Sarhan Rashid Sarhan¹,  Shrooq Jaber Jassim², Ghassan Jabar Khalaf³  and Asmaa Khadhim Chafla⁴

¹Department of Basic Sciences, College of Dentistry, Wasit University, Wasit, Iraq

²Department of Nursing , Medical Technical Institute, Middle Technical University, Baghdad, Iraq

³Medical Laboratories Techniques Department, College of Health and Medical Techniques, University of  Kut, Wasit, Iraq.

⁴Department of Cosmetic and Laser Techniques, College of Medical and Health Techniques, University of Kut, Wasit, Iraq.

Corresponding Author E-mail: salzaiyaadi@uowasit.edu.iq

DOI : https://dx.doi.org/10.13005/bpj/3284

Abstract

Nanoplastics, defined as plastic particles less than 1000 nm in size, are emerging environmental contaminants of global concern. Their minute size allows them to penetrate biological barriers, potentially leading to bioaccumulation and toxic effects in a wide range of organisms. This systematic review aims to synthesize current knowledge on the toxicity and bioaccumulation of nanoplastic pollutants, focusing on their interactions with biological systems and the implications for environmental and animals and human health. Following PRISMA guidelines, a comprehensive search was conducted across PubMed, Scopus, and Web of Science for studies published between January 2010 and Sept 2025. Eligible studies reported experimental data on the bioaccumulation and/or toxicological effects of nanoplastics in vivo or in vitro. Out of 3128 initially identified records, 62 studies met inclusion criteria. Evidence shows that nanoplastics are capable of crossing cellular membranes, accumulating in tissues including the gut, liver, brain, and reproductive organs. Toxicological outcomes include oxidative stress, inflammation, genotoxicity, neurotoxicity, and reproductive impairment, with effects often dose-, size-, and surface chemistry-dependent. We concluded that the bioaccumulation and toxicity of nanoplastics have been well-documented in aquatic species and mammalian models, raising significant concerns about long-term environmental and health impacts. Further studies are needed to assess chronic low-dose exposure, human relevance, and mixture effects with other contaminants.

Keywords

Bioaccumulation of Polystyrene Nanoplastics; Endocytic Uptake of Nanoplastics; Nanoplastic-Induced Oxidative Stress; Nanoplastic Toxicodynamics; Organ-Specific Nanoplastic Retention

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Copy the following to cite this article: Sarhan S. R, Jassim S. J, Khalaf G. J, Chafla A. K. Toxicity and Accumulation of Nanoplastics Materials: A Review of Experimental Evidence Across Biological Systems. Biomed Pharmacol J 2025;18(4).

Copy the following to cite this URL: Sarhan S. R, Jassim S. J, Khalaf G. J, Chafla A. K. Toxicity and Accumulation of Nanoplastics Materials: A Review of Experimental Evidence Across Biological Systems. Biomed Pharmacol J 2025;18(4). Available from: https://bit.ly/3MGVbwK

Introduction

Plastic pollution has emerged as a global environmental crisis, with increasing attention being directed toward micro- and nanoplastics due to their widespread presence and potential biological effects. Nanoplastics (NPs), defined as plastic particles less than 1000 nm in size, are particularly concerning due to their high surface area-to-volume ratio, environmental persistence, and ability to interact with biological molecules and systems. Due to their small size, nanoplastics can pass across biological barriers, e.g. the gut epithelium, blood–brain barrier, but also placental tissues. Upon internalisation, they can have the ability to be distributed to different organs and trigger a wide range of cellular and molecular responses, from oxidative damage and inflammatory processes to genotoxicity and changes in gene expression.¹ Since nanoplastics can adsorb environmental contaminants and biomolecules, they can also serve as vectors for poisoning that extends well beyond the chemistry of these particles.² Despite increasing recognition of their potential harm, a comprehensive understanding of nanoplastics’ toxicological profiles and bioaccumulation dynamics across species and systems remains limited. Several factors, such as particle size, polymer type, surface charge, and environmental aging, influence nanoplastic behavior and biological impact.³ For instance, the polymer type can significantly affect the degree of toxicity, with some polymers more prone to leaching harmful additives than others. Similarly, the surface charge of nanoplastics can determine how they are taken up by cells and tissues. This is especially relevant in the context of marine and terrestrial organisms, where nanoplastics can have different effects on bioaccumulation and health. ^4,5 Given the widespread presence of nanoplastics in the environment and their potential to accumulate in living organisms, there is a pressing need for a more comprehensive understanding of their toxicological profiles. ⁶ This systematic review aims to bring together current research on the toxicity and bioaccumulation of nanoplastics, with a particular focus on experimental studies that provide mechanistic insights into their biological effects. ⁷ By examining patterns across studies, identifying critical knowledge gaps, and considering the variables that influence outcomes, the review aims to inform future research and regulatory efforts aimed at assessing the risks associated with nanoplastic pollutants.

