solid Waste (MSW) accumulate in the incinerator’s bottom ash, with the incineration process facilitating their release into the atmosphere (42, 43).

Factors like wind direction, altitude, and population density significantly influence the concentration of MPs in outdoor settings. One study found that urban areas exhibit a higher atmospheric concentration of MPs (13.9 items/m³) compared to rural regions (1.5 items/m³) (44). Another investigation in German cities reported no detectable plastic concentrations in less populated areas (0 particles/m³) (45). Furthermore, this research highlighted elevated MP concentrations near the ground, peaking at a height of 1.7 m—nearly three times greater than those measured at 33 and 80 m (45). Wind direction plays a crucial role in the dispersion of plastic particles; the distribution of MPs is significantly correlated with prevailing wind patterns (45). Consequently, atmospheric MPs tend to accumulate in urban locales, from which they can be transported over considerable distances by wind.

For students and white-collar workers, a significant portion of their time is spent indoors. A recent study found that the concentration of indoor MPs ranges between 1.0 and 60.0 fibers/m³, its main component is polysulfated mucopolysaccharides (a type of MPs). Textiles are a common source of polysulfated mucopolysaccharides in indoor environments, primarily composed of fiber particles such as polyamide, acrylic, and polyester (46, 47). Fiber MPs are the most common type of MPs found in indoor environments. Research has shown that the level of indoor MPs (ranging from 1.0 to 60.0 fibers/m³) is significantly higher than the level of outdoor MPs (ranging from 0.3 to 1.5 fibers/m³) (46). The concentration of polyethylene terephthalate (PET) is between 1,550 and 120,000 mg per kilogram (mg/kg) indoors, which is higher than the range of 212–9,020 mg/kg outdoors (48).

The direction and strength of the airflow generated by air conditioners can affect the migration of polysulfated mucopolysaccharides (a type of MPs) into indoor spaces. A study conducted in student dormitories on airflow testing showed that turbulent airflow can lead to the resuspension of MPs, MPs particles are prone to depositing in open food and drinking water indoors. Moreover, activities such as walking, closing doors, or engaging in some indoor exercises can potentially lead to the resuspension of MPs within indoor spaces (49).

The intake of seafood, such as fish, shrimp, and shellfish, constitutes a major route for MPs to infiltrate the human body. Studies indicate that MPs are commonly found in the tissues and organs of marine species, thereby enabling their transmission to humans via the food chain (50). A survey of the Chinese fishery market revealed that various types of MPs—such as fibers, fragments, and particles—were present in all samples of commercially harvested bivalve shellfish, with particles averaging below 250 μm accounting for 33–84% of the total MPs detected (51). In Indonesia, Rochman et al. discovered that 55% of fish samples were contaminated with MPs, with the majority being less than 500 μm in size and mainly consisting of polyethylene and polypropylene (52).

Bottled drinking water is another significant source of MPs, originating from both the plastic bottles and caps. Over time, degradation of these materials can introduce MPs into the water supply (53). Research indicates that consuming tap water leads to an estimated intake of 4,000 MPs annually, while bottled water consumption can result in an additional intake of approximately 90,000 MPs per year (54). A study by Sherri A. Mason and colleagues analyzed 259 bottled water products across nine countries and found that 93% contained MPs. The average concentration of microplastic particles larger than 100 μm was recorded at 10.4 per liter, with fragments and fibers being the predominant forms. Polypropylene was identified as the most common polymer, comprising 54% of the total (55). In Germany, all bottled water samples tested positive for MPs, with 80% of particles ranging from 5 to 20 mm. Recyclable plastic bottles exhibited the highest average microplastic content at 118 particles per liter, primarily composed of polyester (PET) and polypropylene (PP), while single-use bottles contained an average of 14 particles per liter and beverage cartons had 11 particles per liter, with polyethylene being the common material (56).

Moreover, MPs are found in a variety of food sources such as drinking water, beverages, milk, canned goods, sugar, and salt (57). Studies confirm that low-nutrition organisms are more susceptible to environmental MP contamination. Recent research employing two complementary analytical techniques identified that 32% of MPs smaller than 20 μm were present in drinking water samples. This underscores the need for high-performance filtration systems to enhance purification processes (58, 59). Additionally, a study indicated that the risk of ingesting plastic from mussels is lower compared to exposure to fibers from dust during meals, estimating an annual range of ingestion between 13,731 and 68,415 particles per person (60). Yinan Li and colleagues have also reported that commonly consumed beverages worldwide—including beer, tea, and honey—contain MPs in various forms such as particles, fragments, and fibers. These contaminants are primarily attributed to raw materials as well as environmental exposure during processing and packaging (61).

