Unveiling the toxicity of micro-nanoplastics: A systematic exploration of understanding environmental and health implications

Abstract

The surge in plastic production has spurred a global crisis as plastic pollution intensifies, with microplastics and nanoplastics emerging as notable environmental threats. Due to their miniature size, these particles are ubiquitous across ecosystems and pose severe hazards as they are ingested and bioaccumulate within organisms. Although global plastic production has reached an alarming 400.3 MTs, recycling efforts remain limited, with only 18.5 MTs being recycled. Currently, out of the total plastic waste, 49.6 % is converted into energy, 27 % is recycled, and 23.5 % is recovered as material, indicating a need for better waste management practices to combat the escalating pollution levels. Research studies on micro-nanoplastics have primarily concentrated on their environmental presence and laboratory-based toxicity studies. This review critically examines the sources and detection methods for micro-nanoplastics, emphasising their toxicological effects and ecological impacts. Organisms like zebrafish and rats serve as key models for studying these particle's bioaccumulative potential, showcasing adverse effects that extend to DNA damage, oxidative stress, and cellular apoptosis. Studies reveal that micro-nanoplastics can permeate biological barriers, including the blood-brain barrier, neurological imbalance, cardiac, respiratory, and dermatological disorders. These health risks, particularly relevant for humans, underscore the urgency for broader, real-world studies beyond controlled laboratory conditions. Additionally, the review discusses innovative energy-harvesting technologies as sustainable alternatives for plastic waste utilisation, particularly valuable for energy-deficient regions. These strategies aim to simultaneously address energy demands and mitigate plastic waste. This approach aligns with global sustainability goals, providing a promising avenue for both pollution reduction and energy generation. The review calls for further research to enhance detection techniques, assess long-term environmental impacts, and explore sustainable solutions that integrate energy recovery with pollution mitigation, especially in regions most affected by both energy shortages and increased plastic waste.

Graphical Abstract

Highlights

• •Comprehensive study of micro-nanoplastics' origins, pathways for understanding distribution, impact.
• •Systematic assessment of micro-nanoplastics' impact on organisms' health, potential risks.
• •Micro-nanoplastics as carriers of pollutants, altering environmental systems.
• •Identifying knowledge gaps to guide future research, bridging understanding gaps.

1. Introduction

Plastics are artificial materials primarily composed of organic polymers and supplemented with various chemical additives like bisphenols, phthalates, and flame retardants, which confer distinctive properties on plastic items [1], [2]. Due to their affordability, ease of manufacturing, versatility, and hydrophobic nature, plastics find widespread usage across numerous commercial sectors [3]. However, despite the escalating production rates of plastics globally, effective strategies for reusing, recycling, and repurposing have not been universally adopted, particularly in certain developing nations [4], [5], [6]. The significant surge in plastics production poses significant environmental and ecological threats. In 2022, global plastic production reached a staggering 400 MTs, with polypropylene (PP) being the most produced polymer, and out of total plastics production only 18.5 MTs of plastic waste were recycled, with nearly half of the (49.6 %) of plastic waste was utilised for generating energy, 27 % of plastics litter were recycled, and 23.5 % recovered as material [7], [8]. The increasing global production of plastic, with China (32 %) being the top producer, followed by North America (17 %) and Europe (14 %) (Fig. 1(a)).

Fig. 1.

(a) A Geographic View of Plastic Pollution: Mapping Production and Waste by Region, (b) Distribution of global plastics production by polymer type, (c) Origins of Micro and Nanoplastics Pollution.

Plastics are categorised based on their durability and composition as either thermosets or thermoplastics [7]. Thermosets like polyurethane, epoxy, and alkyd are favoured for applications requiring insulation, adhesion, and plywood, owing to their heat-induced crosslinking, forming irreversible covalent bonds [9]. In contrast, thermoplastics such as polyethylene (PE), PP, polystyrene (PS), and polyvinyl chloride (PVC) lack such bonds, making them recyclable and mouldable [4], [10]. PP is the most produced polymer globally, followed by low-density polyethylene (LDPE), PVC, and high-density polyethylene (HDPE) (Fig. 1(b)). These polymers are found in a plethora of products including plastic bags, bottles, containers, and furniture. PP is commonly used in bottle caps, straws, containers, and automotive components [11], while PS is prevalent in foam packaging, food containers, cups, and discs [12], [13]. PVC is extensively employed in plumbing, curtains, windows, and flooring [14]. In the textiles industry microplastic fibres are mainly composed of polyester (PES) or PP, including clothing, agricultural, industrial, and household textiles [15]. These fibres are prevalent in various environments and products, with scientific research focusing primarily on PE, PS, and PVC due to their widespread use and environmental impact [16].

Upon entering the environment, plastic waste undergoes interactions with various environmental components, leading to the degradation of larger plastic pieces into smaller plastic debris (Fig. 1(c)) [4], [10], [17]. These smaller plastic fragments, known as microplastics (MPs), are measured under 5 mm. Moreover, further degradation can give rise to even smaller particles called nanoplastics (NPs) ranging from 1 to 1000 nm [14]. Due to their minute size, NPs are challenging to remove and tends to accumulate in different environmental systems, contributing to plastic pollution that adversely affects plant and animal life. Notably, the size of these particles plays a crucial role, as smaller NPs offer a larger surface area, potentially causing more harmful effects [18], [19]. In the current scenario, microscopic plastic particles are intentionally manufactured and incorporated into various consumer products, such as personal care items. Upon disposal, these products contribute significantly to direct sources of plastic pollution in the environment [11], [20], [21], [22]. Over the years micro-nanoplastics and other xenobiotics have emerged as critical environmental concerns, with a significant number of studies documenting their prevalence across various components—including oceans, rivers, air, drinking water, sediments, and food sources indicates that exposure to these plastic particles can have adverse effects on organisms in marine, terrestrial, and human systems [23], [24].

Comprehensive reviews have assessed the impact of micro-nanoplastics on numerous organisms, including zooplankton [25], microalgae [26], aquatic species [27], and terrestrial animals [28]. Zebrafish have emerged as a key model for studying the accumulation and toxicity of micro-nanoplastics [29], [30], [31]. In biomedical research, zebrafish are particularly valued for their applications in studying human diseases [32], drug discovery [33], and environmental toxicology [34]. Key advantages include their small size, low maintenance requirements, rapid reproduction, and transparent embryos and larvae, which facilitate live imaging and tracking of fluorescently labelled micro-nanoplastics [35]. Zebrafish’s external embryonic development allows for non-invasive observation, yielding reliable outcomes in toxicity studies. Genetic manipulability and the availability of transgenic lines, such as those expressing enhanced green fluorescent protein (EGFP), further enhance zebrafish’s utility for high-throughput screening. Studies on zebrafish have shown that micro-nanoplastics exposure can induce significant inflammation, oxidative stress, and disrupt metabolism, growth, and reproduction [36], [37], [38], [39]. Standard protocols from the Organisation for Economic Co-operation and Development (OECD) and the Environmental Protection Agency (EPA), such as the zebrafish embryonic toxicity test (ZFET TG 236), provide reliable methods to assess hatching rates, survival, deformities, and overall toxicity. In these protocols, chemicals may be introduced to zebrafish embryos through diffusion or direct injection, ensuring robust and reproducible results [40].

Further, research involving animal models, particularly rodents, has revealed the harmful effects of micro-nanoplastics on physiological functions and development. Studies show that MPs, sized 5–150 μm, can induce inflammation in the intestines of mice, disrupt the gut microbiome, affect liver lipid metabolism, and contribute to gastrointestinal and liver toxicity [41]. While MPs generally remain within the digestive tract, 293 nm NPs can cross the blood-brain barrier and may interact with α-synuclein fibrils, which could promote the progression of Parkinson’s disease by encouraging the spread of α-synuclein pathology across susceptible brain regions [42]. In reproductive studies, mice exposed to micro-nanoplastics of varying sizes (20 nm, 0.5 μm, 4 μm, and 10 μm) showed testicular accumulation of these particles, histological changes, and reduced hormone levels essential for germ cell development [43], [44]. Additionally, pregnant mice exposed to 10 μm MPs exhibited higher rates of embryo resorption and smaller placental diameters, potentially impeding embryonic development [45]. There is also evidence that maternal exposure to nanoplastics during late gestation results in the transfer of these particles into various foetal organs [46]. Additionally, maternal mice ingesting micro-nanoplastics through water experienced significant foetal growth restrictions during late pregnancy [47].

Subsequently, micro-nanoplastics are increasingly found in food and air, raising concerns about potential human exposure through various routes, including ingestion, inhalation, and skin contact. Despite their widespread presence, the specific effects of these particles on human health are not fully understood [48]. The extensive global production of plastics and inadequate waste management practices have contributed to the ubiquity of micro-nanoplastics in our environments [49]. Their longevity in the ecosystem is alarming, as they break down at a very slow rate. These particles can directly enter the human body, or they may serve as carriers for harmful environmental pollutants [50]. Research indicates that micro-nanoplastics are commonly found in food samples , and their accumulation in the food chain could adversely affect organs, particularly the gastrointestinal tract [51]. Furthermore, airborne micro-nanoplastics can infiltrate the respiratory system, posing significant risks to lung health. Extended exposure, particularly in occupational settings, has been linked to an increased risk of respiratory diseases [52]. Additionally, evidence suggests that MPs can interact and migrate through various tissues in the body [53]. Acting as vectors for antibiotics and heavy metals, MPs facilitate the distribution of these contaminants in the environment, ultimately leading to human exposure through inhalation, ingestion, or dermal contact, thereby presenting indirect health hazards [54].

These particles also pose significant environmental risks by accumulating and transporting harmful pollutants and heavy metals, which can bioaccumulate in marine and terrestrial life, escalating toxicity concerns [55]. Thus, to assess the global prevalence of micro-nanoplastics contamination, the development of advanced and effective detection methods is essential. While recent research advancements have enabled the detection of micro-nanoplastics, standard methods for identifying micro-nanoplastics in marine or terrestrial environments are still limited. But due to their small size, NPs are generally assumed to be present alongside MPs, but their detections and remediations pose challenges. However, under laboratory conditions, various techniques have proven useful, including UV–VIS spectrometry, Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Size Exclusion Chromatography (SEC), Atomic Force Microscopy (AFM), Mass Spectrometry (MS), Fourier Transform Infrared Spectroscopy (FT-IR), Raman Spectroscopy (RS), Differential Scanning Calorimetry (DSC), Fluorescence Spectroscopy (FS) and Thermal Extraction Desorption Gas Chromatography-Mass Spectrometry (TED-GC-MS). Additionally, methods like Field Flow Fractionation (FFF) and Dynamic Light Scattering (DLS) are also employed to analyse these contaminants (particle size) [9], [56], [57].