Materials and Methods

Protocol and Registration

This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol was not registered in PROSPERO.

Eligibility Criteria

Inclusion Criteria Exclusion Criteria

Studies evaluating toxicity or bioaccumulation of nanoplastics Reviews, editorials, commentaries.

In vivo or in vitro experimental studies

Studies not involving nanoplastics (<1000 nm)

Publications in English Studies focused solely on microplastics (>1000 nm)

Published from January 2010 to Sept 2025 Studies lacking toxicological or accumulation outcomes.

Information Sources

Databases searched: PubMed, Scopus, and Web of Science.

Search period: January 2010 – Sept 2025.

Search Strategy (example for PubMed).

Study Selection

After removing duplicates, two independent reviewers screened titles and abstracts. Full texts of potentially eligible studies were assessed for final inclusion. Discrepancies were resolved through discussion.

Data Extraction

From each included study, the following data were extracted:

Author(s), Year

Nanoplastic type and size

Model system (species or cell type)

Exposure dose and duration

Accumulation site(s)

Toxicity endpoints

Key findings

Risk of Bias Assessment

Despite rapid growth, nanoplastics toxicology studies face several biases that may affect interpretation and risk estimation.

Synthesis Methods

Qualitative synthesis is one of the crucial means (in the systematic review) for synthesizing and interpreting complex data in the form of presentation, especially in those areas where quantitative metrics fail to provide a comprehensive view of evidence coverage. This strategy goes beyond superficial summarizing by noticing patterns, themes and gaps in a series of studies and therefore delivers advanced understanding of complex phenomena. For example, Qualitative synthesis is very important in Public health research (where socio-cultural issues are just as relevant as metrics). (The Thomas & Harden, p. 18) Additionally, it is a vital part of attempting to influence policy by drawing together disparate evidence and synthesising integrated insights.⁸ Controls to ensure there is originality and, of course maintaining ethical standards it is wise that anti-plagiarism should be followed, primary sources citations and the use of standardization frameworks such as PRISMA to promote academic transparency should be applied. The use of qualitative syntheses prudently will help researchers expand evidence based processes and uphold high academic standards.

Results

Study Selection

Using a comprehensive search on PubMed, Scopus, and Web of Science databases between January 2010 and Sept 2025 returned 3,128 articles. After removal of duplicates (n=364), 2764 records were screened using titles and abstracts. Of these 152 articles were screened for the full text evaluation. Ultimately, 62 studies qualified the inclusion criteria and were included for the final analysis. Causes of exclusion were incorrect particle size (> 1 µm), lack of toxicity or bioaccumulation endpoints or use of review-only data.

The selection process is shown in PRISMA 2020 compliant flow diagram.⁸ (Figure 1).

Figure 1: PRISMA Flow Diagram Click here to view Figure

Reasons for exclusion included lack of relevant outcomes or incorrect particle size classification. (Table 1) shows a representative summary data.

Tables 1: Representative data summary.  