MPs can enter the human body and other organisms through dermal exposure to a range of topical products, such as cosmetics, body washes, topical medications, and surgical or prosthetic devices. They can also be absorbed through occupational interactions in both indoor and outdoor environments. Under typical circumstances, MPs do not breach the subcutaneous barrier; however, their capacity to penetrate this barrier is primarily determined by their size and chemical characteristics. Particles measuring less than 100 nm are more likely to penetrate the skin due to their smaller size and increased surface reactivity. Furthermore, larger particles may be absorbed via hair follicles, sweat glands, or damaged areas of the skin (62, 63).

Mitochondria serve as the primary source of reactive oxygen species (ROS), and oxidative stress arises from an imbalance between ROS production and the capacity of the antioxidant defense system. MPs can disrupt mitochondrial membrane potential and hinder mitochondrial energy production, contributing to this imbalance (65, 66). Research by Hao Wu et al. demonstrated that polystyrene MPs can induce DNA damage, cell cycle arrest, and necrotic apoptosis in mouse ovarian granulosa cells by enhancing ROS production (67). Furthermore, MPs have been shown to diminish the activity of antioxidant enzymes in vitro, thereby triggering oxidative stress. For instance, polystyrene MPs can lead to hepatocyte apoptosis and alter glycolytic flux through ROS-mediated calcium overload (68, 69).

MPs can stimulate the release of cytokines such as IL-6, IL-8, and IL-10, leading to immune-mediated inflammatory responses that may ultimately result in necrosis of cellular or tissue structures (70). In a murine study, MPs were shown to enhance the expression of inflammatory proteins cPLA2 and COX-1, which subsequently caused renal damage in the mice (71). Research involving chicken cardiomyocytes revealed that MPs could alter the NF-κB-NLRP3-GSDMD and AMPK-PGC-1α signaling pathways due to ROS overload, thereby inducing oxidative stress, pyroptosis in cardiomyocytes, inflammation, and impairments in mitochondrial function and energy metabolism (72). Furthermore, a study conducted on rats suggested that MPs could induce both pyroptosis and apoptosis in ovarian granulosa cells through the NLRP3/Caspase-1 signaling pathway, potentially triggered by ROS (73).

Research has demonstrated that exposure to MPs in zebrafish models leads to a significant upregulation of apoptosis-related genes, including p53, gadd45ba, and casp3b, ultimately resulting in the degradation of gill tissue structure (74). Similarly, another study reported that MPs markedly activated NF-κB, pro-inflammatory cytokines, and apoptosis markers in human microglial cells as well as in mouse brains. This activation included increased levels of BAX, cleavage of PARP, and the activation of caspases 3 and 8, culminating in the apoptosis of microglial cells in both species (75). Additionally, Siwen Li and colleagues found that MPs can induce hepatocyte apoptosis through calcium overload driven by reactive oxygen species (ROS) (68).

In a study measuring various stress indices in zebrafish exposed to MPs, including Lipid oxidative damage, DNA lesions, autophagic process, caspase activation, metabolite alterations, and changes in ventricular contraction frequency and force—parameters that correlate with the fish’s swimming speed—it was determined that DNA damage was the most pronounced effect observed (76). Research involving human peripheral blood lymphocytes revealed that exposure to MPs significantly elevated the frequency of micronuclei (MN), nuclear bridge formation (NPB), and nuclear bud formation (NBUD). Notably, even at lower concentrations, MPs contributed to increased genomic instability. The mechanical interactions between MPs and cells, along with the release of additives from MPs, are potential mechanisms underlying this enhanced genomic instability (77). A further investigation revealed that contact with MPs can lead to DNA lesions in both the mitochondria and nucleus, which results in the movement of double-stranded DNA fragments into the cytoplasm. This event activates the DNA-sensing adaptor protein STING, subsequently initiating the cGAS/STING signaling pathway. This cascade of reactions promotes the translocation of NFκB into the nucleus, where it enhances the expression of pro-inflammatory cytokines, ultimately contributing to liver fibrosis (78). Additionally, a study on fish demonstrated that even at low concentrations, nanoparticles (NPs) can penetrate the nucleus and cause DNA damage, as evidenced by an increased incidence of abnormal erythrocyte nuclei (79). The above cytotoxic mechanisms can further cause multiple organ dysfunction such as nervous system and cardiovascular system.

MPs have the capability to traverse the blood–brain barrier and accumulate within brain tissue. Research indicates that smaller MPs are more likely to penetrate this barrier. For instance, polystyrene microplastic particles (PS-MPs) measuring 50 nm can cross into the mouse brain, where they activate microglial cells and inflict significant neuronal damage (75). Additionally, PS-MPs have been shown to reduce levels of synaptic proteins, disrupt neurotransmitter function, induce neuroinflammation, and lead to deficits in learning and memory in mice (80–82). The neurotoxic effects of MPs are further evidenced by declines in motor abilities across certain species, which manifest as behavioral changes (83). This indicates that MPs could play a role in the onset of neurodegenerative disorders, such as Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease (84–87).