Till date, removing micro-nanoplastics from the environment remains challenging due to their tiny size. Filtration methods, like reverse osmosis and distillation, can filter particles down to 0.001 µm but are costly and require intensive upkeep, limiting broad application [58]. Density separation using high-density solutes (e.g., sodium or zinc chloride) shows promise but lacks industrial scalability [59]. Other approaches, such as adsorption, coagulation, and photocatalytic degradation, are effective but often limited by high costs and operational demands [60], [61], [62]. Filtration methods using granular media or membranes stand out for efficiency and low environmental impact, with materials like sand, biochar, and nanofibers proving effective in capturing MPs. Enhancements like biochar or metal oxide frameworks also help improve filtration by reducing membrane fouling [63], [64]. Eco-friendly adsorbents, including clay, metal hydroxides, nanomaterials, photocatalysts like TiO₂ and ZnO, Fe₃O₄, and carbon materials offer additional solutions by breaking down MPs into safer by-products, though developing scalable solutions remains essential [65], [66], [67], [68], [69], [70], [71]. The integration of these optimised nanomaterials offers a sustainable and energy-efficient approach to micro-nanoplastics degradation. Moreover, the scalability of these technologies is promising for industrial applications, aligning with goals for sustainable water treatment and environmental preservation.

In future, environmental conditions could become rapidly hazardous if current issues, such as plastics pollution, are not properly addressed. Over millions tons of plastic waste enter the ecosystem every year, and plastic production is expected to triple if current trends persist [72]. While the environmental impact of micro-nanoplastics pollution is severe, these pollutants hold great potential for renewable energy generation. Utilising plastic waste for energy, especially when integrated into power systems, offers a sustainable solution for managing pollution and supporting energy needs. This approach aligns with circular economy goals and has the potential to promote both economic growth and environmental sustainability [73]. Energy recycling from micro-nanoplastics waste can convert non-recyclable materials into renewable sources such as heat, electricity, biofuels, biohydrogen, bioethanol, hydrocarbons, gas, and char through various biological, chemical, physical, and thermal processes [74], [75], [76], [77]. Numerous works over the years have raised concerns about micro-nanoplastics pollution in the environment [22], [78], [79], [80], [81], [82], [83]. While substantial research has focused on assessing the toxicity of various pollutants, integrating insights from diverse environmental compartments, including zebrafish, rats, and human health, there remains a lack of studies exploring the potential use of these materials for utilisation including energy generation. This study thoroughly examines the potentially harmful effects of micro-nanoplastics on various organisms, including zebrafish, rats, and humans. The novelty of this review lies in its systematic examination of micro-nanoplastics, highlighting their accumulation, distribution, and harmful effects on biological systems in various organisms. By utilising a multi-species approach, this review provides a unique and integrated perspective on the effects of these pollutants across different trophic levels and pathway for energy recovery. It also explores energy harvesting strategies from micro-nanoplastics waste to develop alternative fuel sources.

2. Source and detection of micro-nanoplastics

The widespread presence of micro-nanoplastics across various environmental domains underscores the urgent need to understand their sources and devise effective detection methods. These minute plastic particles pervade diverse ecosystems, from oceans and freshwater bodies to terrestrial habitats and even human bodies [78], [83], [84], [85], [86].

2.1. Sources of micro-nanoplastics

Micro-nanoplastics emission vary significantly across regions, influenced by factors such as population density, economic activity, and waste management practices [87]. The breakdown of larger plastic items through road paint degradation, tire abrasion, and textile waste leaching contributes heavily to microplastic generation, eventually producing micro-nanoplastics [11]. Approximately 75–90 % of plastic pollution in aquatic environments originates from land-based sources, while the remaining fraction comes from marine sources [88]. Key contributors include littering, inadequate waste disposal, and landfill leakage, alongside single-use plastics and natural events like floods that introduce plastics into ecosystems [89]. Synthetic textiles, particularly PES, are also significant sources; washing a single item can release over 1900 fibres into wastewater, and daily wear disperses additional fibres into the air [90], [91]. Marine-based sources of plastic pollution include fishing activities, cargo loss, ocean dumping, and aquaculture debris [4], [92]. PS and PP are particularly concerning due to their prevalence and ease of fragmentation. Activities such as thermal cutting of PS foam and 3D printing with PP also release nanoparticles [13]. Even biodegradable nanoparticles, such as those used in drug delivery, add to environmental plastic burdens [93], [94], [95]. Although larger plastic particles in cosmetics may not pose an immediate risk, they can gradually degrade into nanoparticles over time.

Industrial discharges, especially from sectors like cosmetics and wastewater treatment facilities, contribute significantly to environmental micro-nanoplastics contamination [13], [96]. Approximately 0.8–2.5 MTs of micro-nanoplastics enter oceans each year, though wastewater treatment plants capture about 95 % of these particles within biosolids. When these biosolids are used as fertilisers, substantial quantities of micro-nanoplastics are introduced to agricultural land, potentially impacting plant growth. Furthermore, agricultural practices, including aquaculture and improper waste disposal, introduce micro-nanoplastics directly into soil and marine environments [97]. In Europe, about 63,000 to 430,000 tons of micro-nanoplastics contaminate agricultural lands annually, while North America contributes around 44,000 to 300,000 tons, and Australia adds 2800 to 19,000 tons [98], [99]. Micro-nanoplastics enter soils through various means, such as plastic films, greenhouse equipment, biosolids, treated wastewater, and littering [100]. Compost derived from organic waste also adds to soil contamination, with plastic particles commonly found up to 25 mm in size, with smaller fractions below 2 mm. Some regions, like Australia, have enacted regulations limiting plastic content in composts to help mitigate this issue [101], [102]. Moreover, the use of NPs in manufactured products, including paints, adhesives, coatings, medical devices, and electronics, leads to their unintentional release during product use and disposal [93], [103], [104]. In the last few years, many companies have actively phased out micro-nanoplastics in their products, and several U.S. States and European countries have banned these particles in personal care products. While these measures may reduce emissions, they cannot eliminate micro-nanoplastic pollution, as primary sources are relatively minor contributors [100], [101].

2.2. Detection of micro-nanoplastics

There are several approaches for determining the chemical composition of MPs including the density gradient technique with detecting elemental composition like pyrolysis-gas chromatography coupled with various detection techniques [14], [105], [106]. Most of the methods have shown that it can be used to identify different types of MPs for different kinds of samples. However, those techniques have limitations in detecting the size of MPs. On the other hand, RS has exhibited the capacity to identify MPs at sub-micron levels and has arisen as a critical innovation in this field [106]. Accurately detecting and chemically identifying NPs in the environment pose significant challenges [107]. Studies have reported difficulties in quantifying their concentration and identifying specific types, such as weathering-derived NPs versus primary sources. However, recent research advancements offer promising solutions.

A SEM generates high-resolution images by directing an electron beam across a sample’s surface, causing electrons to interact with the sample’s atoms. These interactions produce signals that reveal details about the surface’s structure and topography. SEM provides valuable information on the physical form and structure of MPs; however, to examine the material composition of MPs, it is often paired with Energy-dispersive X-ray Spectroscopy (EDS). EDS enhances SEM analysis by adding elemental data, which allows qualitative and quantitative assessment of the particles [112]. Wang et al., employed optical microscopy and SEM-EDS were applied to study MPs in fish from the Atlantic and Pacific Oceans [113]. While both techniques could describe the shape, size, and morphology of MPs, only SEM-EDS could accurately distinguish plastic from non-plastic particles. Additionally, a researcher analysed water samples from lakes in Russia, observing degraded surfaces on MPs due to environmental exposure, with EDS confirming particles as PVC based on chlorine detection [114]. Similarly, Bhatia et al. expressed the use of SEM-EDS on sediment samples from Dhaka riversides, identifying PE, PP, and polyethylene terephthalate (PET) as the most common microplastic [115].

RS, based on the inelastic scattering of light, is used to analyse molecular structures by examining molecular vibrations and rotations, as the scattered light frequency differs from the incident light [116]. This technique offers high sensitivity, precision, specificity, and spatial resolution below 01μm, making it effective for identifying polymers without the need for sample preparation, staining, or damaging samples [117]. However, fluorescence from organic and inorganic compounds, particularly in coloured additives, can interfere with Raman scattering, making detection challenging due to the generally weak Raman signal [118], [119]. Nonlinear RS is gaining traction in MP detection for its high signal-to-noise ratio and minimal fluorescence interference [120]. Additionally, surface-enhanced Raman spectroscopy (SERS) is increasingly applied due to its high sensitivity and chemical specificity. These advancements in Raman techniques hold promise for rapid in situ MP detection in water, potentially addressing identification challenges in liquid environments [121]. Whereas, FTIR spectroscopy, complementing RS, identifies chemical bonds by comparing spectral peaks with reference libraries [122]. FTIR enhances the detection of MPs down to 10 μm, offering environmental benefits like high-throughput screening with minimal sample requirements [123], [124]. However, FTIR’s spatial resolution can be affected by moisture, requiring samples to be dried for accuracy. Additionally, weak signals for very small MPs may lead to occasional false positives or negatives, with detection varying based on particle thickness and characteristics [125], [126], [127].

For instance, Shim et al. investigated the fragmentation of expanded PS beads into micro- and nano-sized particles using SEM and energy-dispersive X-ray spectroscopy (EDS) [128]. Similarly, Rangasamy et al., utilised SEM and FTIR to characterise PE-MPs [129], while Velzeboer et al., and Yang et al., employed light microscopy and TEM for the characterization of PS and PET-NPs [130], [131]. In another study, Satish et al. [132] assessed MPs found in high and low-tide sediment samples from five coastal regions of Tamil Nadu, India, using SEM-EDAX. Microplastic concentrations ranged from 439 ± 172–119 ± 72 items/kg (HTL) and 179 ± 68–33 ± 30 items/kg (LTL). The primary polymers identified included PE (73.2 %), followed by PP (13.8 %), nylon (8.2 %), PS (2.8 %), and PES (2 %). Further, Lee et al., utilised FE-SEM, FTIR, and RS to analyse micro-nanoplastics in eyeglass polishing wastewater, demonstrating the effectiveness of these techniques [106]. Human activities significantly contribute to plastic debris generation, with LDPE-MPs commonly found in coastal waters [133]. Wastewater treatment plants are major sources of LDPE-MPs, with facial cleansers and laundry products contributing significantly to their presence. Estimates suggest that billions of MPs are discharged daily in different parts of the world [134], [135].

While Raman spectroscopy effectively detects MPs [128], other chromatographic techniques like pyrolysis-gas chromatography-mass spectrometry (PY-GC-MS) and Thermal Extraction Desorption Gas Chromatography-Mass Spectrometry TED-GC-MS identify even smaller NPs [79], [136]. Pyrolysis combined with gas chromatography and mass spectrometry (Py-GC/MS) is a thermoanalytical technique used to determine the types and concentrations of polymers present in a sample [79]. Unlike spectroscopic methods, which require smaller samples, PY-GC-MS necessitates larger quantities. However, this method does not provide information about the size and shape of MPs because they undergo thermal degradation during the analysis [137]. Ribeiro et al. [138] employed PY-GC-MS to detect MPs in seafood, successfully identifying and quantifying PS, PE, PVC, PP, and polymethyl methacrylate (PMMA). Similarly, Gomiero et al. [139] applied this technique to analyse drinking water samples, revealing that PE, polyamide (PA), and PES were the most commonly detected polymers. Despite their accuracy, these methods face limitations such as complex procedures and high costs. Hyperspectral imaging (HSI) emerges as a promising alternative for rapid and efficient microplastic detection, offering the ability to differentiate polymers from organic matter and estimate particle size and shape [140], [141]. This rapid progress in detection methods highlights the growing problem of MPs, urging solutions to curb their sources and mitigate the environmental impact (refer to Table 1).