No	References	Model	Exposure Route	Main Finding
1	Van Cauwenberghe & Janssen 9	Humans seafood consumers	Ingestion	Bioaccumulation through seafood consumption.
2	Monteiro-Riviere et al10	Human skin )theoretical(	Dermal contact	Limited penetration possible in damaged skin.
3	Tabl et al  11	Rodents	Oral ingestion	Accumulation in liver, hepatocyte vacuolization.
4	Lv et al  12	Male rats	Oral ingestion	Testicular accumulation and DNA damage.
5	Zhang et al  13	Mice	Oral ingestion	Intestinal barrier disruption and dysbiosis.
6	Ramsperger et al14	Human cell lines	Exposure to charged PS-NPs	Positive charges increased cytotoxicity.
7	Rai et al 15	Environmental PS-NPs	Weathering	Aging increased pollutant adsorption and toxicity.
8	Schwaferts et al16	Published studies	Literature review	Bias towards reporting polystyrene data.
9	Lehner et al  17	Research community	Protocol variation	Lack of consistent particle characterization.
10	Prüst et al 18	Animal models	Chronic ingestion	Limited multigenerational exposure studies.
11	Dris et al19	Indoor environment	Airborne exposure	Airborne fibers detected indoors.
12	Vianello et al20	Industrial workers	Airborne exposure	Occupational exposure risks highlighted.
13	Koelmans et al21	Research	Experimental setup	Need for real-world concentration studies.
14	Lehner et al17	Research standards	Study design	Urgent need for standardized NP characterization.
15	Liu et al22	Human inhalation models	Airborne	Need for inhalation models emphasized.
16	Sendra et al23	Biological systems	Exposure analysis	Application of omics to reveal mechanisms.
17	Wang et al24	Environmental interactions	Combined exposures	NPs can synergize with pollutants.
18	Baudrimont et al25	Marine ecosystems	Environmental monitoring	Nanoplastics should be contaminants of concern.
19	Fagundes et al26	Humans	Policy perspective	Importance of monitoring cumulative exposure.
20	Nene et al27	Food, water, biological samples	Analytical methods	Need for detection methods emphasized.
21	Pitt et al28	Multispecies models	Overall accumulation	Nanoplastics are bioavailable, bioaccumulative, and toxic.
22	Wu et al29	Aquatic, mammalian, cellular	General findings	Consistent evidence across systems.
23	Lin et al30	Multiple systems	Cellular mechanisms	Oxidative stress, inflammation, apoptosis central

Characteristics of Included Studies

Among the 62 studies, the majority focused on polystyrene nanoplastics (PS-NPs), primarily due to their commercial availability and consistent particle size. The remaining studies investigated other polymers such as polyethylene (PE), polypropylene (PP), and polyvinyl chloride (PVC) as shown in figure 2.

Figure 2: Distribution of Study Focus. This figure chart illustrates the number and percentage of studies focusing on polystyrene nanoparticles (PS-NPs) compared to other polymers such as polyethylene (PE), polypropylene (PP), and polyvinyl chloride (PVC). Click here to view Figure

Model organisms included

Figure 3 represent the following items

Aquatic invertebrates (e.g., mussels, Daphnia, copepods).

Fish models (zebrafish, medaka).

Mammalian systems (mice, rats, human cell lines).

Exposure routes were predominantly oral ingestion in aquatic and mammalian models, whereas direct incubation was common in in vitro cell cultures. Exposure durations ranged from 24 hours (acute exposure) to 90 days (chronic exposure) across studies, with doses spanning 0.01 μg/L to 1000 mg/kg body weight.

Bioaccumulation of Nanoplastics Across Biological Systems

Aquatic Organisms

Nanoplastic accumulation was consistently observed in aquatic species. Mussels exposed to PS-NPs demonstrated particle deposition in the digestive gland and gill tissues, leading to histopathological alterations. ^31,32 Similarly, zebrafish larvae ingested PS-NPs of <100 nm, with particles translocating from the gut lumen into the liver and brain tissues. ^28,33 Notably, Daphnia magna accumulated PS-NPs within their digestive tract after 48-hour exposure, impacting nutrient absorption and mobility. ³⁴

Mammalian Models

Rodent studies revealed systemic distribution of orally administered PS-NPs. After 28 days of exposure, mice exhibited nanoplastic accumulation in the liver, kidneys, and reproductive organs. ^35.36 In a notable study by Deng et al ³⁷ fluorescently labeled PS-NPs crossed the intestinal barrier and were detected in the spleen and bloodstream, indicating potential systemic exposure. 

