Journal of Entrepreneurial Health Sciences and Innovation (JEHSI)™

Global Health and Environmental Impact of Plastics: The Amicrobial "Silent Pandemia"

Dr Gabriel Pulido-Cejudo^1,2*
Peter Humphries²
Dr Bratati Kar^1,2
Kaylee Mak-Lin¹
Laura Camila Peñuela Cárdenas¹
LuAnn Buechel³
Dr Khadija El Abdaimi^1,2
1International Centre for Advancement of Health Regional Innovation and Science, ICAHRIS Research
^*corresponding author, gabriel.pulido-cejudo@icahris.org
²Canadian Federation of Breast Diseases, CFBD
³ICAHRIS Research External Collaborator, Reineck Memorial Woods

Abstract

From the inception of plastics, emerging as early as 1856, to the full industrial manufacturing of the most currently used plastics such as polyvinyl chloride (PVC) in 1926, low-density polyethylene (LDPE) in 1939, high-density polyethylene (HDPE) in 1955 and polypropylene (PP) in 1957, the estimated global production of plastics in 2024 attained 460 million metric tonnes. This contributed to an additional 220 million metric tonnes of plastic waste already accumulated for centuries in global environments.

To date, all forms of life, from all kingdoms, have been exposed to plastics, nano (0.001-1µm), micro (1µm-5mm), meso (5mm-25mm) and macroplastics (>25mm), as they can be found within the deepest sediments of the sea to the Earth's stratosphere. They are perniciously present in water, air and most likely in all terrestrial and marine food webs. Concerning global health, sustained exposure to plastics, micro and nanoplastics (MNPs) have been associated with the onset of musculoskeletal, cardiovascular, respiratory and neurodegenerative diseases, cancer and immune and inflammatory disorders. They have been found in primary organs of the digestive, respiratory, nervous, cardiovascular, lymphatic and urinary systems. Their presence in temporary organs such as placenta and fetal meconium signals a deleterious generational impact in the health of humans and wildlife.

In this context, common effects of MNPs involve an enhanced production of reactive oxygen species (ROS), namely superoxide, hydrogen peroxide, hydroxyl radical, singlet oxygen and peroxynitrite, sustained inflammation as well as behavioural disorders. We postulate that human microbiome nNE biogenic clones may attenuate MNPs-induced inflammation through modulation of alkaline phosphatase and lactate dehydrogenase activities. This might be rendered possible though the role of lactate production and IL 17 reprogramming of CD4+T cells in inflammation and / or on their putative role in reversing MNP-induced dysbiosis offering a promising tool to address some of the deleterious health effects of sustained exposure to MNPs.

Interestingly, a preliminary non-quadrant archived census from 2018-2024 performed within Reineck Memorial Woods, a discrete primeval forest, revealed a unique and invaluable fungal mycelium biodiversity. Hosting more than one species capable of degrading MNPs, this primeval forest stands as a unique asset toward our capacity to effectively curb MNP pollutants while equally highlighting the importance of preserving and expanding primeval forests surrounding urban and suburban areas within Canada and partnering global regions. Concise actions to mitigate the deleterious impacts of plastic pollution as an amicrobial silent pandemia are presented.

Keywords: Plastics, micro and nanoplastics (MNPs), meso and macroplastics, inflammation, reactive oxygen species (ROS), interleukin 17 (IL17), polyethylene terephthalate (PET), polystyrene (PS), polyethylene (PE), polyvinyl chloride (PVC), polypropylene (PP), low-density polyethylene (LDPE), high-density polyethylene (HDPE), polyhydroxyalkanoates (PHA), polylactic acid (PLA), nNE active biogenic clones, proteasomes, biocorona, fungi mycelium, microbiome, meconium, functional polyethylene terephthalate-degrading enzymes (PETases), primeval forest, opsonins, SLC5A12 lactate transporter, TLR4 / NOX2 axis, CD4+T cells, inflammation, GPR81, PET46 (RLI42440.1) feruloyl esterase, cytochrome P450 1A1 (CYP1A1), electron transport chain (ETC), tumour necrosis factor (TNF), interferon gamma (IFN-γ), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-12 (IL-12) β-amyloid peptides Aβ₄₀ and Aβ₄₂, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), metabolic dysfunction-associated fatty liver disease (MAFLD), C-type lectin receptors L-SIGN / LSECtin, raman microspectroscopic, micro-Fourier Transform Infrared spectroscopy µFTIR/ spectroscopy/microscopy, Economic Co-operation and Development (OECD), Single-use Plastics Prohibition Regulations (SUPPR), Canada's Plastics Science Agenda (CaPSA)

Article

Plastics and Plastic Types

Based on patented records from the mid 1800s, there is the notion that the predecessor of existing plastics was invented in 1856 with subsequent formulation improvements in 1957 by Alexander Parkes, an apprentice at a foundry in Birmingham, England [1]. Although Parkes would proceed to the industrial manufacturing and commercialization of his invention known as parkesine, a semi-synthetic plastic or nitrocellulose, due to its rigidity and labile structure, this product was eventually discontinued. Nonetheless, this first invention led to the formulation and production of a variety of plastics. In 1907, invented by Leo Baekeland, the commercialization and use of Bakelite, one of the oldest polymers, was used in a variety of products including kitchen counters and laboratory benches to musical instruments [2]. This was followed by the production of polyvinyl chloride (PVC) in 1912 [3] with the majority of plastic products currently in use being manufactured from 1913-1974.

In reference to Pareto Securities [4], there exists seven types of plastics which account for nearly 80% of European/global consumption, these are as follows:

Due to their level of plasticity, polypropylene (PP) and polyethylene types have been mostly used in packaging, while PVC, a more durable and resistant material, has been used in construction and manufacturing. Though the use of PVC continues to grow, it has been extensively categorised as one of the most dangerous plastic types - particularly known for its toxicity through degradation and carcinogenic effects [3]. PVC, containing the highest abundance of additives, poses the greatest risk with its degradation, in addition to its chloride composition, releasing toxic chlorine gas as it degrades. It has equally been found that PVC may contain unpolymerized toxic monomers of vinyl chloride known for their role in the onset of various cancer types in humans, particularly of liver angiosarcomas [5]. Nonetheless, from an industrial standpoint, the addition of additives predominantly plasticizers, not only increase PVC flexibility but significantly avert or hinder microbial-dependent accelerated degradation [3,5]. As such, additives in plastic play a major role in determining the span of its degradation. Coupled to its toxicity, additives are namely added to polymer precursors to induce polymerization and ultimately the creation of plastics some of which, as mentioned earlier, are also employed to enhance their physical properties or durability [6]. Under current untenable industrial processes leading to ubiquitous, long-lasting pollution and harm to humans, wildlife and the environment, the exclusion of additives would render plastics far less functional for daily use, calling for the need to use bioprocesses and biomaterials far less polluting and harmful. To better assess and understand the use of plastic additives on route to develop better and more performant materials voided of toxicity and a threat to wildlife, humans and the environment currently used plastic additives can be classified according to their function (Table 1).

Table 1. Classifications along with sub classifications of plastic additives. Typical concentration percentages are those reported by Hansen et al. [8].

Regardless of additives being covalently bound to the polymers constituting plastic itself, during their process of degradation, they are eventually released into the environment and oceans [6-8, 51,56]. This process is accelerated as larger plastics are degraded into micro and nano plastics (MNPs) [11]. Thus, degradation of additives in association with plastic sizes are key factors in determining the hazardous nature of plastics as they reach the core of insoluble plastic components.

In addition to the most prevalent plastic types previously cited, technological advances in polymer science have enabled, over the course of recent years, the development of newer plastics whose properties may offer interesting advantages in distinct application fields. For instance, biodegradable polymers, particularly those derived from renewable sources, undergo biodegradation and therefore present themselves as more environmentally friendly alternatives to the use of conventional polymers that are derived from fossil fuels [12]. One common example of such polymers are polyhydroxyalkanoates (PHAs), which may be produced, among other methods, via microbial fermentation. In the medical industry, PHAs have been widely used in applications like tissue engineering, protein purification, and vaccine delivery due to their biodegradability, biocompatibility, and tunable properties [13-15]. Other emerging plastic types are advanced polymer composites (APCs), which are hybrid materials that use fibers (e.g., carbon, glass) or micro/nanoparticles to reinforce a polymer matrix, thereby allowing the obtention of properties that neither of the two materials alone could provide [16-17]. Such attributes include, but are not limited to, enhanced mechanical strength and thermal stability as well as higher strength-to-weight ratios. In industries like the automotive and aerospace ones, the attributes provided by APCs become particularly useful due to their potential use in applications that may involve high temperatures, exert high mechanical loads, and simultaneously require fuel economy and improved performance [18-20].

Plastic Sizes

Plastics can be further classified by size, within three main types [21]:

1. Nanoplastics (0.001-1µm)
2. Microplastics (1µm-5mm)
3. Macroplastics (>25mm)

In view that there are no current internationally standardized set of values regarding plastic size resulting from the degradation of plastic pollutants, two additional subsets have been proposed [22,52]:

1. Mesoplastics (5-25mm)
2. Megaplastics (>50cm)

The classification of plastics plays a crucial role in defining potentials risk or dangers, in particular, as plastic size decreases, there is an increase in danger to humans, animals and the environment alike. Although relatively large and visible to the naked eye, macroplastics can degrade into smaller micro and nanoplastics unseen to the naked eye, thus posing a risk in harmful absorption to the human body, plants, wildlife and all living forms of life surrounding plastic polluted environments [22]. Details of known health risks and illnesses associated with a sustained exposure to plastic pollutants are outlined and discussed in separate Sections. For the sake of simplicity throughout these Sections, the term Micro & Nano Plastics MNPs will continue to be used to collectively denotate the different types of plastics based on their size as indicated above.

Microplastic Degradation

Macroplastic weathering, also referred to as polymer degradation, is a process through which both the chemical and physical structure of polymer chains are altered, causing the plastic to undergo changes in its properties (e.g., loss of mechanical strength, discoloration) and, finally, to fragmentation [23-24]. Plastic weathering is primarily the result of physical, chemical, and biological processes. Physical degradation may be induced by mechanical stress if plastics are subjected to stress that exceeds their ultimate tensile strength. On the other hand, carbon chains in the polymer may be broken due to exposure to sunlight. Such is the case with the chemical process known as ultraviolet (UV) photooxidation; as the plastics absorb energy from UV light, chemical bonds within the plastic begin to break, thereby forming free radicals. The latter can then react with atmospheric oxygen to form peroxy radicals, which will, in turn, react with other polymer molecules to form more free radicals and continue the degradation process [25-26]. Lastly, plastic polymers undergoing biodegradation are broken down into smaller fragments by microorganisms (e.g., fungi, bacteria, and algae). This process typically involves four stages:

1. Biodeterioration
2. Depolymerization
3. Assimilation and
4. Mineralization.

At first, microbes attach themselves to the surface of plastics, creating a biofilm around it collectively identified as plastisphere. Subsequently, interactions between microbes and abiotic factors (e.g., moisture, temperature, pH) cause microorganisms to secrete intra- and extracellular enzymes as well as free radicals. In turn, these cleave polymer chains, thereby turning them into shorter chains or smaller molecules (e.g., oligomers, dimers, and monomers). Once absorbed by microbes, these molecules are mineralized into CO₂ and H₂O, and other inorganic compounds [27-28].