Table 1.

Methods for Detecting Micro-nanoplastics: Utilisation, Benefits, Drawbacks, and Environmental Friendliness.

S.No.	Analytical methodology	Lower limit of detection	Advantages	Reference
1	DLS	1 nm	Measures hydrodynamic size and zeta potential of particles; estimate particle size distribution; non-destructive	[108], [109]
2	AFM	100 nm	High-resolution imaging, is used to understand the morphology, nanostructure, and adhesive behaviour of small-sized particles	[110]
3	TEM	1 nm	High-resolution imaging, enabling the visualisation of micro-nanoplastics at the nanoscale level. Its ability to provide detailed structural information makes it invaluable for the accurate detection and characterization of micro-nanoplastics in environmental samples	[111]
4	Fluorescence spectroscopy	Micro-size range	Screening nanoparticles, is non-destructive	[105]
5	SEM	Nm range	High-quality imaging allows particle surface characterisation, when coupled to EDS provides an elemental composition	[108]
6	FTIR	> 300 μm	Little to no sample preparation; non-destructive analysis	[109]
7	RS	> 300 μm	Better response to non-polar plastic functional groups than FTIR, has higher spatial resolution and is insensitive to sample thickness than FTIR	[108], [109]
8	PY-GC MS	1 μg polymer dependent/ 34.5 μg NP/g	No need to pre-process samples, simultaneous identification and quantification of polymer and related organic additives	[108], [109]

3. Zebrafish exposure to micro-nanoplastics

Zebrafish, known as Danio rerio, represents a prevalent model organism in toxicological research focused on assessing aquatic toxicity. It is a popular aquarium fish, frequently sold under the trade name zebra, danio, widely used in biomedical studies, cancer research, cardiovascular disease, human motor neuron disease, and cerebrovascular disease, with 70 % of human protein-coding genes [142], [143], [144], [145]. This genetic resemblance underscores its aptitude for exploring toxicity induced by micro-nanoplastics. Furthermore, zebrafish plays a crucial role in global environmental monitoring endeavours led by pollution control boards, contributing to the evaluation of water contamination in diverse natural settings such as rivers, lakes, and ponds [146], [147]. They assist in gauging the repercussions of industrial discharges on water quality. Additionally, they emerge as pivotal assets in assessing toxicity linked to persistent organic pollutants in freshwater sources [18]. Their myriad advantages, encompassing high fecundity, observable embryos, rapid development, fully sequenced genome, availability of characterised mutants, and cost-effectiveness, render them highly appealing to researchers. Moreover, their diurnal sleep cycle, mirroring aspects of mammalian sleep behaviour, amplifies their utility across diverse research domains [78], [148]. Zebrafish larvae were exposed to MPs, copper (Cu), and combined Cu+MPs at different concentrations (0.04 ng/L, 34 ng/L, and 34 μg/L), have shown to cause developmental, vascular, cytotoxic, and oxidative stress-related changes. The exposed group exhibited reduced survival rates compared to control groups. Behavioural observations revealed that increased copper concentrations and its combinations with MPs notably decreased average swimming speed, total distance travelled, and turning angle, suggesting the xenobiotics altered swimming abilities. Additionally, exposed larvae displayed impaired avoidance behaviour, failing to respond to adverse stimuli. Biochemical assays indicated a significant decrease in AChE activity in all exposed groups when compared with controls, with the most substantial inhibition observed in larvae exposed to MPs and Cu+MPs [149].

3.1. Distribution of micro-nanoplastics

In recent times, micro-nanoplastics have been frequently detected in oceans, rivers, lakes, and sewage systems [83], [150]. Due to their minute size and limited biodegradability, zebrafish can consume micro-nanoplastics, leading to accumulation. The ingestion of micro-nanoplastics can result in various adverse effects such as mortality, diminished feeding, hindered growth, oxidative stress, immune system dysfunction, and genotoxicity [151], [152] (refer to Table 2). Several studies have demonstrated that micro-nanoplastics are consumed by a variety of marine organisms including zebrafish. and tends to accumulate in specific tissues such as the brain, gills, gastrointestinal tract (GIT), gut, circulatory system, etc. [153], [154] (refer to Fig. 2. (a)). This understanding of biodistribution underscores the critical need to elucidate the factors governing particle penetration across different organs. Experimentation elucidating the biodistribution of particles following waterborne exposure suggests a common occurrence of particle accumulation in the gastrointestinal tract [155]. Notably, particles can enter organisms not only through direct uptake from the surrounding environment but also via ingestion of contaminated food sources.

Table 2.

Distribution, bioaccumulation, effects of micro-nanoplastics in Zebrafish.

S. No	Model animal	Particle type/ size	Duration	Bioaccumulation/effects	References
1	Zebrafish (embryos/ larvae)	PS-NPs 50 nm	120 pf	NPs presence in the pericardium, pancreas, liver and GI tract. Different polymer accumulated in the pattern PP > PVC > PE	[157]
2	Adult Zebrafish	Water	Six and twenty-four hours	MPs can transfer persistent organic pollutants not only via ingestion, but also by simple attachment to epithelia or via the water column	[29]
3	Adult Zebrafish	PE-MPs 10–600 μm	Ninety-six hours	MPs were detected in the gills, intestine. Reduced feeding, up-regulation of vtg1 and cyp1a gene.	[31]
4	Zebrafish (embryos and larvae)	PS-NPs (44.7 nm)	24 hpf	NPs can absorb additional contaminants causes’ heart malformation and deformities in the jaw, fin, and tail.	[35]
5	Zebrafish embryos	PS/50 nm	24–48 hpf	Nanoplastics induced significant changes in hatching rate, developmental malformation, cell death, and survival. These alterations were further enhanced with co-contaminants (Au ion)	[152]
6	Zebrafish embryos	PVC MPs	--	MPs delay hatching rate in zebrafish embryos, and down-regulates cardiac development genes.	[1]
7	Adult Zebrafish	PS-NPs (50 and 100 nm)	--	MPs cause aggregation of neutrophils and apoptosis in the abdomen of larvae. Significant inflammation in the hepatic cells.	[158]
8	Parental and offspring Zebrafish	-	45 days	Combined exposure causes decrease in the number of eggs and the locomotor behaviour, Alters hatching rate, mortality, body length	[159]
9	Adult Zebrafish	PS-NPs	45 days	Reduced CAT, AchE activity and GSH levels	[38]

Fig. 2.

(a) Uptake and accumulation of micro-nanoplastics in adult zebrafish, larvae, and embryos. (b) PS-NPs distribution in the chorionic membrane or in vivo of F1 embryos/larvae (8–120 hpf) post exposure to various particle sizes of PS-NPs (Reproduced with permission from Zhou et al. [165], Elsevier).

Recently, it is reported that degradation of PS-MPs may have profound effects on the oxidative stress parameters and cause DNA damage, and developmental toxicity in zebrafish [156]. Subsequently, an investigation was carried out and reported the uptake and subsequent accumulation of PS-MPs in the liver and gut of zebrafish after a 7-day exposure period [154]. They observed the presence of 5 µm and 20 µm PS-MPs, suggesting that smaller MPs may infiltrate the circulatory system and reach the liver. Furthermore, they noted early inflammatory responses, including vacuolation, and necrosis, in hepatic cells. Furthermore, MPs cause oxidative stress and significantly increase the activity of superoxide dismutase (SOD) and catalase (CAT) enzymes. Pitt et al., demonstrated the ability of PS-NPs to traverse the zebrafish chorion, a significant barrier to external substances [157]. The PS-NPs were characterised by DLS. These particles predominantly accumulated in the yolk sac, head, pericardium, gallbladder, pancreas, liver, and (GIT). Similarly, Mak et al. investigated the toxic impact of PS-MPs (20–600 µm) in adult zebrafish for a period of 96 hrs at varying concentrations (11 particles/L), moderate (110 particles/L), and high (1100 particles/L). They found that smaller particles were more easily ingested and accumulated within the fish. In these groups, 61 ± 10 % of the fish showed MPs remaining in their intestines, occupying up to 89 ± 6 % of the intestinal space, which restricted available area for food. Behavioural responses and changes in gene expression were assessed. Moreover, medium-concentration exposure resulted in elevated expression of the cyp1a gene in the intestine, while both medium and high concentrations led to significant up-regulation of the vtg1 gene in the liver. Behavioural abnormalities, such as seizures and a downward-bent tail, were also observed at these exposure levels, indicating potential neurotoxic and physiological disturbances linked to MPs ingestion [31].

Similarly, in 2019, a researcher explored the behavioural changes induced by PS-NPs in zebrafish larvae, finding significant accumulation in various organs [160]. Sökmen et al. documented significant bioaccumulation of PS-NPs in zebrafish embryos, specifically in the brain, with physical deformities. TEM and zetasizer analysis confirmed the nanoscale size of the PS-NPs, measuring approximately 20 ± 3.2 nm and averaging 18.43 ± 0.28 nm, respectively. Findings indicated that these nanoparticles not only accumulated in brain tissue but also induced oxidative DNA damage. Through TEM, PS-NPs were visualised in the brain providing clear evidence of their presence. This bioaccumulation was linked to increased mortality rates, widespread physical abnormalities, heightened reactive oxygen species (ROS) production, and apoptosis, particularly concentrated in brain tissue [161].

Chen et al. found a significant accumulation of PS-MPs in the gills and GIT of adult zebrafish. Moreover, metabolomic studies indicated increased oestrogen levels, potentially contributing to hyperactivity [82]. Similarly, Teng et al. discovered that the presence of PS-NPs in the zebrafish brain and gastrointestinal tract resulted in diminished growth, heartbeat, stunted growth and development [38]. Further, De-Marco et al. exposed zebrafish larvae with 10 μm PS-MPs at 200 particles/mL for a period of 120 hpf (hours post-fertilization). MPs were found to cause significant changes in survival rate, development of larvae, hatching time, and tail deformities in larvae [162]. Besides this, MPs were also found to up-regulate the expression of genes involved in oxidative stress SOD and CAT and cellular detoxification glutathione S transferase and cytochrome (GST and CYP). In the same way, Rangasamy et al. [129] exposed adult zebrafish to environment-relevant concentrations of PE-MPs (5 and 50 μg/L). In this study, SEM provided visual confirmation of particle size and shape, while FTIR analysis verified the presence of PE-MPs in the GIT of zebrafish. They also examined oxidative stress and antioxidant responses in the liver and brain. Findings indicated that CAT and GST activity in the liver was significantly reduced. However, after 20 days, GST activity in the liver increased in a concentration-dependent manner among fish exposed to PE-MPs. Lipid peroxidation (LPO) levels were notably elevated, particularly in the brain, after 20 days of exposure. Additionally, the rise in Na+ -K+ -ATPase activity in the gills correlated with increased malondialdehyde (MDA) production, implying a compensatory mechanism. This elevated enzyme activity likely helps regulate ion loss linked to heightened LPO processes.