Figure 3: Biological Models Used in Studies. The figure presents the number and percentage of studies employing different biological models: aquatic invertebrates (e.g., mussels, Daphnia, copepods), fish species (e.g., zebrafish, medaka), Click here to view Figure

Human Cell Lines

Research in vitro using human intestinal (Caco-2) and lung epithelial (A549) cells has shown that PS-NPs are markedly endocytosed in cells. It was identified that these particles would localize inside lysosomes and lead to vesicle accumulation. ^16,38 In addition, exposure to nanoplastics resulted in disruption of tight junctions in Caco-2 monolayers which meant that there is compromised intestinal barrier function. ¹⁶

Toxicological Effects of Nanoplastics

The (figure 4) summarizes all the following toxicological effects caused by nanoplastics

Oxidative Stress and Inflammation

Oxidative stress was indicated as the most common toxicological effect. Both aquatic species show increased lipid peroxidation and inflammatory markers ³⁹ as proven by ⁴⁰ has also been observed in mammalian models. ^35,36 The treatment of zebrafish embryos with PS-NPs led to triggering an Nrf2 pathway, indicating that the cells started to implement systems of oxidative defense. ⁴¹

Neurotoxicity

Numerous investigations documented neurotoxic consequences.  After oral exposure PS – NPs were found in brain tissue with elevated proinflammatory cytokine levels and neuronal apoptosis, respectively. ⁴² Zebrafish larvae, which were given PS-NPs, showed aberrant behaviors including hyperactivity and failure to avoid predators.^28,43

Figure 4: Frequency of Toxic Effects Observed. This figure shows the distribution of toxic effects reported across studies, including oxidative stress, neurotoxicity, reproductive toxicity, and immunotoxicity. Click here to view Figure

Reproductive Toxicity

The chronic consumption of PS-NPs in male rats influenced the testicles” histopathology, and loss of sperm motility with the number of sperm. ⁴⁴ In the transplacental transfer of nanoplastics has been shown with zebrafish and hypothesized in models of mice that potential effects on fetal growth and development have been proposed. ^{28, 45}

Immunotoxicity

PS-NPs affected the hemocyte function of mussels and hemocytes’ phagocytic activity and destabilization of lysosomal membrane. ^31,46 Similarly, macrophage cell lines from humans exposed to nanoplastic revealed secretion of proinflammatory cytokine and phagosome dysfunction. ⁴⁷

Human Exposure Pathways to Nanoplastics

In (figure 5) we summarized the human exposure route to nanoplastics

Ingestion

The ingestion route is still the leading exposure way for humans to nanoplastics. Research on drinking water, seafood, and salt has reported PS-NPs.^48,49 Further analysis of bottled water revealed the fact; the water contains up to 10⁴ particles/ L, including particles of nano-meter size.⁵⁰  Seafood consumption, especially mollusks and crustaceans, is a major source of dietary exposure. ⁹ Mussels and oysters have shown bioaccumulation of NPs in their tissues, raising concerns over trophic transfer to humans ^31,51

Figure 5: Prevalence of Exposure Routes. This figure shows the frequency and percentage of studies investigating various exposure routes to nanoparticles, including oral ingestion, inhalation, and dermal exposure. Click here to view Figure

Inhalation

Indoor air contains micro- and nanoplastic particles, primarily originating from synthetic textiles and household dust. ⁵² Dris et al., reported airborne synthetic fibers in Parisian apartments, suggesting that inhalation could represent a significant, yet understudied, exposure route.¹⁹

Workplace exposure is of particular concern for industries involving plastics manufacturing, recycling, or textiles, where airborne nanoplastics are more concentrated.²⁰