Sources of Micro and Nanoplastics (MNPs) and Their Effect on Ecosystems

Depending upon their source, micro and nanoplastics (MNPs) can be classified as primary or secondary, with primary MNPs being intentionally manufactured as such and secondary MNPs being derived from macroplastic degradation [29]. Examples of primary MNPs include microbeads found in cosmetic and personal care products (e.g., cleansers), while tire wear and water bottles are some amongst several current sources of secondary MNPs [30]. Due to their small size and inherent properties (e.g., stability), MNPs may persist, accumulate, and migrate for extended periods of time in soil, water, and air, thereby having detrimental effects on the environment and health. In relation to the environment, MNPs have the potential to negatively impact soil quality and the growth of plants and microorganisms, preventing them from thriving. Through infiltration, MNPs cause changes in soil physiochemical properties such as soil structure and nutrient content. In fact, accumulation of MNPs may block soil pores, thereby reducing the soil's infiltration rate [31-32]. With pores being blocked, there is increased runoff and a higher potential for soil erosion, besides decreased soil aeration. Factors like lower moisture and oxygen availability then have the effect of slowing down organic matter decomposition, creating a lower release of primary nutrients (i.e., nitrogen, phosphorus, potassium). Moreover, pore blockage decreases the amount of water that can infiltrate the soil, depleting water available for uptake by plant roots. Furthermore, MNPs may enter the body of animals and humans alike through distinct routes, with the main ones being inhalation and ingestion (Figure 1). When MNPs enter the body after breathing contaminated air or intaking contaminated food or water, they first interact with the respiratory and gastrointestinal systems [33]. Subsequently, these particles have the potential to translocate to secondary systems and begin accumulating in tissues and organs (e.g., liver, spleen, kidneys), inducing toxic effects [29]. In animals, different effects and responses to exposure to MNPs have been well documented [33, 34]. Some of these responses range from observed oxidative stress in adult earthworms (Eisenia foetida) having ingested fluorescent MNPs (100nm, 1-100µm) [34] to goldfish (Carassius auratus) having impaired olfactory neural signal transduction after undergoing a 28-day exposure to MNPs (500nm and 30µm) [35]. The extent at which MNPs impact global health and the environment, depends upon both individual bioaccumulation of exposed organisms and biomagnification as MNPs enter and move throughout the food web. In fact, the longer the lifespan of any living species, the more it is consumed - cumulatively - not only in energy, but also in toxins and pollutants, creating a source of concern as the two latter are not easily eliminated and therefore tend to be retained. Additionally, toxin concentrations increase in the food chain with higher trophic levels, which leads to tertiary consumers being the most affected by sequential contaminant accumulation. In reference to humans, MNPs have been shown to cause different health hazards like cardiovascular disease, carcinogenicity, and potential neurotoxicity (see Sections below) [36-38].

Figure 1. Main routes of MNPs contamination in humans and affected organ systems. The respiratory and digestive systems are the first ones affected by MNPs, followed by secondary systems like the nervous, cardiovascular, lymphatic, and urinary systems [39-44].

Recyclable and Non-recyclable Plastics

In addition to their composition and size, plastics can be sub-categorized into recyclables and non-recyclables. Disposing of plastic waste can depend on its biodegradability, related to the constitution of its polymers and additives alike. Generally, plastics can be separated into recyclables and non-recyclables based on their thermodynamic properties, either being classified as thermoplastics or thermosetting plastics. With the former of thermoplastics being plastics that can be subjected to heating and remoulding or cooling without changing their chemical properties, and the latter of thermosetting plastics being able to withstand higher temperatures that cannot be remolded once heated [45]. Thermoplastics are typically all recyclable with exceptions such as PVC mostly being unacceptable for recycling, while thermosetting plastics are considered non-recyclables since they are unable to be used as raw materials to convert into new products. Some examples of thermoplastics include polyethylene (PE), polyvinylchloride (PVC) and polypropylene (PP), whereas examples of thermosetting plastics include epoxy, phenolic, urea-formaldehyde and unsaturated polyesters [45]. Together with the thermodynamics of plastics, composite materials plus additives - as previously discussed, can also play a contributing factor as to what is considered recyclable and non-recyclable. In regard to composite materials, containing a mixture of multiple entities with differing physical or chemical properties, it has proven to be difficult to recycle thermosetting plastics containing composite materials due to complications in separating homogenous components, ultimately limiting recycling activities [45]. Examples of additives with the largest issues of recycling are summarized in Table 2.

Table 2. Classification and examples of additives posing health risks and a reduced recyclability of plastics [9].

In addition to the additives described in Table 2, plastics containing substances under the putative name of 'legacy additives' add to the identification of non-recyclables. These legacy additives are substances that are currently banned or that are strictly regulated as a result of the risks they pose to humans and/or to the environment [9]. Any plastics found to contain even trace amounts of legacy additives risk contamination of other plastics in their vicinity and thus must be considered as non-recyclable along with any of its contaminants. Examples of legacy additives in specific additive classifications typically fall under the examples listed in Table 2, as such, some include phthalate plasticizers such as DEHP, BBP, DBP or DIBP; brominated compound flame retardants such as HBCD, PBDEs, TetraBDE and PentaBDE [9]. To briefly summarize, recyclables and non-recylables can be determined by thermodynamic properties of the polymers, the specific additives comprised within the plastics, and lastly, by the presence of legacy additives.

Despite many types of plastics being recyclable, there is only a relatively small proportion of them that are recycled. In a report released in 2024 by the Organisation for Economic Co-operation and Development (OECD), a baseline scenario - based on current policy conditions regarding worldwide plastic flows - shows that, in 2020, there were an estimated 360 million tonnes (Mt) of generated plastic waste [46]. The distribution of this amount of waste is shown in Figure 2.

Figure 2. Distribution of the 360 Mt of estimated plastic waste generated in 2020 according to the OECD 2024 report's baseline scenario. Most of the waste (245 Mt) was incinerated - with or without energy recovery - or landfilled, whereas 22.5% (81 Mt) was inadequately disposed of and only less than 9.5% (34 Mt) was recycled. Values were extracted from OECD (2024) [46].

The values depicted in Figure 2 shed light onto the limitations of global recycling efforts taking place as of to date [46]. Besides the challenges presented by plastics that are deemed as non-recyclable, several geopolitical, technical and/or financial constraints persist. A persistent restraint encompasses the costs associated to recycling. It appears to be a reduced incentive to recycle used plastics when processing and manufacturing virgin polymers can be more inexpensive and/or energetically more efficient [47-48]. Moreover, there are also considerable issues regarding insufficient or inadequate infrastructure to ensure effective recycling of plastic waste. This may notably be the case in developing nations, where there can be a lack of financial investments and technical capabilities to put in place and maintain solid waste treatment systems [49]. Due to the negative impacts plastic waste may have, as previously mentioned, it becomes critical to put in place concrete and efficient measures that aim to greatly reduce the amount of plastic that is released into ecosystems. One example of such measures is Canada's Single-use Plastics Prohibition Regulations (SUPPR), whose goal is to achieve zero plastic waste by 2030 by banning the manufacture, import and sale of six distinct categories of single-use plastics (i.e., checkout bags, cutlery, foodservice ware, ring carriers, stir sicks, straws) [50].

Ubiquitous Presence of Plastics: A Human Health Burden

Under the broader term of plastics, nano (0.001-1µm), micro (1µm-5mm), meso (5mm-25mm), and macroplastics (>25mm) have been found from the deepest sediments in the oceans to the Earth's stratosphere, particularly in the form of micro/nanoplastic pollutants (MNPs) in the latter case [51-54]. Not being properly assessed for decades, macro/meso plastics and MNPs have surged as a major health burden to all living species including humans. Although the relative abundance and absolute concentrations of MNPs at any given time in different environments continues to be more accurately measured, MNPs cycles between all water bodies, oceans and soils and the atmospheric air we breathe as well as within the humidity, rain and snowfall that surround us. Over the last decade, the presence of MNPs in all forms of terrestrial and marine wildlife has been associated with increasing number of deaths caused by sustained inflammatory processes and blockage of the digestive system, oxidative stress, neurotoxicity and widespread contamination of food webs among other [51,55]. Depending on the nature of the chemical polymer and surrounding environment, the half-life of MNPs could range between 400-1400 years [56,57]. The abundance, widespread distribution and resistance to degradation of MNPs represents a major global health concern.

MNPs in Human Brain

Quantitative, semi-quantitative and qualitative analyses performed in decedent tissue samples obtained from the frontal cortex of the brain using a combination of pyrolysis gas chromatography-mass spectrometry, attenuated total reflectance-Fourier transform infrared spectroscopy and electron microscopy with energy-dispersive spectroscopy, unveiled the presence of MNPs in the brain of deceased individuals [58]. Although various types of micro/nano plastics were present, the most common polymer found consisted primarily of polyethylene nanoscale shard-like fragments regardless of age, sex, race/ethnicity or cause of death [58]. Remarkably, the relative amounts found in the frontal cortex of subjects deceased in 2024 was higher by comparison to those who died in 2016 [58]. Furthermore, patients harnessing an even greater accumulation of MNPs within the frontal cortex suffered from dementia whereby a prominent accumulation of MNPs was observed in cerebrovascular walls and immune cells [58]. There is mounting evidence that MNPs can breach the encephalic or blood-brain barrier (BBB) acting as potential triggers of cognitive-related ailments and neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD) [59-61]. In 2016, at the beginning of the brain tissue sampling and analysis of MNPs, the global plastic production reached 335 million metric tonnes leading to an estimated 242 million tonnes of plastic waste equivalent to 72% of the amount produced in 2016 [62,63]. Interestingly, in 2024 although the global production of plastic increased to 460 million metric tonnes, the estimated plastic waste was set at 220 million metric tonnes equivalent to 48% of the amount produced and hence 24% less waste than that generated in 2016 [62-63]. This implies that although a direct correlation between higher global manufacturing output and less plastic waste in 2024 by comparison to 2016 cannot symmetrically account for the higher amount of MNPs found in the brain frontal cortex in 2024 tissue sampling and analysis by comparison to those found in 2016, the sustained ubiquitous exposure to plastic pollutants represents a tangible health hazard in the onset of neurological disorders. Apart from a global concerted effort to eliminate plastics and most importantly MNPs pollutants, it is vital to underpin the metabolic and cellular routing of MNPs conducive to neurotoxicity and neurodegenerative disorders. To this end, using polystyrene nanoparticles (PSNs) at a concentration of 100 pM, a significantly accelerate nucleation rate of two β-amyloid peptides, namely Aβ₄₀ and Aβ₄₂ subtypes, was observed [59]. This resulted in an increased formation of Aβ oligomers and augmented neurotoxicity in human neuroblastoma SHSY-5Y cells used as a human modelling system of Alzheimer's disease [59]. Primary cell cultures obtained from decedent tissue samples obtained from the frontal cortex of the brain could be an invaluable tool to further assess the potential direct metabolic impairment induced by exposure to MNPs recently found in excessed concentrations across the North Atlantic [56].

From Brain and Blood to Vital Organs: Presence of MNPs in Lungs, Liver, Kidneys, and Placenta

Through a tandem double shot pyrolysis - gas chromatography/mass spectrometry quantitative analytical assays, the measurement of plastic particles ≥700 nm in human whole blood from 22 otherwise healthy individuals was first performed in 2022 [64]. The finding of four prevalent polymers which included polyethylene terephthalate, polyethylene, polymers of styrene and of methyl methacrylate with a mean of the sum quantifiable concentration of plastic particles in blood of 1.6 μg/ml [64], provided the first quantitative demonstration of MNPs' bioavailability in the human body. Possessing the capacity to breach the encephalic or blood-brain barrier (BBB), travelling through the bloodstream, MNPs have been found in several key and temporary organs such as the lungs, liver, kidneys and the human placenta [65-68]. Due to their broad occurrence and concentrations in water, soil, air, and across the food chain, the lungs, liver, kidneys and placenta - all critical to the maintenance of human health - are emerging as reservoirs of MNPs, affecting their function and leading to the onset of various ailments [65-68]. Several routes of human exposure to MNPs encompass among others:

• Inhalation of airborne particles particularly within urban, suburban and industrialized environments
• Ingestion of contaminated water and food
• Transdermal absorption through injured skin may also take place

Having gained entry into the human body, their transient relative distribution would depend upon the main point of entry being able to reach surrounding tissues and organs including the brain. Due to their key roles in human health, in addition to the impact of MNPs in brain functionality and potential incidence of neurodegenerative diseases described in the previous Section, the presence and impact of MNPs in lungs, liver, kidneys and human placenta is separately addressed in the Sections below.

Detection of MNPs in the Lungs

Directly exposed to airborne MNPs, the lungs are particularly susceptible to the increasing accumulation of micro and nanoplastics. The lungs, as the primary interface with atmospheric air, are especially vulnerable to airborne micro and nanoplastics. Recent studies have detected MNPs in bronchoalveolar lavage fluid and lung tissue samples from both occupationally exposed and general populations. Using micro-Fourier Transform Infrared spectroscopy μFTIR/ spectroscopy/microscopy on tissue samples from 11 patients that underwent thoracic surgical procedures either to remove cancerous tissue or to reduce lung volume showed the presence of MNPs [66]. Although on average the amount of MNPs was reported to be 1.42 ± 1.50 MP/g of tissue (expressed as 0.69±0.84 MP/g after background subtraction adjustments), the relative abundance and diversity of MNPs composition depended upon the anatomical sections from where the lung tissue samples were obtained. Intriguingly, the lower region accounted for the highest levels of MNPs detected (Table 3). Nonetheless, the greatest variety of MNPs was found in the upper region of the lung with the lesser amount and variety of MNPs located within the Lingular anatomical region. The most abundant MNPs encompassed:

1. Polypropylene (23%)
2. Polyethylene terephthalate (18%)
3. Resin (15%)

Table 3. Amounts and Anatomical Location of Different MNPs Types in the Lungs.