Recent research has identified various types of MPs in different cardiac tissues, with the largest diameter recorded at 469 μm (88). The direct cardiotoxic effects of MPs encompass arrhythmias, compromised cardiac function, pericardial edema, and myocardial fibrosis. At the microvascular level, MPs can induce hemolysis, thrombosis, blood coagulation, and damage to vascular endothelium, primarily through mechanisms involving oxidative stress, inflammation, and apoptosis (89). In an in vitro study utilizing a three-dimensional cardiac organoid model derived from human pluripotent stem cells, exposure to MPs significantly altered the expression of genes associated with cardiac hypertrophy (MYH7B/ANP/BNP/COL1A1), while cardiac-specific markers such as MYL2, MYL4, and CX43 were also notably elevated (90). Additionally, in a zebrafish embryo model, exposure to MPs increased the incidence of thrombosis and exacerbated atherosclerosis by activating and upregulating macrophage receptors. Toxic effects of MPs on the cardiovascular system have also been documented in zebrafish, mouse, and chicken models (Table 1) (91, 92).

The gastrointestinal tract serves as the primary entry point for MPs. Research has demonstrated that the accumulation of MPs in the intestines can activate immune and inflammatory responses in the intestinal mucosa, potentially leading to damage to the mucosal lining (93). Studies indicate that once MPs enter the intestines, they can trigger inflammatory reactions in murine models (94, 95). Additionally, a series of in vitro investigations have revealed that exposure to MPs can result in oxidative stress, DNA damage, inflammatory responses, cell membrane injury, and apoptosis of intestinal epithelial cells, ultimately compromising intestinal barrier function (96–98).

Given that the liver is the main organ responsible for detoxifying exogenous substances, the effects of MPs on liver function are varied. Research involving mice has shown that polystyrene microplastics (PS-MPs) accumulate in the liver and contribute to insulin resistance by promoting inflammation and inhibiting insulin signaling pathways (99). In zebrafish, MPs have been found to induce lipid accumulation and potentially cause histological damage, including necrosis and hemorrhage (100). In mice, liver damage from PS-MPs is indicated by elevated levels of alkaline phosphatase (ALP) aspartate, alanine aminotransferase (ALT), aminotransferase (AST), and lactate dehydrogenase (LDH), alongside hepatotoxicity and dysbiosis of gut microbiota (101). Notably, one study reported that PS-MPs exacerbated lipid metabolism abnormalities in diabetic mice, leading to heightened inflammatory responses. This suggests that individuals with chronic conditions may exhibit increased sensitivity to plastic pollution (102).

Numerous studies have indicated that inhalation of MPs present in the atmosphere can lead to significant pulmonary toxicity and respiratory conditions, including asthma, pneumonia, emphysema, and allergic rhinitis. Animal research has consistently demonstrated that inhaling MPs can trigger pulmonary inflammatory responses, intensify oxidative stress, and even result in pulmonary fibrosis (103, 104). For instance, studies involving the intratracheal administration of amino-polystyrene nanoplastics (APS-NPs) in mice have revealed inflammatory infiltration in lung tissue (105). Moreover, a variety of in vitro investigations have shown that MPs can induce oxidative stress, inflammatory responses, genetic damage, and apoptosis in lung cells (32, 33, 42, 43, 106, 107). Recent findings also suggest that respiratory Ingestion of PS-MPs can disrupt the balance of nasal and pulmonary microbiota (108). Additionally, a clinical cohort study identified a higher concentration of MPs in patients diagnosed with allergic rhinitis (109).

The interplay between MPs and environmental organic compounds can facilitate bioaccumulation and intensify toxic effects in living organisms. For instance, the interaction between F-53B and PS-MPs significantly increased the transcription of pro-inflammatory genes such as cxcl-clc and il-1β, while also elevating the levels of inducible nitric oxide synthase (iNOS) protein in zebrafish larvae, thereby inducing inflammatory stress in these fry (110). Additionally, another study demonstrated that the combination of MPs with polybrominated diphenyl ethers (PBDEs) worsened developmental and thyroid toxicity in zebrafish (81, 82).

MPs can serve as carriers for various environmental heavy metals, such as arsenic (As), cadmium (Cd), and lead (Pb). When these MPs, laden with heavy metals, are introduced into organisms or the human body, they can pose significant health risks. Research involving oysters demonstrated that the presence of MPs combined with arsenic resulted in synergistic effects on gene expression, which in turn led to heightened oxidative stress and increased apoptosis (34, 111).

MPs can also carry potential pathogenic microorganisms, leading to human infections with pathogens such as pathogenic Vibrio species (112). A study has shown that MPs can carry the novel coronavirus, potentially accelerating its spread and infection (113).

In summary, as a carrier of environmental pollutants, microplastics can amplify their health risks by adsorbing organic pollutants, heavy metals and pathogens. This further highlights the need to study the synergistic toxicity of microplastics.