Dermal Exposure

Although the skin acts as an effective barrier, damaged or compromised skin may allow limited penetration of nanoplastics. Evidence from nanoparticle research suggests that particles below 100 nm could potentially cross the stratum corneum under certain condition. ¹⁰ Nonetheless, evidence derived experimentally from nanoplastics are few, and further studies are needed.¹

Organ-Specific Distribution Patterns

The (figure 6) represent frequency of organ accumulation sites

Liver

Based on a few studies, the liver is an important area where nanoplastics accumulate. ³⁷  Including hepatic cell vacuolization, inflammatory disorders, and increased serum liver enzymes, the structural alterations caused by hepatic accumulation include. ^35,44 Oxidative stress as well as Kupffer cell activation commonly reported causes of disorders of the liver. ⁵³

Brain

PS-NPs demonstrated permeation across the barrier separating blood and brain in zebrafish and rodents. ^28,42  Nanoplastics have inflicted oxidative damage, inflammation of neurons and neurological conditions in the brain such as poor memory and movement. ^41,18

Reproductive Organs

Accumulation of PS-NPs in male rat testes caused oxidative DNA damage and reduced fertility and destruction of seminiferous tubules.⁵⁴ Although further studies are still needed, nanoplastics have been associated with disrupted steroidogenesis and ovarian failure in female animals; although further studies are still needed, nanoplastics have been associated with laboratory animals female ovaries failure.⁴⁵

Figure 6: Organ Accumulation Sites (Frequency). The figure details the number and percentage of studies reporting nanoparticle accumulation in various organs, including liver, brain, reproductive organs, and gastrointestinal organs. Click here to view Figure

Gastrointestinal Tract

The intestinal cells and gastrointestinal lumen were the most common post-oral ingestion locations of nanoplastics. ^16,42 Commonly reported results were intestinal villi damage, modification of tight junction proteins (in the form of occludin and claudin-1), and gut microflora dysbiosis.^42,55

Influence of Particle Size, Surface Chemistry, and Aging

While in (figure 7) summarized the particles Size and Toxicity Relationship

Size-Dependent Uptake and Toxicity

Small nanoplastics (smaller than 100nm) displayed increased toxicological strength, bio-distribution and cellular entry, compared to larger nanoplastics (>500 nm). ^35,23 Increased surface-to-volume ratios and enhanced endocytic routes are probably the leading reasons behind this size-sensitive effect.⁵⁶

Figure 7: Size-dependent Uptake and Toxicity Prevalence. This figure shows the number and percentage of studies analyzing uptake and toxicity based on nanoparticle size ranges: less than 100 nm, 100–500 nm, and greater than 500 nm. Click here to view Figure

Surface Charge and Functionalization

Particle behavior was greatly influenced by the surface chemistry. Analyzing their neutral or even negatively charged versions, positively charged PS-NPs were more cytotoxic and adherent to the membranes of cells. ¹⁴

Functionalized nanoplastics change of biological distribution patterns urged the need for particle characterization in toxicity research (such as carboxylated or aminated). ⁵⁷

Environmental Weathering and Aging

The surface characteristics of nanoplastics were changed by environmental aging caused by UV light, mechanical abrasion, and biofouling, which frequently increased their toxicity. ⁵⁸ According to Wang et al., aged PS-NPs demonstrated an enhanced ability to absorb organic contaminants and heavy metals, which could result in additive or synergistic harmful effects ⁴⁵ as shown in (figure 8).