Quantitative tissue sample analysis performed on 11 patients revealed a greater variety of MNPs in the upper region of the lungs. Nonetheless, this region contained a lesser amount of MNPs by comparison to that found in the lower region being the Lingular part of the lung the least affected [66]. The most abundant MNP types were polypropylene (23%), polyethylene terephthalate (18%) and resin (15%) [66]. Remarkably, samples obtained from female participants contained lower MNP amounts by comparison to those analysed from male individuals whereby some female samples did not show presence of MNPs [66].

Taken together, these results provide clear evidence that in addition to circulating blood, direct exposure to MNPs can take place through inhalation both indoors and outdoors. The fact that a higher level of MNPS was found in the inferior or lower region of the lung could be associated to blood carrying MNPs as blood flow in this region is the highest due to hydrostatic pressure gradient created by the weight of the blood itself and the action of gravity [69]. Although the sample size was relatively small, presence of MNPs was also found to be higher in men (2.09 ± 1.54 MP/g) than in women (0.36 ± 0.50 MP/g) with some female samples showing no detectable levels of MNPs [66]. Further confirmation of gender differences as well as possible different metabolic routing of MNPs in addition to the fact that females possess smaller airways than males [70] could lead to the identification and development of active biomolecules capable of reducing or eliminating MNPs within upper airways and the lungs. This is of paramount importance. Due to the ubiquitous presence of MNPs within indoor and outdoor environments, it has been estimated that daily inhalation of MNPs ranges between 6-272 MNPs with an approximate annual average rate of 2.16 x 10³ MNPs [71] and upper mean value of 50.74 x 10³ MNPs. This fairly high level of ambient exposure to MNPs implies that a highly efficient mechanism of filtration and elimination of MNPs in the upper respiratory tract could reduce access to the lungs. Although nasal mucus can partially entrapped MNPs, the penetration of MNPs deep into the respiratory tract and ultimately into the lungs appears to be dependent upon respiratory rates and geometrical shapes of MNPs. Briefly, slow breathing rates appear to favour the accumulation of MNPs within critical regions such as the nasal cavity, laryngopharynx, and larynx whereby non-spherical MNPs have a tendency to attain deeper lung penetration leading to different health outcomes affecting the respiratory tract and lungs potentially promoting the onset of a variety of disorders in otherwise healthy individuals [72,73]. These include pulmonary fibrosis, pulmonary frosted glass nodules, asthma and potentially lung cancer in non-smokers or otherwise healthy individuals [73,74]. The sustained indoor and outdoor exposure to a variety of MNP polymers and to the chemical additives they contain underlines the immediate and decisive need to tackle an ever growing and ubiquitous plastic and MNPs pollution already being harnessed within vital organs such as the lungs.

Cellular and Metabolic Triggers of Lung Exposure to MNPs

At a cellular level, in vitro studies using human lung epithelial cells (bronchial epithelium transformed with Ad12-SV40 2B, BEAS-2B) and (human pulmonary alveolar epithelial cells, HPAEpiC) it was recently found that exposure to increasing amounts of polystyrene nanoplastics (PS-NPs) ranging from 7.5 to 30 μg/cm² lead to significant alterations of selective genes in a dose-dependent fashion [75]. Briefly, microarray assays showed dose-dependent gene alteration patterns with 770 genes affected at concentrations of 7.5 μg/cm² and 1951 genes at an exposure of 30 μg/cm² respectively when compared to the control set of unexposed cells [75]. In addition to the aforementioned gene alterations, based upon the assessment of cytosolic reactive oxygen species (ROS), superoxide anion and oxidoreductase activity, it was proposed that exposure to PS-NPs induces a redox imbalance most likely playing a pivotal role in inducing lung injury [75]. The quantitative assessment of a redox disruption induced by PS-NPs, calls for a closer look at critical intracellular pathways surrounding both the intracellular glutathione-glutathione reductase system as well as that of the extracellular thioredoxin-thioredoxin reductase system in individuals with circulating MNPs levels ≥ 1.6 μg/ml. Based upon the differential accumulation of MNPs in the lungs at distinct breathing rates [72,73] as well as the apparent role of MNPs on gut microbiome dysbiosis [76], it is of interest to compare the effect of nNE active biogenic clone gut microbiota [77] on the reversal of microbiome dysbiosis in a population suffering from obesity and exercise deficit disorder with slow breathing rates and circulating MNPs levels ≥ 1.6 μg/ml.

In closing, long-term exposure to MNPs not solely appears to trigger a redox imbalance inducing lung injury, inflammation and apoptotic-dependent cell death, they equally seem to decrease transepithelial electrical resistance through the reduction of tight junctional proteins which together with an increase in matrix metalloproteinase 9 and Surfactant protein A they could reduce the ability of lung cells to repair causing lung tissue impairment and ultimately lung cancer [74-76].

Detection of MNPs in Human Liver

The sustained exposure to MNPs by means of breathing air, drinking water and by their presence within all levels of the food web, facilitates a direct entry of MNPs into the respiratory and digestive systems respectively (see Figure 1). In addition, MNPs could also reach the circulatory system through their potential direct transdermal passage into the blood stream. As described in the previous Section, asymmetrically deposited in the lungs, MNPs can equally reach the blood stream from the lungs. After gaining access to the digestion system through ingestion, MNPs can also be translocated into the blood stream. The translocation of MNPs from the digestive system into the bloodstream can take place through the following processes:

1. Transcellular Endocytosis
2. Paracellular Transport
3. Microfold M-Cell Mediated Uptake

During transcellular endocytosis, MNPs are engulfed by a variety of cells, eventually entering the blood stream [78]. By comparison, a direct passage of MNPs into the blood stream takes place by means of paracellular transport in which alterations of tight junctions enable their passage between cells [79]. As an integral component of the gut's immune system, acting as gatekeepers in the follicle-associated epithelium of Peyer's patches, microfold cells can facilitate the systemic transport of MNPs through lymphoid tissues [80].

The sustained exogenous exposure to MNPs together with the blood-mediated systemic transport and potential exchange of MNPs among tissues and organs increases the probability of harmful accumulation of MNPs in main organs such as the liver (Figure 3).

Figure 3. The sustained exogenous exposure to MNPs (black arrows) together with the blood-mediated systemic transport and potential exchange of MNPs among tissues and organs (red arrows) increases the probability of harmful accumulation of MNPs in main organs such as the liver.

Chemical digests from liver tissue samples analysed after Nile red staining with fluorescent microscopy and Raman spectroscopy revealed the presence of six different microplastic polymers ranging from 4 to 30 μm in size [81]. These polymers included:

1. Polystyrene (PS)
2. Polyvinyl chloride (PVC)
3. Polyethylene terephthalate (PET)
4. Polymethyl methacrylate (PMMA)
5. Polyoxymethylene (POM)
6. Polypropylene (PP)

Presence of these polymers were detected in liver samples from individuals afflicted by cirrhosis with undetectable levels in otherwise healthy liver tissue with no clinical signs of liver disease [81]. Hence, it is of relevance to further evaluate if liver accumulation of MNPs is a driver of liver injury and the onset of fibrosis or it is the result of increased pressure within the portal venous system, carrying blood from the digestive organs to the liver which is known to be elevated in patients suffering from cirrhosis. In this regard, more recent studies have shown that presence of MNPs in the liver could lead to oxidative stress [82,83]. Briefly, MNPs can induce the production of extracellular reactive oxygen species (ROS) in view of their resistance to heat and light degradation [82]. Intracellularly, MNPs appear to be capable of generating ROS by affecting the membrane potential and integrity of the mitochondria and hence the mitochondrial enzymic complexes I and III of the electron transport chain (ETC), essential for the synthesis of ATP [83]. The sustained driven insult of MNPs on cell redox can subsequently lead to a variety of deleterious processes such as genotoxicity, DNA damage, lipid peroxidation, alterations in protein thiolation state and misfolding among other [65,82,83]. It has been proposed that these series of concurrent changes could be at the centre of MNPs-associated liver diseases such as metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease and liver cirrhosis [65,81,84].

Liver Cellular & Metabolic Alterations After Chronic Exposure to MNPs

While an early correlation between exposure to unpolymerized toxic monomers of vinyl chloride and the incidence of liver diseases such as liver angiosarcomas was first reported in 1985 [5], it is only recently that cellular and metabolic changes in the liver due to sustained exposure to MNPs have been elucidated. Chronic exogenous and blood-mediated systemic liver exposure to MNPs can lead to focal accumulation of MNPs triggering inflammation, fibrosis and consequential metabolic changes observed during liver cirrhosis and portal hypertension [65,81]. Key cellular alterations induced by MNPs in the liver encompass both mobilization of immune cells in response to inflammation as well as intracellular changes affecting vital pathways. Accumulation of MNPs in the liver leads to the activation of liver sinusoidal epithelial cells (LSECs) which in turn activate both major histocompatibility complex molecules class I (MHC I), prompting cytotoxic T- cells, and major histocompatibility complex molecules class II (MHCII), inducing B- cell activation and immunoglobulin/antibody production through presentation of MNPs-derived antigens in a similar fashion as those induced by other types of nanoparticles [85]. These responses are locally modulated through the expression of two C-type lectin receptors, namely L-SIGN and LSECtin [86,87]. Briefly, in an exquisite localized regulatory pathway, liver sinusoidal epithelial cells (LSECs) can silence T-cell activation by otherwise universal antigen presentation by dendritic cells [88]. This silencing mechanism, crucial in preventing liver damage is achieved through the expression and binding, in a protein-glycan-dependent manner, of LSECtin to T-cell surface molecule CD44 expressed on dendritic cells-activated T cells [88]. It appears that this local silencing pathway takes place if LSECs also had physical contact with T cells apart from that incurred by dendritic cells [88]. As exposure to MNPs becomes a chronic insult, it is highly possible that dendritic-cell activation of T cells becomes more prevalent overriding the localized liver sinusoidal epithelial cells (LSECs)/LSECtin CD44 T-cell attenuated response prompted by MNPs accumulation in the liver. By achieving a sustained activation of MHCI and MHCII, MNPs may provoke an increased exposure to proinflammatory cytokines such as tumour necrosis factor (TNF), interferon gamma ((IFN-γ), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-12 (IL-12) among other, contributing to liver dysfunction and fibrosis [65, 81,88].

From a metabolic perspective, critical changes induced by MNPs within the liver are most likely initiated by the concerted binding of MNPs to circulating biomolecules, among others, to globular proteins, lipids, carbohydrates and nucleic acids. These interactions lead to the dynamic formation of MNPs-biocorona complexes with selective compositions depending upon the physical and chemical composition of MNPs themselves [85]. Briefly, as MNPs enter the blood stream, some bind to globular proteins with high affinity to MNPs by means of both electrostatic and hydrophobic interactions forming an inner hard protein biocorona. As the hard- protein biocorona continues circulating, it forms weaker and more dynamic interactions with other globular polypeptides constituting an outer coating or soft protein biocorona kept together through London dispersion or van der Waals forces (Figure 4).

Figure 4. Binding of MNPs to Circulating Globular Proteins. As MNPs enter the blood stream they get adsorbed by a variety of glycoproteins with different non-covalent avidities such as electrostatic and hydrophobic forces creating a hard protein biocorona. Other polypeptides interact with the hard protein biocorona through dynamic London dispersion or van der Waals forces forming a soft protein corona. Eventually these MNPs protein biocorona complexes gain entry into the liver and other vital organs such as the spleen and lungs causing inflammation and changes in various metabolic pathways.

Amongst the different components of the protein biocorona, prominent opsonins such as immunoglobulins IgG and IgM as well as complement proteins such as C1q, C3b and C4b effectively tag MNPs prompting their rapid clearance from circulation though phagocytic uptake by the reticuloendothelial system and, in due course, their clearance in liver, spleen or lungs [85]. MNPs gathered within the liver have been associated with alterations in both the synthesis and catabolic pathways of lipids prompting hepatic steatosis and the eventual onset of non-alcoholic fatty liver disease (NAFLD) [89]. Interestingly, analysis of the entire set of RNA molecules or transcriptome suggests that exposure to MNPs may disrupt the peroxisome proliferator-activated receptors (PPAR) signalling pathway encompassing the isoforms PPARα, PPARγ and PPARδ [89]. In particular, MNPs appears to impair PPARγ signalling pathway leading to hepatic lipid accumulation contributing to NAFLD development [89]. These metabolic alterations together with epidemiological data collected from the National Health and Nutrition Examination Survey (NHANES/2013-2016 cycles), targeting daily plastic bottled water intake also revealed a significant positive correlation between bottled water consumption and hepatic steatosis index (HIS) further inferring the role of MNPs in the onset of non-alcoholic fatty liver disease (NAFLD) [89]. The latter underscores the potential public health significance of the intake of MNPs from bottled water raising awareness about the need to curve this trend. In addition to water bottles other single-use plastic containers such as those used in takeaway food containers, namely made from polyamide (PA), polyurethane (PU) and polystyrene (PS), could also lead to a substantial exposure to MNPs. Using focal plane array (FPA)-based micro-FT-IR imaging, it has been estimated that persons ordering take away food 5 to 10 times per month are likely to ingest between 145 to 5520 MNPs from the aforesaid food containers [90].

