Lithuanian University of Health Sciences Faculty of Medicine

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Lithuanian University of Health Sciences Faculty of Medicine

Department of Environmental Medicine Paula Pilar Navarro Gascón

Title of Final Master’s Thesis:

Micro-plastics, Nano-plastics and it’s components on the impact of human health

Kaunas 2019-2020

Thesis supervisor: Prof. Dalia Lukšienė

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TABLE OF CONTENTS

1. SUMMARY……….. 3

2. ACKNOWLEDGMENTS ……….. 4

3. CONFLITC OF INTEREST ……….. 4

4. ETHICS COMMITTEE APPROVAL ………. 4

5. ABBREVIATION LIST ………. 5

6. TERMS ……… 6

7. INTRODUCTION ……….. 7

8. AIMS AND OBJECTIVES 8.1 Aims ……… 8

8.2 Objectives ………... 8

9. METHODOLOGY ………..8

10. POLLUTANTS IN THE ENVIRONMENT 10.1 Creation ………. 9

10.1.1. Pollutants in our environment ………. 14

10.1.2. Interaction with other elements ………... 18

10.1.2.1. Bioaccumulation and bio-amplification ………. 18

10.1.2.2. Absorption of heavy metals and pharmaceuticals ……… 20

10.1.2.3 Bacteria, virus and algae ……… 21

10.3 The effects on animals ………... 24

10.3.1. Direct impact on animals ………. 24

10.3.2. Impact in the trophic chain ……….. 28

10.4 The effects on human health ………. 30

10.4.1. Human exposure ………..30

10.4.2 Impact of MP and NP in human health ……….... 32

10.4.2.1 Microbiota in the gastrointestinal tract ………. 33

10.4.2.2 Central nervous system ………. 35

10.4.2.3 The skin ……….... 35

10.4.2.4 The placenta ………. 36

10.4.2.5 The immune system ……….. 37

10.4.3.6 The lungs ……….. 38

10.4.3. Impact of the additives in human health ………. 40

10.4.3.1 Phthalates ……… 40

10.4.3.2 Bisphenol A ………... 41

11. DISCUSSION OF THE RESULTS ………. 44

11.1 Strength and Limitations ……… 46

12. CONCLUSIONS ………47

13. REFERENCE ……… 48

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1. SUMMARY

Author: Paula Pilar Navarro Gascon

Research title: Micro-plastics, Nano-plastics and it’s components on the impact of human health.

Aim: To analyze recent scientific literature on Micro and Nano-plastics and its components and how those impact or could affect the health and well-being of humans in short and long-time exposure.

Objectives:

1. To analyze scientific literature on micro, nano-plastics and understand how plastic get in contact with our environment (the manufacture and recycling or disposal of plastics; the plastics

interactions with bacteria, virus, protozoa and fungi.)

2. To analyze scientific literature on micro, nano-plastics and understand how pollutants of plastics enter the water, food chain and how do they act with animals and plants.

3. To analyze scientific literature on micro, nano-plastics and understand how they act on human health (the impact of derivates of plastics on human health, emphasize the role in the

gastrointestinal, reproductive, immunological, endocrinological, and central nervous system). Methodology: This is a Literature review where searches were conducted using some of the most popular medical literature databases such a: PubMed, UpToDate and Cochrane. The literature chosen covers the last 10 years and all the articles hves been assessed in ist entirety. The terms used were: 'Microplastics pollution' 'Nanoplastics pollution' 'Effects of Nanoplastics in health' 'Effects of Microplastics in humans' 'Micro and Nanoplastics risk for human health' 'Creation of Micro and Nanoplastics' 'Risk Microplastics' 'Effects of Nanoplastics in the environment' 'Airborne Micro and Nanoplastics'. Keywords were matched to database indexing terms.

Results and conclusions:

There are enough pieces of evidences that support the idea that micro and nanoplastics are chronic pollutants in the human environment. Nevertheless, the few studies that relate microplastics and nanoplastics with human health, are limited, however they draw a clear correlation between these new pollutants in our environment, and harmful effects in our immunological, endocrinological, reproductive, respiratory and cardiac systems. Further research should be put in place to study and investigated the real

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2. ACKNOWLEDGMENTS

To my family, the constant support in my live, that has given me so much, asking for so little in return. Lastly, I would like to extend my thanks to my supervisor Prof. Dalia Lukšienė for her advice thought this

literature review project.