Furthermore, researchers have also investigated the effects of PS-NPs on oxidative stress and anti-apoptotic genes at 120 hpf zebrafish embryos were investigated [163]. Results showed dose-dependent down-regulation of the heat shock protein gene (hsp70) and activation of genes related to oxidative stress (SOD 1&2), apoptosis (cas1&8), and inflammation at higher NPs concentrations. Notably, genes associated with DNA repair were down-regulated, while mitochondrial metabolism-related gene expression remained unchanged. The study suggests that PS-NPs induced cellular stress leading to alterations in gene expression without causing mortality. Similarly, the study conducted by Mansuri et al. aimed to evaluate the impact of leached plasticizers, namely dibutyl phthalate (DBP), diethyl phthalate (DEP), and di-ethylhexyl phthalate (DEHP), from MPs on the development of zebrafish larvae. The researchers observed that exposure to these phthalates led to increased mortality rates and significant morphological alterations in the larvae compared to the control group. Additionally, the study revealed changes in gene expression patterns related to cardiovascular development, dorsoventral axis formation, tail malformation, and floorplate development in the larvae exposed to plasticizers. These findings highlight the potentially detrimental effects of leached plasticizers from MPs on the development of aquatic vertebrates, emphasising the need for further investigations into this area [164]. In a recent study, Zhou et al. employed zebrafish as a model organism to investigate the neurotoxic effects of PS-NPs of varying particle sizes on zebrafish embryos at environmentally relevant concentrations. Their findings revealed that PS-NPs across all particle sizes induced developmental toxicity, manifested by neuronal loss, axonal degeneration, shortening, and hybridization, as well as genetic alterations associated with apoptosis and developmental processes [165]. Consequently, these effects culminated in aberrant behaviour in the zebrafish embryos. Notably, the smaller size of PS-NPs facilitated their entry into the embryo and brain before hatching, potentially exacerbating their neurotoxic effects. Furthermore, PS-NPs with diameters of 100 and 1000 nm demonstrated the ability to disrupt neuronal signalling and impair the GABAergic, cholinergic, and serotonergic systems (Fig. 2b). Further, they observed bioaccumulation and distribution of PS-NPs in embryos when exposed to 10 mg/L solutions. Larger PS-NPs (1000 nm) primarily adhered to the membrane surface, while smaller ones (100 nm and 500 nm) penetrated the membrane, reaching the embryo interior.

Similarly, Bashirova et al. conducted an investigation on the bioaccumulation and toxicity mechanisms of NPs derived from polyethylene terephthalate (PET). Through the innovative use of high-resolution magic-angle spinning (HRMAS) NMR-based metabolomics, toxicity assays, and behavioural endpoints, the research provided a holistic understanding of how PET-NPs affect zebrafish embryos. The study revealed significant impacts on hatching time and survival rates, along with the accumulation of PET NPs in crucial organs like the liver, intestine, and kidney where reactive oxygen species were localised. The HRMAS NMR data demonstrated alterations in metabolites related to liver function, detoxification pathways, oxidative stress, mitochondrial membrane integrity, and cellular bioenergetics [166]. Recently, a study by Chen et al. investigated the uptake, distribution, and toxic effects of PS-NPs with different sizes (80, 200, and 500 nm) in embryonic and juvenile zebrafish. Results displayed that all three sizes of NPs could cross the chorion, adsorb by the yolk, and distribute into various organs such as the intestinal tract, eye, brain, and dorsal trunk, albeit with different patterns. The organ distribution and observed toxicities varied depending on the size of the NPs, with larger particles inducing significant oxidative stress and smaller particles influencing the expression of neural and optical-specific mRNAs [167].

3.2. Behavioural changes

Behavioural changes have demonstrated more sensitivity and serve as significant endpoints in toxicological investigations. The neurophysiological integrity in zebrafish is crucial for maintaining normal behaviour, and it is highly sensitive to pollutants. Plastic particles, known for their ability to induce sublethal effects in marine life, present an opportunity to utilise zebrafish locomotor activity as a sensitive measure for assessing environmental contamination [168], [169]. Chen et al. examined the effects of PS-NPs on zebrafish larvae, revealing a surprising link between particle size and behaviour. Exposure to 50 nm PS-NPs led to reduced movement, hinting neurotoxicity. Co-exposure with micro and nanoplastics mitigated the negative effects of 17α-ethynylestradiol on locomotion, indicating a competitive binding mechanism [170]. Additionally, increased expression of genes associated with vision and neural structure was observed in the exposed group. Mak et al. demonstrated that exposure to MPs induced abnormal behaviour in adult zebrafish, likely due to cellular disruption and increased ROS production [31]. Similarly, Limonta et al. observed decreased swimming activity in zebrafish larvae exposed to NPs, indicating potential circadian rhythm disruption or impaired motor function. These studies highlight the intricate relationship between micro-nanoplastics exposure and behavioural changes in zebrafish, emphasising the need for further research into their potential neurological impacts. Furthermore, the study found a reduction in body length and a decline in the activity of Acetylcholinesterase (AChE), a crucial enzyme for proper nerve transmission. Reduced AChE activity is a well-established indicator of neurotoxicity, suggesting that NPs might be negatively impacting the nervous system of developing zebrafish. These findings in both adult and larval zebrafish highlight the potential neurotoxicological effects of micro-nanoplastics, raising concerns about the broader ecological implications of plastic pollution in aquatic environments [171]. In a study conducted by Sarasamma et al., adult zebrafish were subjected to exposure to PS-NPs, with their movements meticulously monitored in a specialised tank test. This experimental approach capitalises on the innate behaviour of zebrafish in novel environments: initially diving in response to the unfamiliar setting, followed by a gradual escalation in vertical movement as anxiety diminishes and exploratory behaviour ensues. Strikingly, zebrafish exposed to PS-NPs exhibited distinct alterations in their movement patterns, suggesting a potential disruption in their exploratory behaviour and anxiety response [172]. This observation corroborates findings by Sökmen et al., who demonstrated that PS-NPs, when administered via the yolk sac, can accumulate in the brain, potentially influencing neurological function and contributing to the observed behavioural changes. These investigations underscore the capacity of NPs to perturb the delicate equilibrium between anxiety and exploration in zebrafish, thus prompting concerns regarding their broader neurobehavioral ramifications on aquatic organisms [161]. Furthermore, researchers documented a noteworthy increase in locomotion hyperactivity in zebrafish following a 7-day exposure to MPs [82]. Also, esearchers investigated the combined effects of MPs and copper (Cu), (heavy metal pollutant) in zebrafish larvae [149]. They observed exposure to MPs alone or with Cu significantly reduced survival rates and swimming activity. Additionally, zebrafish exposed to these contaminants displayed a weakened avoidance response, suggesting impaired nervous system function. This decline in escape behaviour could leave them vulnerable to predators. Furthermore, the study linked these behavioural changes to a decrease in an enzyme crucial for healthy nerve signalling.

Another study by a group of researchers explored the impact of Avobenzone, a common sunscreen ingredient, and NPs on zebrafish larvae [173]. They discovered that both Avobenzone and NPs accumulated in the larvae, with NPs even enhancing Avobenzone uptake. Exposure to either contaminant alone altered gene expression related to the nervous system and vision, potentially affecting behaviour. Moreover, combined exposure led to a further decline in swimming activity, suggesting a synergistic effect on neurological function. These findings raise concerns about the potential for sunscreens and other emerging pollutants to interact with MPs in aquatic environments, creating a complex web of threats to fish health and behaviour. Similarly, Chen et al. investigated the effects of various MPs on zebrafish development and behaviour [174]. While minimal impacts were observed at environmentally relevant concentrations, exposure to higher microplastic doses led to an increase in embryonic death rate and a faster heartbeat in developing zebrafish. Chronic exposure during the larval stage, however, did not affect feeding or growth but did inhibit swimming activity and reduce AChE enzyme activity. AChE plays a critical role in nervous system function, suggesting potential neurotoxicity from MPs exposure. Similarly, Aliakbarzadeh et al. explored the chronic effects of PS-NPs on zebrafish neurological function. Their findings indicate that both individual and combined exposure with an endocrine disruptor (nonylphenol) caused oxidative stress, disrupted key neurotransmitter systems, and impaired energy metabolism [175]. Notably, these effects were often more severe in combined exposures, raising concerns about potential synergistic toxicity of pollutants. Additionally, the study observed histological evidence of neural cell damage, highlighting the potential for long-term neurological harm. These studies, along with others, portray a concerning picture of how micro-nanoplastics can disrupt crucial behavioural patterns in zebrafish [161], [165]. Recent studies have explored how exposure to MPs can alter the behaviour of zebrafish. In 2022, a researcher investigated the effects of PS-NPs on zebrafish embryos, finding it caused hyperactivity and disrupted swimming patterns compared to virgin PS [176]. This disruption stemmed from A-PS impacting the development of motor neurons and neurotransmitter function. Also, Zhang et al., examined the effects of PS-MPs on zebrafish embryos. Their findings showed PS-MP exposure increased deformities, but interestingly, when combined with a pollutant (3,6-dibromocarbazole), it reduced overall stress levels in the embryos. This suggests MPs may act as carriers for other contaminants, influencing their overall toxicity. These studies, along with observations of erratic swimming and seizure-like behaviours, highlight the potential consequences of MP exposure on a fish's ability to navigate, escape predators, and find food [177].

4. Rats exposure to micro-nanoplastics

Micro-nanoplastics undergo complex transportation routes in terrestrial environments influenced by various external factors such as water flow, animal activity, and human actions. Although data exists on the presence and toxicity of micro-nanoplastics, their impacts on animals are still insufficiently comprehended, and the quantification of exposure levels remains inadequate [178]. Research addressing these gaps is crucial for effective risk assessment. To investigate the impact of micro-nanoplastics on human health, researchers have utilised mice or rats as model animals (Fig. 3(a)). Rats or mice holds a unique place in scientific research, being the first mammal species domesticated for such purposes. Compared to others, rats/mice offer distinct advantages in studying complex functions like cognition, memory, and even the mechanisms behind breast cancer, diabetes, and human reproduction [179]. Their larger size allows for repeated blood draws, enabling scientists to track the uptake of micro-nanoplastics through dietary intake and their subsequent elimination through faeces. Faeces provide a non-invasive way to directly assess micro-nanoplastic ingestion [180]. However, accurately quantifying these tiny plastic fragments presents a significant technical hurdle. The extraction process must be meticulously designed to remove organic matter from the samples without damaging the micro-nanoplastics themselves. Ideally, the chosen digestion method should be not only cost-effective and time-saving but also ensure effective removal of organic material while preserving the integrity of the various polymers present in micro-nanoplastics. Only through overcoming these technical challenges can we unlock the secrets surrounding the potential health impacts of micro-nanoplastics on rats, paving the way for a more comprehensive understanding of their influence on the broader animal kingdom.