Common Mechanisms of Nanoplastics-Induced Toxicity

Constant toxicity mechanisms were found in several biological systems:

Oxidative stress: breakdown of the antioxidant system and increased generation of ROS.^35,39

Inflammation: Elevated levels of inflammatory cytokines, including TNF-α and IL-6, are indicative of inflammation. ^31,16

Genotoxicity: chromosomal abnormalities and DNA fragmentation seen in aquatic animals and cell lines.⁴⁰

Apoptosis: After cellular exposure, caspase-dependent apoptotic pathways are activated.^42,45

Figure 8: Effects of Environmental Weathering on Nanoparticles. The figure depicts the number and percentage of studies reporting effects of environmental weathering aspects such as UV radiation, biofouling, and mechanical abrasion on nanoparticles. Click here to view Figure

Practical Implications

Environmental and Ecological Policy

There is evidence to justify the inclusion of nanoplastics in ecosystem pollution risk analyses.  Nanoplastics identification should be regulated by regulatory agencies for environmental monitoring, especially in freshwater and marine environments. ²⁵

Public Health and Food Safety

World Health Organization and Food and Drug Administration must focus their priority on developing threshold exposure limits and analytical methods eyes to eyes to the identification of NPs in the waters for drinking and aquaculture.^59,60 

Biomedical Relevance:

Findings such as the ones reported by Ding et al³⁵ may be associated with fertility, cancer and chronic diseases implications. There is an immediate need of longitudinal epidemiological studies for determination of risk.

Technological and Waste Management Innovations

The emerging indications of NP formation during heating plastic containers over microwave⁶¹ underlines the need for material innovation and waste minimizing approaches.

Qualitative Synthesis

This synthesis draws evidence from 52 studies to assess patterns of nanoplastic bioaccumulation and toxicity in biological systems qualitatively. Below the trends, mechanisms and organ specific effects are classified as following.

Uptake Routes and Translocation

In various studies, it was noted that nanoplastics breached biological barriers and were translocated systemically.

Gastrointestinal absorption

Oral exposure models ³⁵ demonstrated uptake of PS-NPs through endocytosis or paracellular transport in intestinal epithelium. In vitro studies with Caco-2 cells ¹⁶ showed tight junction disruption facilitating translocation.

Respiratory exposure

Although less studied, inhalation models suggest nanoplastics can deposit in alveoli, enter circulation, and reach secondary organs. ⁵³

Maternal transfer

Zebrafish studies reported maternal-fetal transfer of nanoplastics to embryos ²⁸, indicating developmental vulnerability.

Organ-Specific Bioaccumulation Patterns

Nanoplastics showed clear tissue tropism in both aquatic and terrestrial models:

Liver: Frequently identified as a primary accumulation site due to its role in detoxification. ³⁶ Hepatic histopathology often included necrosis, vacuolization, and inflammation.

Brain: Several studies confirmed blood–brain barrier penetration. In zebrafish and rodents, this led to neuroinflammatory responses and behavioral deficits. ²⁸

Gonads: Testicular accumulation in male rats caused spermatogenic disruption and oxidative DNA damage. ³⁶

Digestive gland/gut: Marine mussels accumulated PS-NPs in their digestive glands, leading to digestive stress, lysosomal dysfunction, and immunosuppression. ³¹

Common Mechanisms of Toxicity

Oxidative stress and inflammation were the most frequently reported mechanisms across all taxa:

PS-NPs generate reactive oxygen species (ROS), leading to mitochondrial dysfunction, lipid peroxidation, and DNA fragmentation.

Inflammatory markers (e.g., IL-6, TNF-α) were elevated in several models following nanoplastic exposure. ¹⁶

Behavioral and Neurodevelopmental Effects

In zebrafish, larval exposure resulted in hyperactivity, abnormal swimming patterns, and reduced learning capacity.²⁸

Rodents exposed prenatally or perinatally exhibited neuroinflammation and altered neurotransmitter levels, though this area remains underexplored in humans.

Immunological and Cellular Effects

Marine invertebrates exposed to PS-NPs showed disrupted hemocyte functions, lysosomal membrane destabilization, and immune suppression.³¹

In vitro studies reported dose-dependent cytotoxicity in human cell lines, especially those related to the gut, kidney, and immune system.³⁵

Influence of Particle Characteristics

Size: Particles <100 nm showed higher cellular uptake and toxicity due to enhanced surface reactivity and translocation capability.

Surface charge and functional groups also modulated uptake and interactions with cellular membranes, though data remain inconsistent.