Micro and nanoplastics (MNPs) may also disrupt glucose homeostasis by affecting glucose metabolic pathways and insulin signalling leading to metabolic impairments such as insulin resistance [91]. Based on animal models, it has been proposed that MNPs may disrupt glucose metabolism by interfering with the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway [92]. Briefly, an increased phosphorylation of insulin receptor substrate-1 appears to cause a decrease of Akt in the PI3K/Akt pathway, which in turn results in insulin resistance and increased plasma glucose in the liver [92]. These observations call for a robust clinical and experimental assessment of the potential correlation between circulating blood levels of MNPs, the onset of insulin resistance and the risk of developing type 2 diabetes in humans.

Additional metabolic pathways altered by the presence of MNPs in the liver encompass the activity and expression of cytochrome P450 isoenzymes (CYPS) impeding their activity and capacity to eliminate endotoxins and xenobiotics including pharmaceuticals, pesticides and dietary pollutants among other [93]. Recent studies using computational molecular docking and modelling, revealed that MNPs of polystyrene (PS), polymethyl methacrylate (PMMA), polyvinyl chloride (PVC), polyethylene (PE), polyurethane (PU), polyethylene terephthalate (PET), polychloroprene (PCP), and polycarbonate (PC) can directly bind to Cytochrome P450 1A1 (CYP1A1) isoenzyme with various binding affinities (Table 4) [94]. Interestingly, these measurements revealed that PC, PET and PS posses the highest binding affinity towards CYP1A1 whereby polycarbonate (PC) is most likely to adversely modulate its biological activity and potentially induce cytotoxicity.

Table 4. Estimated Binding Affinities of various MNPs to Human Cytochrome P450 1A1 (CYP1A1). Molecular docking in silico analysis was used to estimate the potential binding of polystyrene (PS), polymethyl methacrylate (PMMA), polyvinyl chloride (PVC), polyethylene (PE), polyurethane (PU), polyethylene terephthalate (PET), polychloroprene (PCP), and polycarbonate (PC) to human Cytochrome P450 1A1 (CYP1A1) isoenzyme. PC, PET and PS displayed the highest binding affinity to human CYP1A1 reflecting their potential to induce a decrease capacity of this isoenzyme to eliminate endotoxins and xenobiotics including pharmaceuticals, pesticides and dietary pollutants [93].

Liver dysfunctions prompted by the presence of MNPs may also involve disruptions in the synthesis and catalysis of amino acids triggering alterations in protein turnover and overall liver functionality [95]. Involved in the removal and proteolysis of ubiquitin-tagged damaged, unfolded or redundant proteins to sustain cellular homeostasis, MNPs appear to also disrupt the thermodynamic stability and aggregation dynamics of proteasomes [96]. Apart from in vivo animal studies, ex vivo exposure of E. coli cell lysates and human blood plasma to polystyrene (PS) MNPs significantly increased heat-induced endpoint turbidity of proteasome/(PS) MNPs mixtures as well as negative/lower thermodynamic stability ΔTm values [96]. It is of paramount relevance to directly analyse the impact of circulating MNPs biocoronas on proteasomes as they play pivotal roles in DNA repair, cell cycle regulation and immune responses through peptide antigen presentation in addition to ensuring functional signalling pathways by discarding dysfunctional polypeptides among other vital cellular functions [96-97].

Detection of MNPs in Human Kidneys

Recent advances in microRaman spectroscopy have facilitated the detection of MNPs in various human fluids and tissues including urine and kidneys [67]. These studies have revealed the presence of MNPs in human urine and kidneys with different dimensions ranging from 3 to 13 μm in urine and from 1 to 29 μm in kidneys respectively [67]. The most common MNPs found were polyethylene (PE) and polystyrene (PS) both of which can bind and disrupt the activity of Cytochrome P450 1A1 (CYP1A1) isoenzyme present in the kidney of which polystyrene (PS) present in this organ is particularly concerning due to is relatively high binding affinity towards Cytochrome P450 1A1 (CYP1A1) isoenzyme (Table 4) [67,93]. The potential disruption of P450 1A1 (CYP1A1) by PS could preclude its role in the metabolism of a variety of endogenous compounds including hormones and waste products like urea, and exogenous compounds (xenobiotics) like drugs and toxins [98]. Contrariwise, it remains important to determine the potential ancillary induction of CYP1A1 by MNPs present in the kidney enhancing the CYP1A1-mediated conversion of procarcinogens and kidney disease.

Cellular and Metabolic Changes in Human Kidneys Induced by MNPs

Exposure of human-thee-dimensional miniature kidney tissues engineered from patient-derived induced pluripotent stem cells (iPSCs) to polystyrene PS-MNPs have been associated with disturbances in nephrogenesis as well as with renal toxicity [99]. Briefly, exposure of iPSCs organoids at sequential developmental stages including nephron progenitor cell (NPC), renal vesicle, and comma-shaped body to PS-MNPs (1 μm), hampered otherwise normal nephrogenesis as monitored on unexposed iPSCs organoids [99]. This was reflected by a reduction in organoids size, abnormal tubular pattering of nephrons and an overall aberrant nephron structure [99]. Interestingly, the negative impact of PS-MNPs on nephrogenesis was observed both, during short term or sustained exposure whereby PS-MNPs appeared to be bound to the surface of cells during nephron progenitor cell (NPC) stage, accumulating thereafter within glomerulus-like structures of the exposed kidney organoids. Comparable to the effect of MNPs in other tissues and organs, at the cellular level, exposure to PS-MNPs led to an increase of reactive oxygen species (ROS) production inducing apoptosis of NPCs during early stages of development [99]. Moreover, transcriptomic analysis of iPSCs performed at nephron progenitor cell NPC phase and endpoint stages showed a downregulation of transmembrane notch receptors NOTCH 1-4 known to be involved in several developmental and cell type specification which explains the reduction in cell viability and smaller size of iPSCs organoids exposed to PS-MNPs [99]. This constitutes a relevant contribution to enact sentinel programmes aimed at detecting blood levels of MNPs in pregnant women based on the recent detection of MNPs in human placental tissue samples [68] which may compromise normal fetal development. Based on the potential role of Leucine Aminopeptidase (LAP) as an accessory receptor for the immediate viral entry of HIV viral particles and inflammation [100] and similar binding patterns of MNPs to the cell surface membrane, it is of interest to determine the expression and activity of LAP at the nephron progenitor cell (NPC) stage, time at which, binding of PS-MNPs to iPSC first takes place. This could provide additional tools to better understand and evaluate the impact of our current level of exposure to MNPs. There are a number of metabolic changes in the kidney resulting from MNPs exposure. Structural and functional changes impinged by MNPs in the kidneys can alter electrolyte and acid-base homeostasis namely driven by an impairment in the electrolyte gradient of bicarbonate, sodium and potassium caused by MNPs-driven cumulative damage of the kidneys [101]. Apart from endogenous factors influencing the stability and survival of kidney cells, exogenous toxins such as MNPs can rapidly accumulate in the kidneys due to their complexity and high blood flow rates [102]. On average, the kidneys filter around 195 litres of blood daily [103] which translates into approximately 8.1 litres of blood being filtered by the kidneys every hour whereby on average, total blood crosses through the kidneys about 1.6 times during this time period. This considerable amount of blood circulating through the kidneys leads to a greater proportion of MNPs being accumulated in the urinary system by comparison to that accumulated in other organs such as the intestines, heart, and liver regardless of their primary route of entry [104]. As a result, MNPs entering and accumulating in the kidneys and urinary system lead to reactive oxygen species (ROS) production inducing apoptosis, inflammation and clearing auto phagocytic processes altering kidney metabolic pathways and ultimately kidney tissue fibrosis [104]. From a broader metabolic perspective, MNPs-induced damage on kidney cells also affects mitochondrial functionality leading to a decreased generation of ATP, disturbances in lipid and protein synthesis and catabolism as well as alterations in the activities of enzymes such as superoxide dismutase and glutathione peroxidase which are essential in detoxification and antioxidant protection [104-106] (Figure 5).

Figure 5. Sustained accumulation of MNPs in kidneys and urinary system. As blood flows into the kidneys, approximately 195 litres of blood are filtered daily at an average rate of 8.1 litres per hour. Exposure to MNPs from various sources, ultimately accumulate in the kidneys leading to MNPs-induced kidney cells damage and fibrosis. Eventually, this leads to decreased mitochondrial ATP synthesis, disturbances in lipid and protein synthesis and catabolism as well as modifications in selective enzyme activities such as superoxide dismutase and glutathione peroxidase pivotal in detoxification and antioxidant protection.

Detection of MNPs in Human Placenta

Nearly four years ago, tissue samples obtained from 6 placentas obtained after vaginal deliveries from otherwise healthy women were collected by consent from volunteer participants [68]. Four tissue samples from the maternal side, five located within the fetal side and three within the chorioamniotic membranes were digested with 10% KOH for seven days at room temperature and filtrates analysed by Raman microspectroscopy to assess the possible presence of MNPs [68]. In 67% of the tissue analysed or 4 out of 6 placentas tested showed distinct patterns and presence of MNPs (Table 5) [68].

Table 5. Distribution, amounts, and general characteristics of MNPs found in human placentas. Tissue samples isolated from 4 out of a total of 6 human placentas (67%) revealed the presence of MNPs after Raman microspectroscopic analysis of tissue digests. On average MNPs ranged in size from 5 to 10 μm with a relative greater concentration located on the fetal side. The main chemical composition of MNPs found was polypropylene (PP).

Although the presence of MNPs in 67% of the placentas analysed is concerning, additional findings are of greater importance. The amounts of MNPS found, 12 in total, were detected in no more than 4% of the total size of the placenta whereby approximately 23 grams out of an average total weight of 600g of an entire placenta was used during each tissue digest and analysis. Hence, it is highly possible that the overall amount of MNPs present in this transient organ is considerably greater. Non biodegradable pigments such as copper phthalocyanine were also found in addition to other pigments such as iron hydroxide oxide and Ultramarine Blue underlining the need to further assess the presence and progressive accumulation of pigmented MNPs in both maternal and embryonic vital tissues and organs. We are currently interested in advancing the analytical and parametric analysis of MNPs in feto-maternal embryonic chimeric stem cells and their possible impact on the immediate and long-term health of newborn babies and their mothers. This bidirectional transplacental cell trafficking or fetal-maternal microchimerism between mother and fetus leads to the presence and persistence of fetal cells in maternal tissues and vice versa decades after birth influencing their health status, onset of potential pathophysiological processes and disease [107]. To the best of our knowledge, the analysis, and quantitative assessment of MNPs in feto-maternal embryonic chimeric stem cells remains largely unexplored. Recent studies, however, have confirmed the presence of MNPs in human placenta, fetal chord blood and more extensively in meconium revealing the high level of deleterious and generational metabolic impact of global MNPs and plastic pollution at large [108]. The types and proportionate amounts of MNPs were found to be asymmetrically distributed amongst placental, fetal chord blood and meconium samples analysed (Figure 6).

Figure 6. Asymmetric distribution of MNPs present in placenta, fetal chord blood and meconium. In all samples analysed, the amount of MNPs present in meconium (80) was higher than those present in placenta (34) and fetal chord blood (14). The meconium showed the higher diversity of MNPs found (14) by comparison to those found in placenta (9) and fetal chord blood (4) respectively. The most common MNPs found in placenta was microplastic cellulose (CEL), poly butene isotactic (PB) in fetal chord blood and polyethylene (PE) in meconium.