Fig. 3.

(a) Illustrates micro-nanoplastics uptake and accumulation in rats. (b) Shows effects of PS-NPs and Cd exposure, highlighting: (A) Heart pathologies, (B) body weight changes, (C) heart weight, (D) heart coefficients (%), (E) Ultrastructural findings: broken myofilaments, swollen mitochondria, (F) H&E staining, (G) Masson's trichrome staining, (H-I) Western blot analysis for CTnT protein levels, and (I) Proportion of fibrosis area (%). (Reproduced with permission from Ye et al. [85]).

4.1. Distribution of micro-nanoplastics

The distribution of micro-nanoplastics within rats is a dynamic and complex topic of ongoing research, crucial for understanding their potential health and ecological impacts. Early studies demonstrated oral absorption of PS beads in rats, with smaller particles accumulating more readily in the liver and kidney [177], [178]. In the last decade, researchers emphasise the size-dependent nature of micro-nanoplastics distribution, with smaller particles exhibiting greater translocation and accumulation in various organs compared to larger ones [178], [181], [182], [183]. A critical study was carried out which investigated the specific pathways through which MPs enter a rat's body after oral ingestion. Traditionally, uptake was thought to occur mainly through Peyer's patches, specialised immune tissue with M cells facilitating uptake. However, their research challenges this idea, showing uptake in both regular BALB/c mice and SCID mice lacking MALT. After oral gavage, both groups exhibited uptake within 5 minutes, increasing significantly after 30 minutes. Interestingly, in BALB/c mice, almost 96 % of particles were found outside Peyer's patches, suggesting an independent uptake mechanism. SCID mice, lacking MALT, also displayed similar particle uptake via the villous route [184].

Simon and Sabliov, carried out a comprehensive review and delved into the biodistribution patterns of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPRs) for drug delivery purposes [185]. Utilising databases like Science Direct and Web of Science, the review focused on studies investigating the biodistribution of PLGA NPRs administered intravenously (i.v.) or orally in mice and rats. The analysis was limited to papers providing biodistribution data in various organs such as the liver, kidney, spleen, lung, heart, and brain, expressed as % dose particles/g tissue. Observations highlighted organ-specific particle behaviour, influenced by factors like particle size, animal model, indicator type (entrapped or covalently linked), and delivery method (oral or i.v.). In mice, the liver exhibited the highest particle uptake, whereas rats showed the highest uptake in the lung. Minimal particle presence was noted in the heart and brain of both species, with concentrations decreasing significantly over 24 hours post-administration in rats. Smaller particles tended to accumulate more in the liver, kidney, and spleen. Orally delivered NPs demonstrated limited uptake within the initial 24-hour period compared to i.v. delivery. Discrepancies in particle concentrations between rats and mice were observed, as expected, considering differences in organ size and metabolism. Additionally, particles with covalently linked indicators exhibited lower tissue concentrations than those with physically entrapped indicators. In a study by Walczak et al., the oral bioavailability of nanoparticles was assessed in rats, showing that negatively charged NPs were significantly taken up in organs such as the kidney, heart, stomach wall, and small intestinal wall [179]. Results revealed a range of 0.2–1.7 % bioavailability in vivo, lower than in vitro estimates (1.6 % - 12.3 %). In 2016, Silva et al. conducted in vivo studies on Swiss albino mice to evaluate the biocompatibility of polyurethane nanoparticles (PU-NPRs) when administered both orally and intraperitoneally. The findings showed that oral administration of PU-NPRs at three different concentrations led to a notable increase in visceral fat accumulation. Additionally, mice given the highest dose of PU-NPRs intraperitoneally exhibited diffuse mononuclear inflammatory infiltration in their fat tissue. Histopathological analysis revealed signs of inflammation and cell damage across multiple organs: inflammatory infiltration and vacuolization of hepatocytes in the liver, inflammation and vascular congestion in the lungs, and glomerular necrosis in the kidneys. This study highlights potential adverse impacts of PU-NPRs on various tissues, raising questions about the safety and biocompatibility of these materials in biomedical applications [186].

Lu et al., investigated the impact of PS-MPs on male mice (0.5 and 50 µm) at a concentration of 1000 µg/L five weeks [187]. The results revealed several adverse health effects in the exposed groups, including reduced body, liver, lipid weights, diminished gut mucus secretion, and shifts in gut microbiota diversity. Analysis of the gut microbiome, using sequencing of the V3-V4 region of the 16S rRNA gene, revealed marked alterations in microbial richness and diversity. Operational taxonomic unit (OTU) analysis further identified shifts in 310 and 160 gut microbes in the 0.5 µm and 50 µm MP exposed groups. Additionally, both groups experienced reductions in hepatic triglyceride (TG) and total cholesterol (TCH) levels, alongside decreased mRNA expression of genes critical to lipogenesis and TG synthesis within the liver and epididymal fat, highlighting significant metabolic and microbiome disruptions.

In 2020, a researcher investigated the effects of PS-NPs on primary cells, revealing differential responses among cell types [188]. While PS-NPs exposure did not affect the viability of mouse embryonic fibroblasts (MEFs) or astrocytes, it significantly reduced viability in mixed neuronal cells. PS-NPs were found to accumulate in the cytoplasm of cells, leading to apoptosis in neurons and reactive astrocytosis in astrocytes. Furthermore, in-vivo studies by Prüst et al.,[145] and Fournier et al. [46], highlighted the migration of NPs through respiratory pathways, impacting AChE activity in rats and reaching maternal-foetal tissues during pregnancy. These findings underscore the need for further research to understand the cellular and systemic effects of micro-nanoplastics exposure. Studies have shown that micro-nanoplastics have adverse effects on various physiological systems. In another study, Choi et al. investigated the in vivo effects of NPs and coagulation-purified nanoplastics (PurNPs) on biodistribution, toxicity, and inflammatory response in ICR mice. Mice were exposed to three NPs doses (5, 25, and 50 mg/kg) and PurNPs over a two-week period. Although water consumption significantly increased in a dose-dependent manner across NPs-treated groups, other feeding and excretion behaviors showed no significant changes. Nanoplastics administered orally were found in the intestines, kidneys, and liver, with the highest accumulation observed in the intestines. Despite NPs presence in these organs, serum biochemical markers and tissue structures remained unaltered, indicating no significant toxicity or inflammatory response across the tested doses [189]. Similarly, Xiao et al. investigated the effects of PS-NPs on young mice, aged four weeks, through oral administration at doses of 0, 0.2, 1, or 10 mg/kg for 30 days. Their findings revealed that oral exposure to PS-NPs influenced the expression of genes related to mucus secretion and altered the composition of the intestinal microbiota. Interestingly, despite these molecular and microbial changes, there were no observed behavioural impairments in the young mice. Additionally, the study found no significant signs of inflammation or oxidative stress in key organs, including the liver, lungs, intestine, cortex, or serum. Pathological examinations also confirmed the absence of structural damage in these organs. Although PS-NPs did not cause immediate or evident toxicity in major organs, the study suggests that the potential toxicity of PS-NPs could vary based on factors like dosage, exposure route, and species, leaving the broader implications of PS-NP exposure in question [190].

Hu et al., observed that exposure to NPs can severely impact immune cells and reproductive health. In an allogeneic mating model, they exposed mice to 10 μm PS-MPs during peri-implantation, which led to a higher embryo resorption rate, likely due to decreased uterine arteriole count and size, which could impair blood supply to the uterus [45]. Immune disturbances were evident with reduced decidual natural killer cells, increased helper T cells in the placenta, and a shift in macrophage polarisation towards the M2 subtype, resulting in an immunosuppressive cytokine profile, thereby compromising pregnancy outcomes. Similarly, Xie et al. [191] studied PS-MP effects on male mice, finding suggested reduced sperm count and motility, higher sperm deformity rates, and decreased testosterone levels. They linked these effects to oxidative stress, which activated JNK and p38 MAPK pathways; however, these reproductive damages were mitigated when ROS was scavenged by N-acetylcysteine (NAC) and by inhibiting p38 MAPK with SB203580. Meng et al., further demonstrated that in the GIT, PS-NPs and PS-MPs aggregate, enhancing bioaccumulation and toxicity in the kidneys. Their study showed that ingestion of these particles led to significant oxidative stress, inflammation, weight loss, kidney damage, and increased mortality in mice, thus highlighting the systemic toxicity of PS-NPs and PS-MPs at different sizes [192]. Moreover, Lee et al. [193], and Fan et al. [194], reported significant visceral organ injuries in mouse and rat models, with notable effects on endpoints. Pathological examinations of internal organs revealed varying degrees of damage, particularly in the liver, kidney, and lung.

Additionally, a study conducted to investigate the oxidative stress induced by exposure to PS-NPs and the resulting physiological responses in male Wistar rats [180]. The animals were orally administered with PS-NPs at four different doses (1, 3, 6, and 10 mg/kg day) over 5 weeks. The results revealed a dose-dependent accumulation of PS-NPs in the body, accompanied by an increase in the production of reactive oxygen species (ROS). Changes in antioxidant responses, including alterations in serum CAT levels and total glutathione content, were observed, indicating a disturbance in the redox balance due to exposure.

Also, various biochemical parameters such as glucose, cortisol, lipase, lactate, lactate dehydrogenase (LDH), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), triglycerides, and urea exhibited significant increases, while levels of total protein, albumin, and globulin showed a notable decrease. In 2023, researchers showcased the disruptive impact of both PS-NPs and PS-MPs on gut barrier function and miRNA expression in exosomes, indicating significant biological repercussions [178]. They exposed Wistar rats to 50 nm PS-NPs or 5 μm PS-MPs for 4 weeks, uncovering adverse effects on intestinal barrier function and exosomal miRNA expression. The distribution of micro-nanoplastics in rats presents a multifaceted scenario influenced by factors like size and surface properties.

The findings underscored the risk micro-nanoplastics pose to various organisms, including rats, as they can infiltrate the food chain via ingestion and inhalation (refer to Table 3). Recently, research has been focused on investigating the combined toxicity of micro-nanoplastics with pre-existing xenobiotics such as heavy metals [85] (Fig. 3(b)). The investigation focused on the potential involvement of PANoptosis, a complex form of programmed cell death, in cardiac injury induced by co-exposure to PS-NPs and Cd [42]. Male mice (n = 60) were orally administered environmentally relevant concentrations of PS-MPs (1 mg/kg) and/or CdCl₂ (1.5 mg/kg) for 35 days. The study revealed significant alterations in the expression of pyroptosis, apoptosis, and necroptosis-related genes and proteins, along with impaired myocardial microstructure and growth restriction in mice. Interestingly, exposure to Cd and PS-NPs together exacerbated toxic damage, while also promoting linear ubiquitination of specific proteins in myocardial tissue. This research contributes valuable insights into the cardiotoxic effects of Cd and PS-NPs, enhances understanding of myocardial PANoptosis, and lays a foundation for further exploration of the combined toxicological impacts of PS-NPs and heavy metals (Fig. 3. (b)).