Aging and weathering in the environment altered surface chemistry, increasing toxicity due to co-contaminant adsorption.⁵⁷

Discussion

This comprehensive review’s conclusions show that nanoplastic contaminants, especially those based on polystyrene, consistently show a capability for bioaccumulation and toxicity in a variety of biological systems.  Since nanoplastics are small, they can be absorbed through a variety of pathways, such as ingestion, inhalation, and possibly skin penetration. This enables them to move across biological membranes and build up in vital organs like the liver, brain, kidneys, and gonads.^28,35,36

Bioaccumulation Mechanisms and Tissue Distribution

The reviewed research indicates that both marine and terrestrial organisms can accumulate NPs.  Particles are found to be accumulated in the digestive system, gills, or digestive system glands of marine species, including zebrafish and mussels, where often uptake occurs through ingestion or filtration. ^{31, 28} Nanoplastics penetrate the intestinal wall passage and find distribution all over the mammalian body, especially in rodents.  Importantly, several studies have indicated that nanoplastics can penetrate the placental-blood and/or blood– brain barrier, that suggests possible long-term neurological and developmental needs for consideration. ²⁸ Particle size, surface charge, hydrophobicity, and environmental aging are among some of such variables that influence these patterns.  Due to their improved cellular uptake mechanisms, including endocytosis and passive diffusion; smaller particles (under 100 nm) generally provide higher absorption tendencies and a broad tissue distribution. ¹⁶

Toxicological Profiles

While toxin results were different in different models, mechanistic pathways were similar in all the models.  The most common observation was oxidative stress, which was often associated with cellular death, DNA damage and inflammatory reactions. ^35,16  Investigations by Chi et al. (2025) have revealed that nanoplastics would result in immunotoxicity in marine invertebrates through the disruption of the stability of the lysosomal as well as immunological functions. ³¹ Testicular degeneration and mantle cells were a testicular toxicity in mammals, which may suggest the endocrine-disrupting effects. 36 Also, neurotoxic effects such as behavioral aberrations and neurodevelopmental perturbation were highlighted in studies performed in neuronal models and early life phases. These effects were most likely associated with oxidative stress and neuroinflammation. ²⁸

Biases, Limitations, and Research Gaps

There are found numerous limitations have been found in the existing study on nanoplastics, even though there is an increasing number of studies.

Selection and Reporting Bias

Since their accessibility on the market and practicalities of packing, polyethylene or polypropylene, are not researched. ²¹ Consequently, the toxicity characteristics of other polymers such as polyethylene or polypropylene are not well established.  Moreover, there are increased rates of positive findings regarding the toxicity of nanoplastics, which could lead to a publication bias and overestimation of dangers. ²¹

Standardization Issues

The lack of standardized procedures for particle characterization/exposure models/endpoint measurements is a major limitation in the research of the toxic effects of nanoplastics. ⁶²  Cross-study comparatives are limited by the variety in particle size, surface charge, aging state and methodology of experiments.  In addition, many studies employ exposure concentrations that are significantly higher than what will be legally acceptable in the environment, making them less ecologically relevant. ²¹

Underrepresentation of Inhalation and Dermal Studies

There are drastic inhalation and external exposure models in the majority of existing data, but these come from the ingestion exposure routes only. ^44,20 Given that indoor and urban environments have been found to include airborne nanoplastics. ^19,20 This gap is crucial.

Limited Chronic and Multigenerational Data

There is a scarcity of long-term, low-dose, chronic exposure studies that reflect real-world exposure scenarios.¹⁸ Similarly, very few studies have investigated transgenerational effects, although initial evidence suggests maternal transfer and developmental toxicity are plausible.²⁸

Future Research Directions

To advance understanding and inform risk assessments, future research should prioritize

Standardized Nanoplastic Characterization: Including size distribution, surface chemistry, and agglomeration behavior under exposure conditions.⁶²

Environmentally Relevant Exposure Levels: Adopting concentrations that mirror real-world conditions.²¹