3. CONFLICT OF INTERESTS

The author has declared that no competing interests exist.

4. ETHICS COMMITTEEP APROVAL

Due to the methodology of the Master Thesis a Literature Review, is not indicated to issue an ethics committee approval.

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5. ABBREVIATION LIST

MP Microplastics TCS Triclosan

MaP Macroplastics SCFAs Short chain fatty acids NM Nanoplastics HAB Harmful alga bloom POP Persistent Organic Pollutant. ATB Antibiotics

BPA Bisphenol A UTI Urinary tract infections

GPGP Great Pacific Garbage Patch ARG Antibiotic resistance genes MB Microbead Mt Metric tones PE Polyethylene PP Polypropylene PS Polystyrene PVC Polyvinyl chloride

PET Polyethylene terephthalate EDC Endocrine disruptor chemical PHT Phthalates

ESC Environmental stress cracking WWTP Water waste treatment plant WHO World health organization HM Heavy metals

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6. TERMS

- Bisphenol A, used as the precursor for polycarbonates and epoxy and vinyl esters resins, has been recently shown to be associated with various types of CV diseases when present in high concentrations in urine, according to epidemiological studies [18]. Bisphenol A is suspected of being endocrine disrupting chemicals.

- Phthalates are industrial chemicals that have been used for a variety of purposes. They are included into children's toys and medical devices to make them softer and more flexible. They are found in the chemical composition of paints, pharmaceuticals, food products and personal care products. Phthalates are suspected of being endocrine disrupting chemicals [17].

- Polymers are any of a class of natural or synthetic substances, composed of macromolecules, that are multiples of simpler chemical units called monomers. In this thesis the term polymers would be describing: microplastics, nanoplastics and macroplastics.

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7. INTRODUCTION

In 1869, John Wesley Hyatt created the first natural cellulose's polymer, this was the first attempt of many from the scientifly community to create these new materials that soon would revolutionize the world that we live in [1][2]. However, this is not until the middle of the 20th century during the second great world (1939-1945) when these new materials are exploited and mass produced for military use, and once the conflict is over, exported for the use of our daily lives [3][4].

Plastics are long chain polymer molecules that are made out of raw material like petroleum, coal and natural gas. In order to make these new materials more resistant in time, during the manufacture several additives are included to satisfy all these necessities, such as; stabilizers (it will suppress de degradation), fillers (improves the performance), plasticizers (decrease viscosity), colorants (to achieve the color) [5]. Plastics can be created in different sizes such as: macroplastics (MaP) particles bigger than 5mm in size, microplastics (MP) are particles smaller than 5mm in size, and nanoplastics (NP) are particles smaller than 1 μm or less than 100 nm in size [6].

Since the moment that plastics leave the manufacture, they are exposed to the elements of the environment (mechanical, chemical and physical forces) and it accidentally started to breakdown into smaller fragments of itself. In 1979 global production of plastic was 62 million of tons, in 1999 this number increased up to 160 million of tons in 2014 this figure has risep to 311 millins tons, this statistic indicated that the production of plastics in exponentially increasing through time [7].

The useful lifetime of the objects made out of plastics could vary from few seconds to years depending on their composition and design, nonetheless the lifespans that these objects have as debris are completely different. Plastic waste is being disposed in recycling plants (9%), used to recover energy (12%), discarded in a landfill (8%), or lost in the environment (71%) [8].

So plastic debris are present in the environment in a way that it has been suggested as a geological indicator for the Anthropocene area [3]. During the years different studies had proven that microplastics and Nanoplastics have been alternating the health of up to 655 species of animals [9].

Plastics had disturbed and infiltrated the food chain, being in some of our basic food and beverages as water, salt, fish, seafood [10]. Microplastics and nanoplastics had proven to deteriorate the immune, metabolic and gastrointestinal systems of many animals [11].