Briefly, the higher amounts of MNPs were by large found in the meconium (80) followed by placenta (34) and fetal chord blood (14) [108]. Interestingly, the higher diversity of MNPs found was detected in the meconium (14) followed by those found in placenta (9) and fetal chord blood (4) respectively [108]. Finally, the most common MNPs found in placenta was microplastic cellulose (CEL), poly butene isotactic (PB) in fetal chord blood and polyethylene (PE) in meconium [108]. These results are consistent with previous findings regarding an asymmetric presence and relative abundance of MNPs in human placenta whereby the highest amounts of MNPs were detected on the fetal side of the placenta [68]. Taken together, there are several underlining health concerns related to the presence of MNPs in placenta, fetal chord blood and meconium. The first relates to the sustained accumulation of MNPs in the human placenta with a transitional presence in the fetal chord blood ending in the progressive accumulation within the developing fetus and ultimately the newborn baby as reflected by the higher amounts of MNPs found in the meconium. Secondly, the diversity of MNPs in the meconium by comparison to those found in the placenta and fetal chord blood increases the complexity to properly assess the various metabolic effects of MNPs accumulated during embryogenesis. Finally, although it was possible to differentially identified MNPs found in placenta (microplastic cellulose /CEL), poly butene isotactic (PB) in fetal chord blood and polyethylene (PE) in meconium, the actual original sources of these pollutants and hence exposure of pregnant women to these MNPs remains to be elucidated. Mapping potential geographical and environmental exposure to a diverse source of MNPs through blood sample analysis of newborn babies, children and young adults is crucial to tailor effective preventative health measures to lessen the generational health impact of an otherwise silent "synthetic pandemic" driven by the ubiquitous presence of MNPs.

Deleterious Impact of Plastics and MNPs on Terrestrial and Aquatic Wildlife

As previously outlined in a recent publication, the expansion and protection of urban park-biospheres is pivotal to curve the current and rapid decline of wildlife biodiversity [109]. In addition to the loss of vital land and unique ecosystems such as those surrounding wetlands, relentless erosive anthropogenic activities such as forestry and deforestation, gas and oil production, mining, extensive farming, food production, industrial manufacturing, transportation, and urban growth, have been accompanied by the accumulation of toxic waste and visual plastic pollutants amongst other. Single-use plastic containers commonly utilized for food and beverages, in particular by fast-food restaurants and retailers, are ubiquitously present in green spaces as well as within urban and suburban forest biospheres which host an array of unique indigenous aquatic, terrestrial and bird species. Despite the resiliency of these species, polluting plastic containers and artifacts continue to directly affect their survival due to entanglement and ultimately asphyxiation when plastic objects are not promptly removed from them (Figure 7). Furthermore, ingestion of persistent plastic fragments and debris leads, among other, to internal blockage, bleeding and potentially death by starvation [110-111]. Incidents of this nature have been detected in surrounding green spaces nearby Cardinal Creek and the Ottawa river in eastern Ottawa. Species potentially affected include striped skunks (Mephitis mephitis), wild turkeys (Meleagris gallopavo), blue herons (Ardea Herodias), beavers (Castor canadensis), mallards (Anas platyrhyncos), Canadian geese (Branta canadensis), bald and golden eagles (Haliaeetus leucocephalus, Aquila chrysaetos), red-tailed hawk (Buteo jamaicensis) and Cooper's hawk (Astur cooperii), coyotes (Canis latrans), foxes (Vulpes vulpes), short-tailed weasel (Mustela richardsonii), long-tailed weasel (Neogale frenata), and least weasel (Mustela nivalis), badgers (Taxidea taxus), snapping turtles (Chelydra serpentina) and raccoons (Procyon lotor) among others. These risks have worsened due to an accelerated construction of housing, commercial developments, roads and public light train networks. There is an urgent need to halt the use of single-use plastic containers and cups in public parks and surrounding green spaces and forests. Shorelines and beaches along the Ottawa river as well as creeks such as the Cardinal Creek are in need of an intense cleaning and the articulation of restoration programmes aiming at removing and preventing the constant release of plastic pollutants.

Figure 7. Combined deleterious impact of loss of wetlands ecosystems and ubiquitous plastic pollution on otherwise resilient indigenous wildlife species. In the last two decades, urban and suburban communities in Eastern Ontario, particularly in the Ottawa region, Canada, have experienced a high loss of otherwise green spaces and surrounding forests. Apart from the abrupt reduction of wildlife biodiversity, resilient species are continuously threatened by ingestion of plastic pollutants and suffocation due to entanglement with plastic containers, fishing lines and other plastic artifacts.

It is equally urgent to perform systematic analyses, reporting, and scientific publications concerning the prevalence of plastic contents and packed indigestible materials, found in the digestive tracts of deceased indigenous wildlife species surrounding urban and suburban areas and their impact in the level of fitness and survival of affected species. These types of measures are not solely required across Canada but at a global scale. To date, deceased indigenous wildlife species surrounding urban and suburban spaces are mostly abandoned or collected and disposed of in regular garbage containers. There are several plausible causes of death after the ingestion of plastics by wildlife species. These include:

1. Obstruction of gastrointestinal tract. Indigestible plastic objects can progressively accumulate in various parts of the digestive tract, primarily within the stomach and intestines hindering digestion and absorption of food nutrients.
2. Famine. Ingestion and accumulation of indigestible plastic materials can potentially lead to appetite loss and search for nutritional foods ultimately leading to starvation and death.
3. Internal injuries. As irregular plastic materials are ingested, sharp pieces can cause lacerations, ulceration and/or perforation of organs throughout the entire digestive system causing internal bleeding, chronic inflammation and the onset of infections of vital tissues and organs.
4. Sustained exposure to toxic chemicals. In addition to the toxic nature of a variety of plastic components, toxic chemicals adsorbed within plastic materials could lead to disruption of key metabolic pathways involved in immune responses, increase production of reactive oxygen species (ROS) leading to cellular apoptosis, inflammation, potentially altering the normal function of several vital organs such as the heart, liver, kidneys, pancreas and lungs similar to those induced by MNPs as described in previous Sections.

Most Affected Aquatic and Terrestrial Wildlife

As amply described in previous Sections, plastic and MNPs pollution is relentless and extensive affecting every aquatic, terrestrial and atmospheric compartmental spaces of our planet. As recent international efforts to curve global plastic production remain elusive, it has been estimated that if the current production trend continues, in the next 14 years global plastic production could reach up to 736 metric tonnes [112]. Most of these plastics are found in single-use products increasing the amounts of plastics directly released into the environment [113]. Briefly, roughly 9% of global plastic waste has been successfully recycled, 12% burn up, while the majority (79%) has been exponentially amassed in an array of natural ecosystems [114]. Through various cycles of degradation and redistribution, plastics converted into MNPs are present in all terrestrial soils, oceans, all bodies of water, air and raindrops [115]. As such, all forms of life are constantly exposed to plastics and MNPs pollutants impinging a sustained pressure to the health and survival of all species on Earth including that of humans. Apart from breeding air-suspended MNPs, there is an ever-increasing number of studies signifying that the types and quantities of MNPs present in agricultural soils and aquatic species translate into human health risks through direct ingestion of MNPs-contaminated foods [116-117]. The current and continuous mismanagement of plastic production and global plastic/MNP pollution has driven the onset of a non-biological amicrobial "silent pandemia" with far reaching and enduring global health consequences. Recent studies have undeniably signalled that global plastic life cycle contributes to biodiversity loss and climate change [118-119]. To this end, as of to date, no global concerted and effective strategy has been structured to curve this trend. Plastics and MNPs pose a significant threat to the survival and biodiversity of marine life with all terrestrial species also impacted [120].

Impact of Plastics and MNPs in Aquatic Wildlife

Both fresh water and marine wildlife remain the most affected by the presence of plastics and MNPs, whereby the presence of MNPs and their potential impact on vital functions such as growth and reproduction of producer species at the bottom of the trophic chain is concerning.

Accumulation and Impact of MNPs on Green Microalgae

The extensive and incremental amounts of MNPs accumulating in oceans and terrestrial bodies of water has sparked an interest in determining their effects on primary producers like green microalgae, which play a central role in freshwater and marine food webs. For more than a decade, it has been known that green microalgae such as Chlorella and Scenedesmus species can accumulate MNPs on their external cell surfaces through physical adsorption as well as intracellularly by means of endocytic mechanisms [121-122]. Extracellular and intracellular accumulation of MNPs has proven to hamper microalgal photosynthetic activity [122]. Accumulation of MNPs equally induce the generation of reactive oxygen species (ROS) and hence oxidative stress leading to damage of cell membranes, proteins, and DNA inducing apoptosis [122]. Ultimately, MNPs directly impair aquatic food webs as green microalgal populations get affected [51,122]. In their pivotal role as primary producers, green microalgae are an essential source of food for zooplankton as well as for a variety of small aquatic species [123]. As such, based on their nutritional value, abundance, and accessibility green microalgae represent a keystone for energy transfer within freshwater and marine environments [51,121-123]. Therefore, a sustained imbalance and decline in the health and overall populations of green microalgae may inevitably translate into a reduce food quality and availability affecting the entire food web within freshwater and marine aquatic ecosystems. Furthermore, the bioaccumulation of MNPs in primary producers like green microalgae can lead to an upstream biomagnification of MNPs by their transfer to organisms at higher trophic levels such as fish an ultimately terrestrial species including humans. In addition to the deleterious effects of MNPs in several vital tissues and organs in humans, described in previous Sections, behavioural disorders in fish resulting from MNPs ingestion and biomagnification through the food web have been reported [124]. Such changes appear to be related to the ability of MNPs to effectively penetrate the blood-to-brain barrier leading to brain damage in affected fish [124]. From a broader perspective, the sustained exposure and increasing deleterious amounts of MNPs accumulated on green microalgal populations may also alter oxygen dynamics, nutrient cycling, and overall water quality in affected ecosystems.

Accumulation and Impact of MNPs on Zooplankter Daphnia Magna

Plastics and MNPs have emerged as pervasive global pollutants of aquatic environments. As active filter feeders ingesting water-suspended particles, freshwater zooplankters such as Daphnia magna are particularly susceptible to MNP pollutants. Early experimental studies have shown that exposure to incremental amounts of polystyrene PS-MNPs induce several changes in vital functions of Daphnia magna [121]. These changes include an increase in mortality, severe alterations in body size and reproductive capabilities leading to up to 68% of malformations in neonates [121]. In addition, quantitative ingestion and egestion studies using fluorescent polystyrene micro (2 μm) and nano (100 nm) beads have revealed, among other, a significant reduction in feeding rates (21%) primarily driven by nanobeads [125]. Interestingly, both ingestion and egestion of microbeads (2 μm) were greater than those detected in Daphnia magna fed with nanobeads (100nm) leading to a higher level of hazardous physiological outcomes [125]. To date, consistent adverse effects to Daphnia magna after their exposure to MNPs of various particle sizes have been documented [121,125-126]. These include:

1. Disruption of feeding patterns and digestive impairment impinged by physical obstruction of the digestive system.
2. Reduction in body size and developmental anomalies.
3. Decrease levels of fecundity associated to disturbances during embryogenesis and overall higher mortality rates.
4. Increased production of reactive oxygen species (ROS) and hence oxidative stress.
5. Reduction in swimming fitness and ability to avoid predation leading to disruptions in population dynamics and overall survival.

Fairly recent and elegant proteomic studies have revealed that the relative amounts of 41 proteins out of a total amount of 3784 polypeptides are significantly influenced by the chronic exposure of Daphnia magna to polystyrene PS-MNPs [126]. Briefly, an increment in the amounts of various sulfotransferases as well as in those of gamma-aminobutyric acid transaminase (GABA-T) was detected [126]. This is of interest since these enzymes are involved in several biological functions. Sulfotransferases, for instance, play a pivotal role in the metabolism and excretion of drugs, hormones, and small molecules [127]. GABA-T enzyme, on the other hand, is known to downregulate the levels of the neurotransmitter gamma-aminobutyric acid (GABA) through its involvement in the breakdown of GABA [128]. This process is essential for normal brain function as GABA slows down brain activity [128]. It is hence possible that previously documented changes in behavioural patterns of Daphnia magna after exposure to PS-MNPs [126] is associated to an increase in the amounts of GABA transaminase (GABA-T). In reference to the proteins whose amounts were decreased after PS-MNPs exposure these included the DNA-directed RNA polymerase subunit and additional proteins linked to biotic and inorganic stress and reproduction [126]. This reduction may explain the decrease in fecundity of Daphnia magna after chronic exposure to MNPs [121, 125-126]. Finally, the amounts of several digestive enzyme were also downregulated after exposure to PS-MNPs [126]. These results are also in accordance with disruption of feeding patters and reduced body size detected after exposure of Daphnia magna to MNPs [121, 125-126]. They equally signal that sustained exposure to MNPs, which are commonly found in most environmental samples, may affect the fitness of daphnids. A degradation of the fitness of daphnids could, in turn, harmfully impact freshwater food webs. A decreased survival rate and reproduction could lower Daphnia populations impairing their role as algae grazers and as a prey for upper trophic levels. These encompass several amphibians and fish species ultimately contributing to additional stressors affecting the biodiversity of freshwater ecosystems.