Inhalation and Dermal Exposure Models: Especially for occupational and indoor exposure settings.^44,20

Chronic, Low-Dose, and Multigenerational Studies: Evaluating subtle or delayed effects, especially on neurodevelopment and reproduction.¹⁸

Multi-omics Approaches: Utilizing transcriptomics, proteomics, and metabolomics to uncover molecular mechanisms.³³

Co-exposure Scenarios: Investigating how nanoplastics interact with chemical contaminants such as heavy metals, pesticides, or pharmaceuticals.⁴⁵

Practical Implications for Environmental and Human Health

Given the broad distribution of nanoplastics and their demonstrated biological effects, precautionary measures are warranted.

Environmental monitoring programs should include nanoplastics as contaminants of emerging concern, particularly in marine ecosystems.²⁵

Public health policies must address potential dietary and inhalation exposures, considering cumulative lifetime exposure.⁶⁰

Regulatory agencies should also develop standardized detection methods for nanoplastics in food, water, and biological samples⁵⁹

Key findings of this systematic review include:

Nanoplastics are capable of crossing biological barriers and accumulating in vital organs such as the liver, brain, and gonads.

Major toxicological mechanisms include oxidative stress, inflammation, genotoxicity, and apoptosis.

Smaller-sized particles and those with specific surface charges exhibit greater bioactivity.

Human exposure through ingestion and inhalation is plausible and likely widespread.

Significant research gaps exist, particularly regarding chronic low-dose exposures and inhalation risks.

Given the pervasive nature of plastic pollution and the emerging evidence on nanoplastics’ biological effects, precautionary approaches and strengthened regulatory frameworks are urgently needed to mitigate potential risks to environmental and human health.

Gaps and Limitations

Several limitations exist in current nanoplastics research

Lack of standardized testing protocols for nanoplastic toxicity and detection methods

Inconsistency in particle characterization, including purity, surface chemistry, and agglomeration behavior

Limited long-term and chronic exposure data, especially at environmentally relevant concentrations

Underrepresentation of co-exposure studies involving chemical contaminants or biological agents

These gaps hinder effective risk assessment and regulatory development.

Conclusion

This systematic review highlights the growing body of evidence demonstrating that nanoplastics, particularly polystyrene nanoplastics, can be taken up and bioaccumulated by a wide range of organisms, from aquatic invertebrates to mammals. Once internalized, these particles are capable of translocating to critical organs, including the liver, brain, reproductive organs, and gut, where they exert toxic effects through oxidative stress, inflammation, and cellular damage. The reviewed literature clearly demonstrates that nanoplastics can bioaccumulate and exert toxic effects across biological systems. Human exposure, though still under-characterized, is a credible concern via ingestion and inhalation. Future work must mitigate biases, improve model relevance, and link environmental data with clinical outcomes. Interdisciplinary collaboration and policy reform are essential to address this silent, microscopic threat to health and ecosystems.

Acknowledgement

The author extends sincere gratitude to Dr. Ghasan Jabar for his valuable assistance in English proofreading, enhancing the clarity and readability of this review. Appreciation is also extended to Almahdi Office for their support in preparing the review’s outlines 

Funding Source

The authors  received no financial support for the research, authorship, and/or publication of this article. 

Conflict of interest

The authors do not have any conflict of interest 

Data Availability Statement

This statement does not apply to this article

Ethics Statement

This review did not involve human participants, animal subjects, or any material that requires ethical approval.

Informed Consent Statement

This study did not involve human participants, and therefore, informed consent was not required

Clinical Trial Registration

This research does not involve any clinical trials

Permission to reproduce material from other sources

Not Applicable

Author Contributions

• Shrooq Jaber Jassim   conceived and planned the experiments carried out the methodology.
• Asmaa Khadhim Chafla and Ghassan Jabar Khalaf  planned and carried out the simulations and contributed to qualitative analysis.
• Sarhan Rashid Sarhan contributed to the interpretation of the results, took the lead in writing the manuscript. All authors provided critical feedback and helped shape the research, analysis and manuscript

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