The objective of this master thesis is to describe the pathways in which microplastics and nanoplastics become pollutants in our environment and their interactions ie human health. Focusing on the immunological, metabolic and endocrinological systems he human health.

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8. AIMS AND OBJECTIVES

8.1 AIMS

Aim: To analyze recent scientific literature on Micro and Nanoplastics and its components and how those impact or could affect the health and well-being of humans in short and long-time exposure.

8.2 OBJECTIVES

Objectives:

1. To analyze scientific literature on micro, nanoplastics and understand how plastic get in contact with our environment (the manufacture and recycling or disposal of plastics; the plastics

interactions with bacteria, virus, protozoa and fungi).

2. To analyze scientific literature on micro, nanoplastics and understand how pollutants of plastics enten the water, food chain and how do they act with animals and plants.

3. To analyze scientific literature on micro, nanoplastics and understand how they act on human health (the impact of derivates of plastics on human health, emphasize the role in the gastrointestinal, reproductive, immunological, endocrinological, and central nervous system).

9. METHODOLOGY

The study of microplastics and nanoplastics as pollutants, started in the 1970's were the first

experiments where conducted, withal in the past decade it has become and emergent and prominent topic of study. The searches were conducted using some of the most popular medical literature

databases such s: PubMed, UpToDate and Cochrane. The literature chosen covers the last 10 years and all the articles veas been assessed in sit entirety. The terms used were: 'Microplastics pollution'

'Nanoplastics pollution' 'Effects of Nanoplastics in health' 'Effects of Microplastics in humans' 'Micro and Nano plastics risk for human health' 'Creation of Micro and Nanoplastics' 'Risk Microplastics' 'Effects of Nano plastics in the environment' 'Airborne Micro and Nanoplastics’. Keywords were matched to database indexing terms, 230 were the original articles and review obtained in the first search. A screening was carried out using the title of the study and the abstract. After, a thorough selection 78 references have been user to execute this Final Master Thesis.

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10. POLLUTANTS IN THE ENVIRONMENT

10.1 CREATION:

In 1997, the Capitan Charles Moore sailed to the North Pacific Gyre between the subtropical waters of California and Hawaii. Day after day of the journey the sailors could not believe what they were seeing, there were no fishes or dolphins. All they could see were objects made out of plastics. Years later it has been estimated that at least 79 (45-129) thousands of tons of plastic debris are floating inside of this area of 1,6 million km2, a figure sixteen times higher than previously reported. Therefore, this was named the Great Pacific Garbage Patch (GPGP) [12].

Subsequently after researching on the topic, the number of plastics in the ocean was not as shocking as the nature of the problem: Microscopic.

During the manufacturing of plastics different shapes, compositions and sizes could take place to fulfill the necessities of the product. When we talk about microplastic (MP) it is important to make a clear destination between primary plastics and secondary plastics.

The primary plastics or also called virgin polymers, are those which are manufacture in the size desired. 8300 million metric tons (Mt) of virgin plastic had been produced up until 2015, out of tem 50% are for single used purposes [3]. In the industry field, there is production of macro-plastics (MaP) (>5mm) e.g a bottle of water, along with the production of MP (<5mm) manufactures mostly for the cosmetic business, or so called microbead (MB) [6]. Secondary plastics are those that through the different exposition to the elements and time they have been deteriorated and collapsed into smaller particles originating from primary plastics. These could be MaP being fractured into smaller particles or MP that tear into much more petite particles.

MP and nanoplastics (NP) are present in our daily lives. The biggest sources of these particles are: Synthetic textiles, tires, city dust, road making products, marine coats, personal care products, plastic pellets, 3D printers, medical equipment and products of transportations [13].

Figure 1 presents the categories and sources of MPs in the environment. There are different types of Plastic materials, their composition is defined during manufacture. Their configuration is adapted to their purpose of design. The most common types of plastics in the world are [14][15]:

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• Polyethylene (PE): Low density: Used for bags, plastic wraps. Density form: bottle caps, shampoo and conditioner bottles.

• Polypropylene (PP): Yoghurt packaging, semi-rigid containers, straws, plastic dippers, tupperware. • Polystyrene (PS): Foam food containers, plastic cutlery, disposable coffee cups.