Aquatic and Terrestrial Wildlife Most Affected by Plastics and MNPs

As indicated in previous Sections, the relentless global production of plastic continues to exacerbate the ubiquitous presence of plastics and of MNPs in all aquatic and terrestrial ecosystems. In 2024 the global production of plastic was estimated at 460 million metric tonnes resulting in approximately 220 million metric tonnes of plastic waste [62-63]. Wildlife in all aquatic and terrestrial ecosystems are harmfully impacted through three main consequential venues, namely being physical, physiological/metabolic and behavioural [53,62,80,111,117,120,124] (Figure 8).

Figure 8. Direct impact of plastics and MNPs of terrestrial and aquatic wildlife. Regardless of the individuality of terrestrial and aquatic ecosystems, several wildlife species are equally affected by plastic and MNP pollutants with sustained physical, physiological/metabolic and behavioural consequences.

It is estimated that the basins of the oceans amount to close to 4000 m (3800 m) in depth holding up to 97% of all water on earth [129]. To date, the amount of plastic and MNP pollution is so extensive that plastic and MNP pollutants have covered the deepest ocean floors [130,131]. Annual estimates of plastics entering the oceans attain 8 million tonnes adding to more than 150 million tonnes of plastics already present in all ocean ecosystems [132-133]. The majority of these plastic pollutants (80-90%) are believed to originate from terrestrial sources carried by river currents [132]. Over a decade ago, it was estimated that more than five trillion plastic fragments weighing more than 250,000 tonnes covered the ocean surface [133]. Hence, it is not surprising that 555 species of marine and estuarine fish alone representing 139 families from 31 orders have been affected by the ingestion of plastic fragments and MNP pollutants [134]. However, it is believed that the number of marine species affected ranges between 800 to 2141 with marine mammals such as whales are known to succumb due to entanglement [134-136].

Death of Marine Wildlife Species Caused by Ingestion of Plastics and MNPs

Although a global systematic account and publications of marine wildlife whose deaths were caused by ingestion of plastic debris and MNPs needs to be established, to date, some of these species include:

Cetaceans

1. Atlantic spotted dolphin (Stenella frontalis)
2. Common bottlenose dolphin (Tursiops truncatus)
3. Cuvier's beaked whale (Ziphius cavirostris)
4. Deraniyagala's beaked Whale (Mesoplodon hotaula)
5. Fin whale (Balaenoptera physalus)
6. Gervais' beaked whale (Mesoplodon europaeus)
7. Northern minke whale (Balaenoptera acutorostrata)
8. Pygmy sperm whale (Kogia breviceps)
9. Risso's dolphin (Grampus griseus)
10. Rough-toothed dolphin (Steno bredanensis)
11. Sperm whale (Physeter macrocephalus)
12. Striped dolphin (Stenella coeruleoalba)

Pinnipeds

1. Grey seal (Halichoerus grypus)
2. Harbour seal (Phoca vitulina)

Sea Turtles

1. Flatback sea turtle (Natator depressus)
2. Green sea turtle (Chelonia mydas)
3. Hawksbill sea turtle (Eretmochelys imbricata)
4. Leatherback sea turtle (Dermochelys coriacea)
5. Loggerhead sea turtle (Caretta caretta)

Sea Birds

1. Antarctic prion (Pachyptila desolata)
2. Blue petrel (Halobaena caerulea)
3. Fairy prion (Pachyptila turtur)
4. Great shearwater (Ardenna gravis)
5. Light-mantled sooty albatross (Phoebetria palpebrate)
6. Magellanic penguin (Spheniscus magellanicus)
7. Northern gannet (Morus bassanus)
8. Salvin's prion (Pachyptila salvini)
9. Short-tailed shearwater (Puffinus tenuirostris)

Apart from these vertebrate aquatic marine species, invertebrates such as molluscs, rotifers, echinoderms, polychaetes and cnidarians are also affected by their exposure to and ingestion of MNPs [51,137].

Death of Terrestrial Wildlife Species Caused by Ingestion of Plastics and MNPs

Although most the plastics and MNPs pollutants (80-90%) that gain entry into the marine environments and ecosystems originate from terrestrial contamination of soils and rivers [132], studies on their direct impact on the fitness and survival of terrestrial species are less prominent than those of marine wildlife. Nonetheless, it is known that terrestrial organisms, comprising mammals, birds, insects, amphibians, reptiles and soil-dwelling species, are largely exposed to plastics and MNPs ultimately ingesting these materials with fatal outcomes [138-140]. Some of the species affected encompass:

Mammals

Coyotes (Canis latrans)

Coatis (Nasua nasua)

Crab-eating foxes (Cerdocyon thous)

Maned wolves (Chrysocyon brachyurus)

Hedgehogs (Erinaceidae)

Wood mice (Apodemus sylvaticus)

Bears (Ursidae)

Takin (Budorcas taxicolor)

Leopard cats (Prionailurus bengalensis)

Birds

American Crows (Corvus brachyrhynchos)

Ring-Billed Gulls (Larus delawarensis)

Greater White-Fronted Geese (Anser albifrons)

Great Horned Owls (Bubo virginianus)

Double-crested Cormorants (Phalacrocorax auritus)

Flesh-footed Shearwaters (Ardenna carneipes)

Mute Swans (Cygnus olor)

Trumpeter Swans (Cygnus buccinator)

Mallards (Anas platyrhynchos)

Canada Geese (Branta canadensis)

Reptiles and Amphibians

Snakes (Serpentes): (Trimeresurus kanburiensis), (Ophiophagus hannah)

Tadpoles: American bullfrog (Lithobates catesbeianus)

Northern leopard frog (Lithobates pipiens)

Cane toad (Rhinella marina)

The combined effects of climate change, toxic chemicals released and leached into the oceans in addition to deep and extensive plastic and MNPs pollution, calls for an accelerated and concerted global set of concise and decisive actions to halt the current level of erosion of vital marine ecosystems and loss of wildlife fitness and biodiversity.

From the Human Microbiome to Soil, Fungi Mycelium, and Aquatic Microorganisms: A Promising Set of Bio-tools for MNPs Degradation

Apart from ongoing efforts to physically remove ghost fishing nets and gear, plastic bottles and artifacts as well as meso (5-25mm), macro (>25mm) and megaplastics (>50cm) both in aquatic and terrestrial environments, there is a unique opportunity to explore and identify the emergence of species capable of not solely surviving the current sustained exposure to MNPs but able to brake down these ubiquitous pollutants. There is mounting evidence that aquatic bacteria as well as several microorganisms including those encompassed within the human gut microbiome can break down MNPs [141-143]. Due to their versatility and potential role in reversing the deleterious impact of MNPs in the health of all species affected including that of humans, as amply described in previous Sections, we are particularly interested in the capacity of discrete human microbiome clones as well as in the mycelium of selective fungi to break down MNPs.

Human Gut Microbiome

Fairly recent evaluation of enriched cultures obtained from the feces of six volunteers found that four apparent opportunistic pathogens had the ability to degrade either low-density polyethylene (LDPE) or polypropylene (PP) as determined by a micro-spray method and electron microscopy [141]. However, the precise identification of gut microorganisms, namely bacteria or fungi, capable of deploying selective catalytic enzymes for the efficient degradation of a variety of MNPs, which have been currently found within the digestive system, remains largely unexplored. This is namely due to the complexity and high costs associated with this type of experimental studies [144]. In addition, the presence of MNPs per se may induce dysbiosis altering the dynamics of the gut microbiome, increasing the challenges to successfully identify MNPs-degrading microorganisms [144]. We have found that exogenous sources of the human microbiome have proven to be useful as adjuvant functional foods in individuals suffering from obesity, type 2 diabetes (T2DM) and cancer (see Tables 6A and 6B). Briefly, individuals provided with previously described selective functional foods supplemented with 250 ml culture per os of nNE active biogenic clones once a week [77], for up to 180 days, showed a significant reduction in circulating levels of alkaline phosphatase and lactate dehydrogenase (Tables 6A and 6B). High levels of these blood biomarkers have been associated with poor outcomes of patients suffering from obesity, type 2 diabetes and cancer [145-147]. Amongst the various implications of elevated levels of lactate dehydrogenase, it is known that an increase in lactate production during anaerobic glucose metabolism, activates a signalling molecule involved the modulation of inflammatory responses [148-150]. Briefly, through the SLC5A12 lactate transporter, an increase in lactate could initiate the reprogramming of CD4⁺T cells to enhance inflammation through IL17 or via GPR81, lactate can induce a macrophage-mediated anti-inflammatory state [148-150]. It is hence possible that the reduction of both alkaline phosphatase and lactate dehydrogenase by nNE active biogenic clones might be triggered by interference in the levels of circulating lactate. Remarkably, reduction of both enzymes by nNE active biogenic clones, namely nNE2, nNE4, nNE6, nNE8, nNE10 and nNE11, was equally observed in otherwise healthy individuals. This has sparked an interest in determining detectable blood levels of MNPs in otherwise healthy individuals and the ability of nNE biogenic clones to break down MNPs hence decreasing their presence in blood samples.

Table 6A

Table 6B

Table 6 (A/B). Individuals suffering from obesity, pre-diabetic/type 2 diabetes, cancer as well as otherwise healthy were provided with previously described selective functional foods supplemented with 250 ml culture per os of nNE active biogenic clones once a week for up to 180 days. As part of their routine medical examination circulating levels of alkaline phosphatase (Table 6A) and of lactate dehydrogenase (Table 6B) was recorded on day 1, 90 and 180 days after initial nNE supplementation.

Fungi Mycelium

Amongst some of the species that have been found to degrade various types of plastics and MNP pollutants, the mycelium of certain commonly found fungi such as that of Oyster mushrooms (Pleurotus ostreatus) has been recently found to have the capacity to degrade persistent plastic pollutants such as polyethylene, polystyrene, polyvinyl chloride, and polyethylene terephthalate, breaking them down through the action of secreted enzymes that depolymerize these polymers [143]. It appears that Pleurotus ostreatus mycelium contains and produces laccase, a pivotal enzyme involved in lignin degradation [143]. After cellulose, lignin is the second most abundant complex polymer providing plants with protection from environmental and biological stress while also serving as an anchoring component to bind cellulose fibers together, making it an ideal bio-adhesive polymer [151]. The capacity of Pleurotus ostreatus mycelium to degrade complex and various plastic polymers, through the secretion of laccase has not only conferred this fungus the ability to resist the pervasive presence of plastic and MNP pollutants, but also our ability to articulate efficient bioremediation processes for their decomposition. Interestingly, fungi found to grow on the surface of plastic debris pollutants across the shoreline of Lake Zurich, Switzerland, were also isolated and tested against their ability to degrade polyethylene (PE) and/or polyurethane (PU) [152]. It was found that, amongst the several DNA-identified species of isolated fungi, four distinct species possess the capacity to brake down polyurethane (PU) [152]. These were:

1. Cladosporium cladosporioides
2. Leptosphaeria sp
3. Penicillium griseofulvum
4. Xepiculopsis graminea

This provides additional evidence of the potential role of fungi mycelium found in urban and suburban areas to effectively degrade plastic and MNP pollutants. In search of mycelium from fungi present in otherwise well-preserved ancient forests exposed to urban pollutants, we proceeded to gather valuable historical archives including picture records collected from Reineck Memorial Woods. Void of otherwise invasive species and solely 7.32 acres in size, this discrete primeval forest is part of the homelands of the Bodwéwadmi (Potawatomi), Oma͞eqnomenew-ahkew (Menominee), Očhéthi Šakówiŋ, Hoocąk (Ho-Chunk), and Myaamia people(s) in the State of Wisconsin. Records available expand from 2018 to 2024 (see Table 7 and Figure 9). Analysis of archived data during this time frame revealed various interesting characteristics of fungi mycelium through the detection of an abundance of different mushroom fruiting bodies in this ancient woodland. In total, 203 different fungi species were detected by means of a non-quadrant divided preliminary field census performed within the Reineck Memorial Woods. Although additional and more robust molecular based as well as airborne DNA analysis of fungi spatial and seasonal variability is sought, the number of species found in this old-growth forest revealed an important level of biodiversity considering its rather small size (Table 7 and Figure 9). Furthermore, as depicted in Figure 10, the number of species found per annum showed significant differences in between years with the highest scores detected in 2022 (94) and 2023 (98) respectively.