Table 3.

Distribution, bioaccumulation, effects of micro-nanoplastics in Rats.

S. No.	Animal	Type of Plastic	Particle Size (μm)	Duration	Effects	References
1	BALB/c mice	PS	5.0–5.9	Six weeks	Reduction in sperm count, mobility, and serum testosterone levels; elevation in sperm deformity rates; and heightened oxidative stress levels.	[191]
2	CD−1 mice	PE and PS	0.5–1	90 days	Enhanced toxicity towards flame retardants.	[195]
3	ICR mice	PE	∼16.9	90 days	Variations in lymphocyte subpopulations within the spleen, reductions in IgA levels among female subjects, modifications in the number of live births per dam, and alterations in pup body weight were observed.	[189]
4	ICR mice	PS	5 and 20	Four weeks	Accumulation was observed in the liver, kidney, and gastrointestinal tract, alongside instances of liver inflammation, heightened neurotoxicity markers, oxidative stress, reduction in hepatic total cholesterol and triglyceride levels, and various metabolic changes.	[184]
5	Sprague Dawley rats	PS	∼24	One-time administration	Pulmonary embolism, hypoxemia, elevated alveolar neutrophil chemotaxis, and reduced survival rates.	[196]
6	Sprague Dawley rats	PS	0.1	Fourteen days	Male rats exhibit a reduction in inspiratory time, while female rats experience a decrease in inspiratory-expiratory times and respiratory frequency in certain groups. Additionally, elevated markers of lung fibrosis and inflammation are observed among female rats.	[197]
7	Swiss mice	PE	35.5	One week	Transfer of MPs through the food chain leads to their accumulation in the liver, resulting in reduced risk assessment and defensive social aggregation in the presence of predators.	[198]
8	Wistar rats	PS	25 and 50	Five weeks	Minor alterations in neurobehavioral.	[199]
9	Wistar rats	PS	0.5	90 days	Pyroptosis and apoptosis observed within cardiac tissue	[200]

4.2. Behavioural effects in rats

Exposure to micro-nanoplastics has been linked to altered behaviour in rats, suggesting potential neurological impacts. Studies indicate changes in neurobehavioral activity, anxiety-like behaviour, and cognitive functions, raising concerns about the behavioural effects of micro-nanoplastics on rat populations. Rafiee et al., investigated the neurobehavioral effects of long-term PS-NPs exposure in rats. Despite no statistically significant behavioural effects, rats exposed to PS-NPs showed a greater number of entries into open arms in the elevated plus maze compared to controls, indicating potential behavioural alterations [199]. Additionally, Kim et al., explored ingesting NPs during early developmental stages influences social and cognitive behaviours in male mice. In their study, NPs of 100 nm in size were administered orally, allowing the researchers to assess the behavioural impact across different developmental phases. Findings revealed that exposure to NPs led to marked alterations in social behaviours, with the effects varying depending on the specific developmental period. These behavioural changes were linked to dopamine-associated neural circuits, suggesting that NPs may interfere with the neural pathways responsible for regulating social interactions and cognitive processing [201].

Mittal et al., developed polylactide-co-glycolide (PLGA) nanoparticles coated with tween 80 (T-80) to facilitate brain delivery of estradiol via oral administration. These estradiol-loaded nanoparticles were created using a single emulsion technique, with T-80 coating optimised by varying the concentration of T-80 during incubation [202]. In an ovariectomized (OVX) rat model of Alzheimer’s disease, mimicking postmenopausal conditions, the T-80-coated nanoparticles demonstrated stability in simulated gastric and intestinal fluids and showed enhanced estradiol delivery to the brain. Specifically, brain estradiol levels were significantly higher in T-80-coated nanoparticles (1.969 ± 0.197 ng/g tissue) than in uncoated ones (1.105 ± 0.136 ng/g tissue) after 24 hours at a 0.2 mg/rat dose, comparable to levels achieved via intramuscular injection (2.123 ± 0.370 ng/g tissue). This indicates that T-80 coating notably improves oral bioavailability and brain targeting of estradiol. Additionally, Jin et al., assessed the effects of chronic PS-NPs exposure on thyroid hormone levels and biochemical stress in rats. Exposed rats exhibited suppressed T3 levels, increased TSH levels, and signs of nephrotoxicity, suggesting a link between PS-NPs exposure and thyroid endocrine disruption, metabolic imbalance, and kidney injury [203].

Furthermore, a trophic transfer study demonstrated that PE-MPs can transfer through the food chain from fish to mice, resulting in behavioural changes indicative of neurotoxicity. Mice fed with MPcontaminated fish displayed impaired risk assessment, social aggregation behaviour, and anxiolytic-like behaviour, highlighting potential impacts on survival and human health concerns from consuming contaminated food sources [203]. Babaei et al., investigated the physiological responses of PS-NPs exposure in male rats. Significant correlations were found between AChE activity and various biochemical responses, suggesting potential neurobehavioral repercussions or disturbances in energy metabolism, stress responses, liver function, and kidney dysfunction. However, larger sample sizes are needed to corroborate these findings and explore additional pathways and mechanisms [180].

Recently, Guimarães et al., explored the effects of PS-NPs on male Swiss mice. They exposed the animals to different doses of PS-NPs over 20 days [204]. This exposure led to behavioural changes linked to reduced brain antioxidant activity, evidenced by lower DPPH radical scavenging activity and decreased total glutathione content. The study also observed the translocation and accumulation of NPs in the brain, suggesting a potential connection between exposure and observed effects. Another study investigated the effects of NPs and MPs on mice after ingestion. It found that NPs have a higher potential to activate gut macrophages compared to MPs, leading to reprogramming of gut interleukin-1 (IL-1)-producing macrophages due to lysosomal damage. This IL-1 signalling from the gut affects brain immunity, resulting in microglial activation and Th17 differentiation, ultimately leading to cognitive decline and impaired short-term memory in exposed mice. These studies shed light on the mechanisms of the gut-brain axis, highlighting the harmful effects of NPs on brain function and emphasising the global importance of addressing plastic pollution. Marcellus et al., further explored the neurobehavioral and neurotoxic effects of MPs in rodent models. However, their impact on cellular physiology in mammals remains uncertain [205]. In their study, neural stem cells and their derivatives were exposed to PS-NP and MPs of various sizes and concentrations, revealing significant changes in gene expression related to neuroinflammation, immunity, cell migration, and lipid metabolism.

5. Human exposure to micro-nanoplastics

Microplastics are ubiquitous environmental pollutants originating from both primary and secondary sources. Primary MPs are deliberately incorporated into products like cosmetics and cleaning agents, while secondary MPs result from the degradation of larger plastic items [206], [207]. Nanoplastics, a subset of MPs, arise from the fragmentation of larger particles or are released from sources such as electronics and paints [208]. The mechanical breakdown of macroplastics under shear forces accounts for a significant portion (70–80 %) of the total plastic released into the environment, while primary MPs contribute 15–30 % [209]. Various forms of MPs, including microfibers from textiles, fragments, pellets, foam, and microbeads, are prevalent in the environment [210]. These diverse micro-nanoplastics pose risks to human health due to potential exposure through ingestion, inhalation, and dermal contact [104], [211], [212], [213] (please refer to Fig. 4). Human exposure to MPs occurs through ingestion via contaminated food and water sources, including seafood and drinking water. Inhalation exposure arises from airborne particles released during plastic degradation, industrial processes, and surface abrasion. Skin contact presents another exposure route, notably through personal care products with microbeads or microfiber-containing fabrics. Additionally, medical procedures expose individuals to plastic products, such as surgical instruments like hip replacement implants made from various plastics and breast implants with polyurethane foam. Plastic components in medical devices like rectal and defibrillator components further highlight their importance in healthcare. Recognizing these exposure pathways is vital for developing strategies to mitigate microplastic pollution's adverse effects on human health and the environment [214] (refer to Table 4).

Fig. 4.

Sources and Accumulation of micro-nanoplastics in Human.

Table 4.

Summary of the effects of micro-nanoplastics on humans.

S. No.	Source	Models	Type of Plastic	Size	Effects	References
1	Fluorescent, non-fluorescent, carboxyl-modified and amino modified	Caco−2 cells	PS	20, 40, 100,1000, 10,000 nm	The cytotoxicity of PS micro-nanoplastics to Caco−2 cells was found to vary with concentration levels. Furthermore, photo-transformation augmented the cytotoxic effects of PS-MPs.	[232]
2	Plastic films	Caco−2 cells	PET	10–80 nm	The interaction between micro-nanoplastics and aqueous pollutants led to the formation of nanoclusters, impacting cellular metabolism and indicating potential long-term risks.	[233]
3	Normal and fluorescent PS	Caco−2 cells	PS	0.05–0.1 μm; 0.04–0.09 μm	Although micro-nanoplastics were easily uptaken by Caco−2 cells, the observed toxic/genotoxic. effects were classified as slight	[234]
4	Pristine and fluorescent nanoparticles	Caco−2 cells	PS	50 nm	Micro-nanoplastics accumulate within cells, with minimal alterations observed in various genotoxicity-related biomarkers assessed. This indicates the absence of DNA damage or oxidative stress following prolonged exposure.	[235]
5	Powder	-	PS	20–2000 nm	Studied the in vitro cytotoxicity of 13 polystyrene micro-nanoplastics (20–2000 nm) on human nasal epithelial cells (HNEpCs) at 10–1250 μg/mL concentrations. Results showed reduced cell viability, increased cytotoxicity, and induction of apoptosis and necrosis. Histological analysis confirmed the harmful effects of these nanoparticles.	[236]
6	Powder	In vivo mice model	PS	50 nm	Exposure to oral PS micro-nanoplastics led to changes in the composition of the intestinal microbiota community.	[190]
7	Pristine carboxyl-modified and amino- modified	In vivo mice model	PS	70 nm, 5 μm	The ingestion of these micro-nanoplastics led to significant alterations in gut microbiota composition.	[237]
8	Pristine and fluorescent polystyrene	In vivo mice mode	PS	5 μm	Exposure to polystyrene micro-nanoplastics resulted in changes to the diversity of gut microbiota.	[203]
9	Synthesised from styrene.	Caco−2 cells	PS	50 nm and 0.5 μm	Micro-nanoplastics exhibited low acute toxicity and were found to possess weak embryotoxic effects and no genotoxicity. While cellular uptake and intracellular accumulation were observed, micro-nanoplastics did not traverse the intestinal or placental barrier.	[238]
10	Unmodified and carboxyl modified	Small intestinal epithelium	PS	25, 100, 1000 nm	The absorption of carboxyl PS materials exhibited size dependency, particularly showing notably higher absorption at 25 nm. Moreover, carboxylated micro-nanoplastics notably diminished cell viability and heightened permeability to 3 kD dextran.	[239]

5.1. Human ingestion of micro-nanoplastics

Mounting evidence paints a concerning picture: humans might be unknowingly consuming micro-nanoplastics through various sources [104]. Studies have detected their presence in food items such as seafood, sugar, and bottled water, indicating widespread contamination. Moreover, MPs have been found in human faeces, indicating their transfer from food to the body [215]. These micro-nanoplastics are commonly found in food, drinking water, and plastic food packaging with exposure influenced by factors like age, gender, diet, and lifestyle [216]. Wildlife also ingest micro-nanoplastics, posing a threat to food safety and human diets [217]. In aquatic environments, MPs have been detected in various seafood types, with bivalve soft tissue being a major source of human exposure [160]. Studies have reported relatively low micro-nanoplastic levels in farmed bivalves [218]. Additionally, Dobrzycka-Krahel et al. provided novel insights into plastic ingestion by the invasive signal crayfish (Pacifastacus leniusculus) in the Wieprza River, which connects to the Baltic Sea [219]. Utilising FTIR for the analysis, this study was the first to document plastic particles within the stomachs of this crayfish species. Plastics ranging from 70 to 450 µm were found in 7.3 % of specimens, exclusively in crayfish residing in the river’s urbanised, downstream regions. The most commonly identified polymer was polytetrafluoroethylene (PTFE), followed by cellophane, PP, PE, PMMA, and nylon. Notably, fibres were the predominant microplastic form, indicating a higher incidence of fibrous pollutants in urban aquatic habitats.