• Polyvinyl chloride (PVC): Toys, pipes, window frames, shoes. • Polyethylene terephthalate (PET): Bottles, food trays, rope, carpets.

• Other miscellaneous plastics (polycarbonate, polalyctide, acrylic, acrylonitrile butadiene, styrene, fiberglass, and nylon): CD’s, DVD’s, medical storage products, glasses, baby bottles.

Plastics are manufactured in different shapes according to their abilities and utility, those are:

The most abundant shape in microplastics are fibers (48,5%), fragments 31 %, beads 6,5%, films 5,5%, and foam 3,5% [3].

Fig 1. Categories and sources of MPs in the environment. (P. Wu, et al.) [13].

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Nevertheless, the plastic itself does not have the ability to either exert extreme flexibility or thermo resistance without disintegrating or to having the desired color for the costumer. To satisfy all these necessities, other chemical components are added to the polymers.

These organic and inorganic materials are presented in Table 1.

Name Used Types

Stabilizers Prolongs the lifetime of the polymer, by suppressing the degradation

1. Antioxidants: Antiozonants, primary antioxidants (Radical Scavengers), secondary antioxidants (Hydroperoxides scavengers).

2. Light stabilizers: UV absorbers, quenchers, bisphenol A, hindered amine light stabilizers.

3. Other: Acid Scavengers, heat Stabilizers, flame retardants, biocides.

Fillers Improves the performance of the material and reduces its cost of production.

E.G: Calcium carbonate, nanofillers…

Plasticizers Improve the rheology of the polymer. Increasing the plasticity and decreasing the viscosity.

1. Dicarboxylic/tricarboxylic ester-based plasticizers: resistance to water and oils is required. E.G: Phthalates 2. Trimellitates: resistance to high temperature is required. E.G: TMTM, ATM…

3. Adipates, sebacates, maleates: resistance to low temperatures and UV light.

4. Other: Azelates, benzolates…

Colorant To achieve the color of the plastic.

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The mentioned chemical products that are described above were not invented to be pollutants. However, the poor waste management that society does on plastic residues is one of the main reasons behind their high pollutant activity. It is estimated that 71% of debris will end up in the environment, 8% in landfills and eventually come in contact with humans as pollutants [8]. A large amount of these additives have small molecular size and are not chemically bound to the polymer, making them more inclined to leach out into the environment. [16].

Even though plastics fulfill their purpose during manufacture, if the conditions of maintenance conditions are not optimal, meticulous or they are exposed to any process that could damage their structure, small particles of the MP and NP with their additives, could start detaching from it, ending in the environment.

It was estimated that 4.8 to12.7 milliof tons of plastic wastes entered the marine environment in 2010 and 100 to 250 million tons are predicted by 2025 [19].

The same properties that make plastics so versatile in innumerable applications durability, and resistance to degradation, make these materials difficult or impossible for nature to degraded them. The only perpetual course in which plastic waste is eliminated is through thermal processes as combustion or pyrolysis in specialize centers with or without recovery of energy. The environmental and health impact of the incinerations depends on their design [3]. If plastics are burned in the open space without any kind of preventive measures, the polymers would release toxic substances that could threat and affect the areas around, including the ecosystem and the health of individuals [5]. E.g.: If PE, PP or PS are exposed to an increase of temperature, carbon monoxide would be released in the process. If PVC is forced under high temperatures, digoxin, black carbon, and arrogates would be the result of the chemical process, all of the chemical components mention above can damage the human health if exposure to them [5].

It is essential to focus on explaining the meaning of compostable bioplastics or plastics so call biodegradable (Fig. 2). These polymers would not degrade in the environment per see, there are parameters corresponding to temperature, oxygen saturation and salinity that should take place in a close environment for these bioplastics to safely being compostable and recycled, otherwise they will start a process of breakdown in the environment as the rest of the non-bioplastics [20].

To understand the breakdown in nature, it is essential to have in account the size, shape, surface, chemical composition and environmental conditions of each polymer. These conditions could be occurring in the

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outdoor environment (sea water, lake, sand…), indoor environment (houses, hospitals, schools…) where the debris are disposed.