Table 7. Annual count of observed fungal families/species at Reineck Memorial Woods (7.32 acres) from 2018 to July 2024. In total, 203 different fungi species were detected by means of a non-quadrant divided preliminary field census performed within this ancient woodland. The number of species found within this discrete primeval forest revealed an important level of biodiversity. Most fungi were found on dead or decomposing wood. *Most abundant / frequently encountered species.

Figure 9. Photographic records dating from 2018-2024 of some of the fungi species found in the 7.32 Reineck Memorial Woods old-growth forest.

Figure 10. Annual count of observed fungal families/species at Reineck Memorial Woods old-growth forest (7.32 acres) from 2018 to July 2024. Each bar shows the total number of families/species recorded per year, with the lighter segment representing those identified as most abundant and prevalent in that year.

While several factors are known to facilitate the growth of fungi in primeval forests such as the amount of rainfall leading to consistent optimal moisture, abundant organic matter such as old-growth wood, leaf litter, and other dead organic materials as well as effective nutrient cycling, abundant rainfall and moist environments are crucial for fungal spores to germinate and for fungi mycelia to grow and spread [153]. Records of annual rainfall in the State of Wisconsin, within Division 6 East Central area, where Reineck Memorial Woods primeval forest is located, are summarized on Figure 11 [154]. Although total accumulation levels of rain, and most likely of moisture, were higher in 2018 and 2019 by comparison to those measured in 2022 and 2023, the number of fungal families/species observed in 2018 and 2019 were significantly lower than those found in 2022 and 2023. This unexpected discrepancy could be related to various factors. Apart from possible inconsistencies in the recording methods used during these time periods, other causes include fewer human disturbances due to the onset of COVID-19/SARS CoV-2 pandemic outbreak. Indeed, transitional adaptive plasticity of various species was distinctly witnessed during decreased global human activity and lockdowns undertaken throughout this time frame of the COVID-19/SARS CoV-2 pandemic outbreak [109, 155-158]. More surprisingly, studies addressing climate change-induced draughts and their potential to affect fungal communities and biomass within Swedish boreal forests, a 45-day experimental rainfall exclusion resulted in a similar fungal biomass among areas subjected to rainfall exclusion and control ones exposed to regular rainfall [153]. Nonetheless, the composition of fungal communities was changed [153]. In the case of a real field scenario, fungal species found within the Reineck Memorial Woods primeval forest showed notable changes after lower levels of annual precipitation from 2021 to 2023, particularly in the latter year.

Figure 11. Annual rainfall (2018 to 2024) in the State of Wisconsin within Division 6, East Central area [154]. Reineck Memorial Woods primeval forest lies within this Division.

Although total accumulation levels of rain were higher in 2018 and 2019 by comparison to those measured in 2022 and 2023, the number of fungal families/species observed in 2018 and 2019 were significantly lower than those found in 2022 and 2023 respectively.

Interestingly, from 2022-2023, the number of fungal families/species were not solely higher than those found in years with more abundant levels of precipitation including those reported from 2018 to 2020 but included certain fungal species that were found to be more prevalent/abundant than others (see Figures 10 & 11). Some of these species include the following:

1. Bicoloured Bracket (Gloeoporus dichrous) Golden
2. Scaly Cap (Pholiota aurivella)
3. Honey Mushroom (Armillaria mellea)
4. Mossy Maze Polypore (Cerrena unicolour)
5. Salmon Eggs Slime Mould (Hemitrichia decipiens / Trichia decipiens)
6. Shrimp of the Woods (Entoloma abortivum)
7. Trembling Phlebia (Phlebia tremellosa)

A more detailed analysis of these species revealed that out of the seven prevalent species found between 2022 and 2023, Cerrena unicolor and Phlebia tremellosa have been found to be capable of degrading important plastic precursors such as bisphenol A (BPA) used in the manufacturing of polycarbonate plastics, and derivative pollutants of polycyclic aromatic hydrocarbons (PAHs) [159,160]. The ability of Cerrena unicolor and Phlebia tremellosa to breakdown these compounds is most likely achieved through the production and secretion of ligninolytic enzymes such as laccase, lignin peroxidase and glyoxal oxidase [161]. Although less frequent and abundant Pleurotus ostreatus was also found in 2023 in addition to its finding in previous years, 2019 and 2020 respectively (Table 7). As cited earlier, Pleurotus ostreatus can breakdown ubiquitous plastic pollutants such as polyethylene, polystyrene, polyvinyl chloride, and polyethylene terephthalate [143]. Taken together, the rich fungal biodiversity found in Reineck Memorial Woods primeval forest, with more than one species capable of degrading MNPs, stands as a unique asset towards our capacity to effectively curve MNP pollutants. Briefly, we have a great interest in further determining the presence of MNP pollutants in current and archive soil samples present in this primeval forest and their potential degradation by some of the fungi unveiled in this preliminary assessment. In addition, it is of relevance to explore the possibility of some edible fungal species, such as Pleurotus ostreatus and others, to enhance some of the beneficial properties of nNE active biogenic clones. This encompasses the ability of nNE clones (nNE2, nNE4, nNE6, nNE8, nNE10 and nNE11) to address obesity, type 2 diabetes and cancer as effective adjuvant foods while equally determining their plausible role in the degradation of MNPs within the digestive system.

Aquatic Microorganisms

There is mounting evidence that sustained exposure of marine microorganisms to plastics and MNP pollutants has induced their capacity to degrade MNPs [142]. Recent elegant metagenomic and metatranscriptomic analysis based on computational and artificial intelligence enzymic structure prediction models, it was possible to identify 23 functional polyethylene terephthalate-degrading enzymes (PETases) [142]. Briefly, 332 out of 415 ocean samples revealed 23 PETase variants occurring at depths ranging between 1 and 2 km below the surface as well as across oceans in areas broadly affected by plastic pollutants [142]. Contrary to terrestrial PETases, which are mostly encoded and transcribed by a variety of bacterial organisms, marine PETases were found primarily within species belonging to the order of Pseudomonadales such as Pseudomonas spp without being able to determine their exact composition due to the dynamic nature of the marine ecosystems [142]. In addition to Pseudomonas spp and other species of the order of Pseudomonadales, other bacterial marine species capable of breaking down plastics and MNPs include:

1. Alcanivorax sp. N3-2A isolated from the seaboards of Canada within the North Atlantic Ocean capable of degrading alkanes and polyhydroxybutyrate (PHB) [162].
2. Rhodococcus sp. C-2 able to degrade low-density polyethylene (LDPE). Representing close to 20% of the global plastic production, vast amounts of LDPE are discharged into the oceans deeply affecting various marine species and ecosystems [163].

Under the vast and persistent exposure to plastics with annual estimates of these pollutants entering the oceans at a current rate of 8 million tonnes in addition to more than 150 million tonnes of plastics already present in all ocean ecosystems [132-133], microorganisms, other than bacteria, have also been found to degrade plastics and MNPs due to their persistence and high levels of exposure to these contaminants. Marine fungi such as Aspergillus caespitosus, Aspergillus flavus, Penicillium chrysogenum, Penicillium citrinum, Penicillium griseofulvum among others as well as algae can breakdown plastic polymers [28,164,165]. Some of these plastics include polymers such as polyethylene terephthalate (PET), polystyrene (PS), polyethylene (PE), polyvinyl chloride (PVC), and polypropylene (PP) [28,164,165].

Perhaps the most relevant aquatic microorganisms with the metabolic capacity to degrade plastics and MNPs encompass members of the extremophile halophilic archaea. Adapted to survive and grow in environments with high salt concentrations such as salt marshes, saline lakes, coastal lagoons, and hypersaline regions of the ocean they have been found to equally posses the ability to degrade various types of plastics and MNPs [166-168]. In this regard, the versatility of extremophile halophilic archaea as well as their unique capability to thrive in rather diverse and harsh salty environments, provide a unique opportunity to articulate effective removal of plastic and MNP pollutants. Beyond their capacity to adapt and thrive within salt marshes, saline lakes, coastal lagoons, and hypersaline regions of the ocean, they have been found to degrade, to a various extent, diverse plastics and MNP pollutants [166-168]. Some of the most important of these plastics and MNP pollutants include:

• Polyethylene (PE): Perhaps one of the most broadly used plastics. It is used in packaging, bottles, and bags. Some halophilic archaea have also demonstrated the ability to partially degrade Low-Density Polyethylene (LDPE) as well as High-Density Polyethylene (HDPE). Nonetheless, this process is slow, often requiring pretreatment.
• Polypropylene (PP): Found in containers, automotive parts, and textiles. Certain marine halophilic archaea can initiate oxidative degradation of polypropylene, particularly when combined with environmental factors such as UV radiation and mechanical abrasion.
• Polyvinyl Chloride (PVC): Commonly found in piping, construction, and medical devices. While PVC is generally resistant to biodegradation, some halophilic archaea have shown potential to break down plasticizers and additives within PVC materials.
• Polyester-based plastics such as Polyethylene Terephthalate (PET), Polyhydroxyalkanoate (PHA) and, Polylactic Acid (PLA):
  • Polyethylene terephthalate (PET): Namely used in bottles and textiles, PET is highly resistant to natural degradation. Nonetheless, certain halophilic archaea, particularly those with specialized esterases and lipases, have demonstrated limited degradation of PET surfaces.
  • Polyhydroxyalkanoates (PHA) and Polylactic acid (PLA): These bioplastics are more prone to microbial catalysis whereby marine halophilic archaea can degrade them efficiently, making them preferable for applications where marine biodegradability is sought.

The recent finding, structural and biochemical characterization of PET46 (RLI42440.1) feruloyl esterase isolated from archaeon Candidatus Bathyarchaeota, an archaeal promiscuous feruloyl esterase exhibiting degradation activity on semi-crystalline Polyethylene terephthalate (PET) [166], provides a unique opportunity to articulate viable bioremediation strategies taking advantage of their capacity to tolerate higher temperatures and salinity concentrations.