Takeaway food consumption further amplifies the risk, with estimates suggesting significant ingestion rates [20]. Micro-nanoplastics have been identified not only in food but also in drinks and tap water, underscoring the widespread nature of this issue. Despite being in the early stages, biomonitoring efforts have detected MPs in human placentas, raising significant health concerns [86]. The ubiquity of these particles highlights the urgent need for more research and stricter regulations to mitigate their presence in the environment and food chain. The studies have also identified various types of MPs in respiratory sputum samples, with polyurethane being the most common [220]. Although in vivo studies on human toxicity from MPs remain limited, their presence in human faeces confirms that these particles do enter our bodies. Yan et al. conducted a pioneering study that compared MP levels in the faeces of patients with inflammatory bowel disease (IBD) to those of healthy individuals [221]. Results showed that IBD patients had a notably higher faecal MP concentration (41.8 items/g dry matter) compared to healthy controls (28.0 items/g dry matter). A total of 15 MP types were detected, with PET (22.3–34.0 %) and PA (8.9–12.4 %) being the most prevalent, primarily appearing in sheet and fibre forms, respectively. The study further revealed a positive correlation between MP concentrations in faeces and IBD severity, suggesting a potential link between MP exposure and IBD progression. Furthermore, research in Malaysia revealed MPs in human colostomy samples, emphasising the growing evidence of human exposure to these particles [222].

Also, various research has found MPs in the human body, with adverse effects on female reproductive health observed in animal studies. Miscarriage, affecting 15–25 % of pregnant women globally, is a significant concern [223]. PS plastic particles were detected in the villous tissues of women, particularly in those with unexplained recurrent miscarriage (RM) compared to healthy controls. Exposure to PS-NPs induced miscarriage in mice, with doses of 50–100 mg/kg being particularly impactful. Exposure to PS-NPs mechanistically induced heightened oxidative stress reduced mitochondrial membrane potential, and increased apoptosis in human trophoblast cells via the Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3 pathway. Similar effects were observed in placental tissues from PS NP-exposed mice and villous tissues from women experiencing unexplained recurrent miscarriage (RM). Supplementation with Bcl-2 mitigated apoptosis in trophoblast cells and reduced miscarriage rates in pregnant mice exposed to PS-NPs. Overall, PS-NPs activated the Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3 pathway, contributing to miscarriage. Despite this, research on micro-nanoplastics in baby food remains scarce.

In their recent research, Kadac-Czapska et al., aimed to evaluate micro-nanoplastic contamination in infant formula [224]. Thirty products underwent thorough analysis utilising advanced microscopic and spectroscopic techniques to isolate, identify, and characterise particles. MPs were detected in all samples, predominantly comprising PA, PE, and PET. These particles exhibited various forms, including fibres, fragments, and films, appearing in colours ranging from colourless to black and brown. The estimated daily intake of micro-nanoplastics for infants solely reliant on formula was approximately 49 ± 32 particles, suggesting potential health hazards. Regarding MPs in human arteries and their association with atherosclerosis, there is currently limited data [207] (refer to Fig. 5(a, b)). Addressing this gap, PY-GC-MS) was employed in this study to detect MPs in arteries with atherosclerotic plaques and plaque-free aortas. MPs were present in all 17 arterial samples, with a notably higher concentration in arteries with plaques. This indicates a plausible link between MPs and atherosclerosis in humans.

Fig. 5.

(a) Arterial sample microplastic concentration and (b) Estimation of total microplastic loads in human bodies using current and online data. Tissues used for total microplastic abundance estimation include lungs, spleen, kidney, small intestine, large intestine, and liver; tissues for microplastic mass estimation include lungs, small intestine, large intestine, and blood (Reproduced with permission from Zhu et al. [207] respectively).

Additionally, researchers employed laser direct IR spectroscopy to evaluate microplastic exposure through the respiratory and digestive systems in various human tissues [49]. MPs ranging from 20 to 100 μm were detected in all tissues, with PVC emerging as the most prevalent polymer. Notably, lung tissue displayed the highest concentration of MPs, raising concerns regarding potential health hazards associated with PVC particles, given their elevated polymer hazard index and maximal risk level.

5.2. Inhalation of micro-nanoplastics

Micro-nanoplastics can enter the human body through various pathways, with inhalation being a significant contributor. Degradation of larger plastics and improper disposal of plastic fragments create vast amounts of micro-nanoplastics that pollute these environmental compartments [225]. Additionally, synthetic clothing releases microfibers, further adding to airborne micro-nanoplastics [210]. These airborne particles range in size and concentration, with reported values between 0.3 and 1.5 fibres/m³ . Consequently, several studies have investigated the presence of micro-nanoplastics in human samples. Plastic particles of various sizes exist in the environment, contaminating soil, water, and air [84], [106], [128]. Notably, Amato-Lourenco et al., found 33 MP particles in the lung tissue of 13 individuals, including polymeric particles less than 5.5 µm and fibres ranging from 8.12 to 16.8 µm [49]. PE and PP were the most frequently detected polymers. Furthermore, Jenner et al., identified a total of 39 MP particles in lung tissue (average 1.42 ± 1.50 MP/g), highlighting significant human exposure [226]. Similarly, Huang et al., detected 21 different types of MPs in sputum samples from patients with respiratory diseases, ranging in size from 20 to 500 µm with polyurethane being the most prevalent polymer. This evidence, presented in chronological order of publication year, underscores the growing concern about human inhalation of micro-nanoplastics and the need for further research to understand their potential health implications [220]. Recently, Cao et al., investigated the impact of aged MPs on human respiratory health, focusing on their interaction with lung surfactant (LS) and oxidative damage mechanisms [227]. In vitro experiments revealed that aged MPs increased LS surface tension and reduced foaming ability, possibly due to enhanced phospholipid adsorption and protein structural changes. Aged MPs are also aggregated in simulated lung fluid (SLF), with smaller hydrodynamic diameters compared to unaged MPs. Furthermore, the presence of enduring free radicals on aged MPs prompts the generation of reactive oxygen species, resulting in lipid peroxidation and protein degradation, thereby elevating susceptibility to respiratory ailments. This research unveils the potential hazardous impact of aged MPs on the human respiratory system, underscoring the significance of comprehending the risks linked with inhaling such particles.

5.3. Micro-nanoplastics induced dermal exposure in humans

Micro-nanoplastics are increasingly becoming a concern due to their potentially detrimental effects on human health and the environment. These tiny particles can enter our bodies through various routes, with skin contact playing a significant role. Dris et al. conducted a study to examine atmospheric microplastic fallout in both urban and suburban locations. MPs were continuously collected, filtered, and examined using a stainless steel funnel under a stereomicroscope [225]. Findings revealed an atmospheric MP deposition rate ranging from 2 to 355 particles per square meter/day, with consistently higher rates observed in the urban setting compared to the suburban one. It was determined Through chemical analysis that 29 % of the fibres collected were entirely synthetic or composed of synthetic and natural materials. By estimating the weight and volume of these fibres, researchers projected that atmospheric fallout could deposit between 3 and 10 tons of microplastic fibres annually across the Paris metropolitan area, spanning approximately 2500 sq. KM.

An investigation by Duis and Coors, identified personal care products as significant contributors to environmental microplastic pollution, originating from the abrasion and fragmentation of larger plastic items [91]. Subsequent studies by Dris et al., examined microplastic presence in everyday products, such as sunscreens and face washes, further emphasising the potential for skin contact exposure [228]. During COVID-19 it was documented microplastic were released from surgical masks during the pandemic, posing additional exposure risks [229]. These micro-nanoplastics have negative impacts on sex hormone metabolism using human adenocarcinoma cells, raising concerns about health risks [230]. This chronological analysis underscores the growing evidence of human exposure to micro-nanoplastics through skin contact and other pathways. As research progresses, understanding their full implications for human health and the environment remains essential.

Recently Li et al., investigated the production and transport of MPs from protective mobile phone cases (PMPCs) during prolonged contact with the human body [231]. Over 3 months of actual use, the researchers found an average abundance of 1122 MP particles per cm² on PMPCs and 314 particles/cm² on the palm. Four main types of MPs were identified, highlighting the complex composition of PMPCs, which may originate from recycled plastics. Notably, the median sizes of MPs on PMPC surfaces and palms were 28 µm and 32 µm, respectively, smaller than reported in previous studies. The study identified ultraviolet aging and friction as primary factors contributing to MP generation during daily PMPC use. Furthermore, a regression equation and Monte Carlo simulation suggested a significant increase in MP generation after approximately 33 days of PMPC use.

6. Mirco-nanoplastics act as a carrier for other pollutants

Micro-nanoplastics, with their large surface area and hydrophobic nature, act as sponges, readily absorbing diverse contaminants from the environment [35], [240]. While Lu et al., employed inductively coupled plasma-mass spectrometry (ICP-MS, NexION 300X, PerkinElmer Inc, USA) to determine the concentration of cadmium (Cd) in the digestion solution [36], Singh et al., investigated the stability of PS-NPs under varying conditions, utilising the DLS technique [240]. The "sponge effect" alters the availability and interaction of these contaminants with organisms, potentially leading to combined toxicity. Studies have shown increased accumulation of metals like cadmium and copper in zebrafish organs when combined with MPs, causing oxidative damage and inflammation [36]. Additionally, MPs can upregulate genes related to DNA repair and detoxification in response to combined exposure with other pollutants, suggesting a complex biological response [241]. Furthermore, the numerous additives used in plastic production, including persistent organic pollutants (POPs), can leach into the environment and further contaminate MPs. These pollutants readily adsorb onto the plastic surface, creating a vehicle for their entry into marine organisms [15], [21], [242]. Studies have demonstrated the absorption of pesticides and other organic pollutants by various types of plastic films, highlighting their potential role in pollutant transport and accumulation [243]. The impact of MPs on metal adsorption is size-dependent and influenced by surface charge. While some MPs, like PE, may limit metal uptake due to their low density and limited interaction with organisms, others can enhance the bioaccumulation and toxicity of metals like cadmium and copper in various organs. Combined exposure to metals and MPs can trigger complex responses in organisms, including the upregulation of detoxification genes and the down-regulation of oxidative stress genes, highlighting the potential for combined toxicity [237]. Overall, micro-nanoplastics pose a significant threat by acting as carriers and concentrators of various contaminants, potentially leading to combined toxicity and complex biological responses in exposed organisms. Further research is crucial to understand the full extent of this issue and develop effective mitigation strategies.

7. Energy harvesting strategies

Energy harvesting is increasingly recognized as an effective alternative to traditional plastic waste production methods, which frequently result in substantial energy losses due to the improper handling of plastic waste [244]. The swift rise of micro-nanoplastics in terrestrial and marine environments poses significant risks to ecosystems and human health [245], [246]. Their widespread presence, even in isolated areas, highlights the urgent need for effective recycling techniques that incorporate energy recovery to mitigate their detrimental effects. Currently, three main strategies are being utilised for energy harvesting from plastic waste:

7.1. Biological energy harvesting

Plastic pollutants can leach chemical contaminants into the environment, leading to toxic effects. Microorganisms can colonise on the surface of micro-nanoplastics, facilitating their geographical spread and altering the physical properties of the plastics, such as increasing density and reducing hydrophobicity [247], [248]. Various microorganisms, including bacteria, fungi, algae, and viruses, are capable of degrading MPs and converting them into simpler organic compounds, which can be harnessed for energy production. This biological approach presents a potential method for recycling MPs and extracting energy by examining and optimising the functions of these microorganisms. The studies have detailed the extent of biodegradation of plastic waste by these microorganisms [249], [250].

Research highlights the potential of microorganisms for biodegradation of plastics like PET and PS. In 2011, Ribitsch et al. studied the hydrolysis of PET by Bacillus subtilis p-nitrobenzylesterase (BsEstB), noting its enhanced stability and catalytic efficiency under optimal conditions, leading to the production of terephthalic acid (TPA) and other byproducts [251]. Further investigations demonstrated that combining cutinase from Humicola insolens with MHETase from C. Antarctica significantly increased product concentrations, doubling yields compared to individual enzyme use [252], [253]. In 2017, Quartinello et al. also highlighted the potential of chemo-enzymatic treatments to recover up to 85 % TPA from PET under specific conditions [254]. Moreover, the discovery of the fungus A. beijerinckii HM121, which biodegrades PS, underscores the diversity of microbial strategies available [255]. Recent studies have focused on isolating fungi capable of degrading HDPE and other plastics, enhancing the need for optimised enzymatic processes to expedite degradation [256], [257], [258]. These findings emphasise the importance of biological methods in recycling plastic waste, particularly in marine environments, offering an eco-friendly approach to renewable energy recovery. However, the research on biological energy harvesting from marine-discarded plastics remains limited, highlighting a critical area for further exploration.

7.2. Chemical energy harvesting

Chemical methods involve breaking down plastic waste through various reactions to produce fuel or valuable chemicals. Various strategies, including mechanochemical recycling and glycolysis, are under investigation to recycle micro-nanoplastics while generating energy or other useful products. For instance, in 2014, Al-Sabagh et al. explored the glycolysis of PET using 1-butyl-3-methylimidazolium acetate as a catalyst, achieving a remarkable 58.2 % conversion of BHET with consistent reusability of the ionic liquid [259]. Additionally, Jie et al. demonstrated that a microwave-assisted method using an iron-based catalyst could efficiently extract hydrogen from plastic waste, yielding substantial amounts of hydrogen and carbon products [260]. Another innovative approach involves a heterogeneous electro-Fenton system, which effectively degrades PVC and generates various organic compounds through a series of transformations [261]. Recently, Chow et al. developed a mechano-chemical process to convert polymers like PE and PP through ball-milling, producing gases and other byproducts [262]. Despite these advancements, current recycling technologies for micro-nanoplastics are still in their early stages, and further research is essential to develop more efficient energy harvesting systems that can address the secondary pollution caused by MPs [263].

7.3. Thermal energy harvesting

Thermochemical technologies play a crucial role in converting plastic waste into energy through high-temperature chemical processes. Gasification and pyrolysis are the primary methods employed for this purpose. Gasification operates at temperatures between 500 and 1200 °C in an oxygen-controlled environment, converting carbonaceous materials into syngas, which consists of carbon monoxide, hydrogen, and other hydrocarbons [76], [77]. In 2016, Ahmad et al. reported that gasification of HDPE yielded 80.88 wt% purified liquid oil and highlighted that syngas can serve as a precursor for synthetic fuels via the Fischer-Tropsch process [264]. On the other hand, plasma gasification represents an innovative method for managing hazardous biomass waste. This technique utilises external energy to generate and maintain very high temperatures, enabling the breakdown of various types of microplastic polymers [265]. In 2017, Lu and Chiang used gasification to extract hydrogen energy and aluminium from non-recycled plastic waste containing aluminium in a lab-scale fixed bed gasifier [266]. Syngas production ranged from 4 m³ /kg to 8 m³ /kg, with an equivalent ratio increasing from 0.1 to 0.3. Higher gasification temperatures led to increased carbon monoxide and hydrogen concentrations, with syngas heating values between 0.8 and 5.1 MJ/Nm³ . The researchers reported a recovery of about 70 % of energy from the gasified plastic bags through the cold gas efficiency method, highlighting the process's effectiveness in producing hydrogen energy and recovering aluminium. In contrast, pyrolysis is a thermal degradation process that occurs in an oxygen-deficient environment, typically at temperatures from 350 to 700 °C, yielding bio-oil, pyro-gas, and biochar. In 2019, a researcher showed pyrolysis’s potential for generating liquid fuel suitable for electricity generation. Çepeliogullar and Pütün conducted a study using a fixed-bed reactor to produce liquid fuel from PET through pyrolysis. They found that the oil yield was 23.1 wt%, while gaseous products accounted for 76.9 %, with no residue remaining. The researchers noted that PET has a lower volatile content of approximately 86.83 %, which is less than that of other volatile plastics, which typically exceed 90 %, resulting in a lower liquid yield [267]. Likewise, Zhang et al. utilised a hybrid bio-thermal system for the anaerobic decomposition of plastic wastes, revealing enhanced syngas production, particularly from PS. Their findings indicated that the biochar-amended process improved methane production by up to 30 %, suggesting a positive influence on microbial pathways for gas generation. The above mentioned thermochemical processes illustrate the significant potential for converting MPs into valuable energy resources, supporting the development of sustainable energy solutions [268].

Lastly, these energy harvesting strategies offer promising solutions for managing plastic waste while recovering valuable resources. However, each method presents its own set of challenges and environmental considerations. Ongoing research aims to optimise these processes, improving their efficiency and minimising any potential negative impacts. As these technologies advance, they have the potential to significantly contribute to more sustainable plastic waste management practices and energy production.

8. Conclusion and future direction

Micro-nanoplastic pollution is a growing global issue due to the small size and large surface area of these particles, making them easily absorbed by organisms. These pollutants are widespread, entering through ingestion, inhalation, and skin contact, raising concerns about their potential to accumulate in the food chain and impact various organism and human health. Research on micro-nanoplastics is still limited, especially regarding their sources, transport, and remediation.

Studies show that micro-nanoplastics cause significant harm across various organisms, including zebrafish, rats, and humans. These effects include oxidative stress, weakened immunity, metabolic disruption, neurotoxicity, and reproductive impairments. Due to their size and surface area, they can absorb contaminants, increasing toxicity. In zebrafish, ingestion and accumulation of micro-nanoplastics can lead to decreased appetite, tissue deformation (such as in the gills), heightened oxidative stress, reduced immunity, lower reproductive rates, and alterations in gut microbiota. While, in rats/mice, micro-nanoplastics can disrupt brain function, potentially leading to neuronal death and declines in cognitive abilities and short-term memory. They are also linked to reproductive dysfunction, particularly in male mice. In humans, exposure to micro-nanoplastics has been associated with oxidative stress, lung damage, and adverse effects on sex hormone metabolism. Additionally, these tiny plastic particles may act as vectors for other toxic substances and pathogens due to their extensive surface area. This review also focuses on various methods for energy harvesting. These approaches not only address energy demands but also protect aquatic life from plastic pollution. Green technologies for energy harvesting from plastic waste are emerging, offering a sustainable solution through a circular economy. However, effective policies and business investment in recycling technologies are crucial for this to succeed.

Future research should focus on the exposure routes, toxic effects, recycling, and energy harvesting methods for micro-nanoplastics. More studies are needed on their impacts in terrestrial and atmospheric ecosystems, which remain underexplored. Global or regional perspectives are essential for accurate assessments, including quantitative data on the toxicological effects on various organisms. Research should also explore how micro-nanoplastics interact with other pollutants, as these interactions can further exacerbate ecological consequences. Ultimately, addressing micro-nanoplastic pollution requires coordinated efforts from governments, businesses, and the scientific community, with a focus on sustainable solutions and effective waste management strategies.

In summary, the most crucial unanswered inquiries encompass the following key areas:

• •Long-term assessments across species for human health relevance
• •Establishing standard protocols for analysis and exposure assessment (ingestion, inhalation)
• •Investigating toxicokinetic and toxicity impacts on food and water sources.
• •Developing innovative sensor technologies for real-time monitoring.
• •Conducting food safety studies on contaminated seafood and water consumption.
• •Various recycling techniques
• •Government policies addressing micro-nanoplastics waste

As plastic proliferation increases, further research on human exposure, causative factors, and impacts of micro-nanoplastics is crucial for effective risk assessment, ecosystem comprehension, and health outcomes. The expeditious implementation of plastic waste reduction policies at national and international levels by policymakers is imperative.

Funding

Received no specific funding.

CRediT authorship contribution statement

Saurabh Shukla: Writing – review & editing, Writing – original draft, Supervision, Investigation, Data curation, Conceptualization. Sakshum Khanna: Writing – review & editing, Writing – original draft, Investigation, Conceptualization, Supervision, Data curation. Kushagra Khanna: Writing – review & editing, Conceptualization.

Declaration of Competing Interest

I, Dr. Saurabh Shukla (Corresponding Author), on behalf of all authors, declare that the authors have no conflict of interest to declare. However, Dr. Sakshum Khanna, one of the authors, is currently employed by Elsevier, Relx Pvt Ltd. Dr. Khanna confirms that this research was conducted before their employment at Elsevier and that the peer review process was conducted fully independently of this author

Data availability

No data was used for the research described in the article.