Conclusions and Next Actions

From early records of patents dated from the mid 1800s, there is the notion that the predecessor of existing plastics was invented in 1856 with subsequent formulation improvements in 1957 by Alexander Parkes, an apprentice at a foundry in Birmingham, England [1]. Since the first appearance of parkesine, a rather rigid and brittle plastic primordial based on the invention of Parkes, commencing in the 1950's, the industrial manufacturing of an array of plastic polymers have relentlessly expanded. Recent estimates consolidated by the Organisation for Economic Co-operation and Development (OECD) within its 2024 report, revealed that 360 Mt of plastic waste was generated in 2020 [46]. The majority of this waste (68%) was incinerated, while 81Mt (22.5) was improperly discharged and merely 34 Mt (9.5%) properly recycled (9.5%) [46]. Apart from the ubiquitous, global presence of plastic waste, nano (0.001-1µm), micro (1µm-5mm), meso (5mm-25mm), and macroplastic (>25mm) pollutants have been found within deep ocean floor sediments as well as at heights reaching the Earth's stratosphere [51-54]. As of 2025, international efforts to halt current rates of global plastic production remain elusive. Consequently, if current plastic manufacturing rates remain unchanged, we could reach up to 736 metric tonnes of plastics being produced within the next 14 years [112,113]. Taking into account that most of the finished plastics are found in single-use products, the amounts of plastics directly released into the environment will continue to grow hence accelerating the global presence of deleterious micro and nano plastic (MNP) pollutants. Over a decade ago, in the oceans alone, it was estimated that more than five trillion plastic fragments, including MNPs, weighing more than 250,000 tonnes spread across their surface [133].To date, estimates of plastics entering the oceans every year attain 8 million tonnes in addition to more than 150 million tonnes of plastics already present in all ocean ecosystems most of which, are believed to originate from terrestrial sources brought to the ocean by river currents [132-133]. By means of degradation and relocation, plastics transformed into MNPs are present in all terrestrial soils, oceans, all bodies of water, air and raindrops [115]. From marine and terrestrial microorganisms, invertebrates such as insects and vertebrates including mammals to plants and fungi, all forms of life are continuously being exposed to plastics and MNPs pollutants altering their health and ultimately the survival of all species on Earth including that of humans. In addition to breeding air-suspended MNPs and transdermal penetration, there is a cumulative number of studies signifying that the types and quantities of MNPs present in soils, water, terrestrial and aquatic species translate into human health risks through direct ingestion of MNPs-contaminated foods and water sources (Figure 3) [116-117]. From a broader perspective, most terrestrial and aquatic food webs have been compromised by the extensive and global presence of plastics and MNP pollutants. These pollutants have directly affected wildlife survival through harmful physical, physiological/metabolic and behavioural alterations in most aquatic and terrestrial ecosystems (Figure 8) [53,62,80,111,117,120,124]. From entanglement and suffocation to slow death caused by obstruction of the digestive tract, the physical impact of plastics on wildlife is palpable in both aquatic and terrestrial ecosystems including those within urban and suburban green spaces and forests (Figure 7). Common physiological and metabolic alterations induced by MNPs include the induction of reactive oxygen species (ROS) shifting the membrane potential and integrity of the mitochondria and ultimately the mitochondrial enzymic complexes I and III of the electron transport chain (ETC), pivotal for the synthesis of ATP [83]. MNPs-induced excess of reactive oxygen species (ROS), primarily superoxide, hydrogen peroxide, hydroxyl radical, singlet oxygen and peroxynitrite is perhaps one of the most concerning. Briefly, the continual insult of MNPs on cell redox systems modulated by glutathione/glutathione reductase and thioredoxin/thioredoxin reductase respectively, can subsequently lead to a variety of deleterious processes. These include, among others, genotoxicity, lipid peroxidation, alterations in protein thiolation state and misfolding [65,82,83]. ROS DNA mediated oxidation, could eventually lead to enduring lesions such as the formation of 8-hydroxyguanine (8-oxo-dG) by attacking DNA bases and sugar, prompting mutations, strand breaks, genome instability, and the onset of a variety of diseases such as cardiovascular disorders, neurodegenerative ailments and cancer [169-172]. Perhaps the most relevant advances to address and to potentially mitigate the deleterious effects of MNPs in human and affected wildlife resides in our capacity to measure these pollutants in blood samples [64]. MNPs detected in 22 otherwise healthy participants using double shot pyrolysis - gas chromatography/mass spectrometry quantitative analytical analyses attained mean levels of 1.6 μg/ml [64]. MNPs detected comprised polyethylene terephthalate, polyethylene, polymers of styrene and of methyl methacrylate, all of which are known to induce an increase in ROS [173]. This technology has recently enabled the identification of polyethylene MNPs in intervertebral disc samples and their potential role in intervertebral disc degeneration via ROS-mediated oxidative stress and activation of the TLR4 / NOX2 axis [173]. This in turn appears to lead to the senescence of nucleus pulposus cells at the centre of the spinal discs [173]. A common physiological/metabolic change prone by a sustained exposure to MNPs is inflammation, which among other factors, it could be triggered by increased ROS-mediated oxidative stress [104,169-172]. In reference to MNPs-induced inflammation, we report, for the first time, that individuals provided with previously described selective functional foods supplemented with 250 ml culture per os of nNE active biogenic clones once a week [77], for up to 180 days, showed a significant reduction in circulating levels of alkaline phosphatase and lactate dehydrogenase (Tables 6A and 6B). Although we have consistently detected a reduction in these enzymes in subjects suffering from obesity, type 2 diabetes and cancer, this is the first time we observed a 25% reduction in alkaline phosphatase and a 23.5% decrease in lactate dehydrogenase levels in otherwise healthy individuals after 180 days supplementation with nNE active biogenic clones provided once a week (Tables 6A and 6B). This significant reduction in both enzymes is of particular relevance due to their role in the dynamics and modulation of inflammation. In the context of cellular injury, like that induced by MNPs and the consequential release of lactate, SLC5A12 lactate transporter leads to the reprogramming of CD4⁺T cells prompting inflammation via IL17 as well as its subsequent attenuation by GPR81 to induce a macrophage-mediated anti-inflammatory state [148-150]. This is equally accompanied by an increase in alkaline phosphatase which functions as a pivotal anti-inflammatory mediator dephosphorylating and inactivating a variety of inflammation-triggering molecules [174]. The significant reduction in both lactate dehydrogenase and alkaline phosphatase by nNE clones (nNE2, nNE4, nNE6, nNE8, nNE10 and nNE11) in both individuals suffering from obesity, type 2 diabetes and cancer as well within otherwise healthy persons, signals their potential role in the attenuation of the aforesaid inflammatory pathways. It is conceivable that this role is attained through modulation of lactate levels as well as by attenuating inflammation induced through dysbiosis commonly experienced in most patients affected by obesity, type 2 diabetes, cancer and, potentially, by the presence of MNPS [175-178]. In addition, the reduction of alkaline phosphatase and lactate dehydrogenase in otherwise healthy individuals sparks the exciting possibility that nNE clones might be directly involved in the degradation of MNPs most likely present in this population. In this context, it is of great interest to measure blood circulating levels of MNPs during the course of diet regiments consisting of selective functional foods supplemented with 250 ml of nNE active biogenic clone cultures per os once a week. This could translate into a relevant contribution towards the abrogation of MNPs pollutants most likely present in the global population. Concerning the degradation of MNPs found in most living species, including humans, as well as within global ecosystems, the role of fungi mycelium and archaea deserve special attention. Species of interest include fungi found in Reineck Memorial Woods. These encompass:

1. Bicoloured Bracket (Gloeoporus dichrous) Golden
2. Scaly Cap (Pholiota aurivella)
3. Honey Mushroom (Armillaria mellea)
4. Mossy Maze Polypore (Cerrena unicolour)
5. Salmon Eggs Slime Mould (Hemitrichia decipiens / Trichia decipiens)
6. Shrimp of the Woods (Entoloma abortivum)
7. Trembling Phlebia (Phlebia tremellosa)
8. Oyster Mushroom (Pleurotus ostreatus)

Out of these species, Cerrena unicolour, Phlebia tremellosa and Pleurotus ostreatus are known to degrade plastics and MNP pollutants through the production and secretion of ligninolytic enzymes such as laccase, lignin peroxidase and glyoxal oxidase [143,159-161]. Beyond the potential role of fungi mycelium in the degradation of plastic and MNP pollutants, the remarkable biodiversity of fungi found within Reineck Memorial Woods discrete primeval forest hosting no less than 203 different species, could be at the basis of articulating a more robust understanding of their potential role in the bioremediation of soils and forests severely affected by plastic and MNP pollution. In this regard, apart from performing more structured field censuses complemented with airborne DNA analysis of fungi spatial and seasonal variability, it is of great importance to analyse archived soils samples from 2018 to 2024 for their potential content of plastic and MNP pollutants. From the sheer perspective of human health, it is of interest to explore the prospect of some edible fungal species, such as Pleurotus ostreatus and others, to enhance some of the beneficial properties of nNE active biogenic clones. This encompasses the ability of nNE clones (nNE2, nNE4, nNE6, nNE8, nNE10 and nNE11) to address obesity, type 2 diabetes and cancer as effective adjuvant foods while equally determining their plausible role in the degradation of MNPs within the digestive system. Concerning the role of aquatic microorganisms with the metabolic make up to catabolise plastics and MNPs, species belonging to extremophile halophilic archaea deserve a special attention. Capable to thrive in rather harsh environments, immersed in high salt concentrations, such as salt marshes, saline lakes, coastal lagoons, and hypersaline regions of the sea they appear to equally posses the ability to catabolise various types of plastics and MNPs [166-168]. The archaeon Candidatus Bathyarchaeota has emerged as a promising microorganism to design movable in-line bioreactors for the adsorption and degradation of MNPs. This could be achieved based on the recent discovery, structural and biochemical characterization of PET46 (RLI42440.1) feruloyl esterase isolated from Candidatus Bathyarchaeota [166]. This archaeal promiscuous feruloyl esterase exhibiting catalytic properties against Polyethylene terephthalate (PET), offers a remarkable prospect to articulate viable bioremediation strategies taking advantage of the capacity of Candidatus Bathyarchaeota to tolerate higher temperatures and salinity concentrations.

Next Actions

From the primordial of plastics emerging as early as 1856 to the full industrial manufacturing of the most currently used plastics such as polyvinyl chloride (PVC) in 1926, low-density polyethylene (LDPE) in 1939, high-density polyethylene (HDPE) in 1955 and polypropylene (PP) in 1957 [1-4], the estimated global production of plastics in 2024 attained 460 million metric tonnes, generating 220 million metric tonnes of plastic waste [62-63]. Merely 9% (19.8 Mt) was recycled [179]. This trend hasn't been limited to 2024 with substantial, global amounts of plastics and MNPs being accumulated since the industrial production of plastics in 1926. As such, plastics, nano (0.001-1µm), micro (1µm-5mm), meso (5mm-25mm), and macroplastics (>25mm) are known to be present within the deepest sediments of the sea as well as in the form of micro/nanoplastic pollutants (MNPs) dispersed across the Earth's stratosphere [51-54]. Extensively described in previous Sections, in addition to humans, all forms of life have been severely affected by plastic and MNP pollutants throughout global ecosystems and food webs present in all latitudes and climatic zones. Apart from their detection in vital organs of the digestive, respiratory, nervous, cardiovascular, lymphatic and urinary systems (Figure 1), their presence in temporary organs such as the human placenta, has signalled a generational transfer of MNPs to the fetus during the entire human embryogenesis as revealed by their finding in fetal/newborn meconium (Figure 6). The generational transfer of MNP pollutants is not exclusive to humans but most likely a pathologic phenomenon intersecting all living organisms on our planet Earth. This magnitude of pollution has been impinged by the relentless manufacturing of plastics, the inadequate management of single-use plastics, a poor containment and recycling of plastics in their entirety. Over the last decades, we have unveiled and witnessed the emergence of a man-made, amicrobial "Silent Pandemia" affecting the health, fitness and survival of a palpable number of species including that of humans.

In closing, with the current level of contempt and/or inability of some medium to high-income regions and countries to enact concise actions to address plastic and MNP pollutants, and their deleterious impact on One/Planetary Health, Canada should enact concise programmes and actions across all provinces, territories and global regions with common interests. These should include:

• Set an annual quota in the amount of newly manufactured plastics, primarily of polyvinyl chloride (PVC), low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP), polystyrene (PS) and polycarbonate (PC) requiring 75-100% content of recycled materials in all products containing these plastic types including laboratory, medical devices and equipment.
• Accelerate biomass microbial fermentation for the industrial manufacturing and use of emerging bioplastics such as polyhydroxyalkanoate (PHA) as well as that of grapevine-derived plastics.
• In addition to achieving the effective ban of single-use plastics, restrict the use of plastics of any type including those currently used in cups, containers and wrapping materials in all public parks, urban and suburban forests, rivers, lakes and seashores. A ban on open circular plastic covers, capable of strangling wildlife, must be implemented prior to the completion of the domestic action plan aiming to achieve zero plastic waste by 2030.
• Accelerate the design of less pollutant and life-threatening fishing gear and the retrieval of lost (ghost) fishing gear from all water bodies to be achieved prior to 2030.
• Perform routine analyses on soil, air and water samples to determine the amounts, distribution and types of plastic and MNP pollutants present in forests and ecosystems surrounding urban and suburban areas.
• Based upon the analyses and presence of plastic and MNP pollutants in forests and ecosystems surrounding urban and suburban areas, prioritise their physical removal and biodegradation.
• Accelerate the industrial manufacturing of fish gills-inspired semi-crossflow filtration systems to remove MNPs at source and from drinking water [180].
• Develop movable Candidatus Bathyarchaeota containing in-line bioreactors for the adsorption and degradation of MNPs present in rivers, lakes and seashores. This could be achieved in tandem with floating plastic and MNP capturing devices powered by solar energy and water currents.
• As part of the routine testing panels currently in used across Canada for disease prevention and diagnosis, include the measurement of MNPs present in circulating blood samples, umbilical cord, aliquots of placental tissue and meconium.
• Halt the direct disposal of dead birds and of all wild animals and perform a systematic analysis of the presence of plastics and MNPs in blood and digestive tract.
• Perform a detailed mapping and censuses of all indigenous species present in primeval forests in Canada. In the case of primeval forests present close to urban and suburban areas ensure the creation and protection of 40 - 50 km² Indigenous-Wildlife-Urban Park Biospheres (IWUPBs) within major cities across Canada [109].
• Expand current role in the removal of plastic and MNP pollutants from the Great Pacific Garbage Patch brough to Vancouver Island for processing.

Leading in these pressing priorities and technological innovations, Canada will not only mitigate the current imbalances created by volatile geopolitical pressures but will also create a resourceful strategy with global health benefits, financial retributions, and employment. Under the current mandated reduction of all federal departments, Canada's Plastics Science Agenda (CaPSA) should not only remain intact but better funded and known by the scientific community and the Canadian population at large.

Acknowledgments

Illustrations: Figure 1 was partly generated using Servier Medical Art.

Accessed July 26, 2025, by Laura Camila Peñuela Cárdenas, provided by Servier (https://smart.servier.com/) and licensed under a Creative Commons Attribution 4.0 unported licence (https://creativecommons.org/licenses/by/4.0/)

For reprints, please use the contact form, below, or address the corresponding author, listed above.

© 2026 JEHSI, https://doi.org/10.21964/jehsi-00009

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