The most common process of damage of plastics are chemical, physical and mechanical pathways: Exposure to UV light [8], Photooxidation, and hydrolytic degradation [13], mechanical fracture, environmental stress cracking (ESC): water turbulence & coalitions, bio-assimilation by microorganism, wind erosion [21] and sand abrasion. These different pathways would complement each other to form MP and NP. E.g.: the UV light exposure or the hydrolytic degradation would debilitate the connections between the material making it more fragile and susceptible to sand abrasion, creating in this way more MP and NP. During the process of fragmentation, the ESC would change the properties of the MP and NP making them more susceptible to absorbed persistent organic pollutant that are in the environment [13].

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It is of vital importance to understand that the size of the MP and NP is inversely correlated to their ability to absorb persistent organic pollutant (POP) and positively correlated with damage in human health [22][23]. E.g.: the smaller the MP and NP, the bigger ability would have to adsorb POP.

The ocean acidifications due to the adsorption from the increment quantities of carbon dioxide from the atmosphere, plays a really important role in the abilities of MP and NP to adsorb POP and heavy metals (HM) from the sea. Studies have proven that at lower pH the adsorption abilities are optimal [24].

The process of disintegration would occur in all forms of MP and NP, such as: Microbeads, Nurdles, Fibers, Foams, Fragments. E.g.: Our clothes, furniture, carpets and curtains are no longer made out of cotton or wool, instead our clothes are made out of plastics, fibers such as acrylic, polyamide or polyester, to be more precise. As a result of it, when the fibers get under so much mechanical, chemical or physical stress, microfibers that are already loosely get detached and released in the surrounding environment, as a consequence of laundry, dryer, ironing, UV light [25].

These new microfibers would most likely end up in the water system, Water waste treatment plant (WWTP) have some ability to retain MP 98,83%, however as the cycle would repeat itself several times the particle would become smaller the WWTP would no longer be efficient, discharging 227 millions of MPs abundantly fibers and fragments daily [26]. A single garment of clothes can produce > 1,900 fibers per wash. Fibers and fragments are then the most common types of MP’s in the ocean, with a value up to 80% [26].

10.1.1. Pollutants in our environment:

MP and NP are constant pollutants in our environment, they are found in the air, water, soil, hygiene care products and food (Fig. 3). They reach the environment through WWTP, rivers, and the most substantial way is through inadequate waste management and neglected human behavior [13]. It is proven that human actions are closely linked to the presence of MP and NP in the environment, with areas of more human activity experiencing an exponential increment in MP and NP debris [27].

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E.g.: Different samples sediments were taken in the Ross Sea in Antarctica, all of them contain MP and NP form 0.3 to 22mm in length. The vast majority of the MP and NP were fibers from pneumatic tyres from the Mario Zucchelli Base in Terra Nova Bay, with a population of 90 people [28].

Soil: Landfills were created as a strategy to dispose most the human waste. Most of the landfills cremate their waste, increasing the physical, chemical and mechanical reactions in the environment, as a consequence, MP and NP buried and sealed in landfills are subjected to severe environmental conditions. Leachate is a liquid form in the lower extracted of the landfills made of residues and chemical reactions. Leachate has extreme pH 4,5 – 9. The high salinity in the container, higher temperatures, microbial degradation and leachate would increase the breakdown of MP and NP, and when landfills would leak due to erroneous human action or an accident, MP and NP would leak with them into the nears soils.

When MP or NP are disposed in landfills or in the soil, the denser polymers are more likely to stay and be introduced into the deeper layers of soil. Nevertheless, the light polymers are more likely to be transported by wind, in this way the pollutants could be found in all the environments of human being lives [21]. Preliminary evidence validates that landfill is not the final sink for plastics, but a potential source of microplastics.

Air: MP and NP of light polymers could be transported through air, indicating that air could be a chronic exposure for human health.

In 2016 two studies were conducted, the first study it was demonstrated that approximately 3–10 tons of MP and NP fibers were deposited in the atmospheric fallout of Parisian every year (2500 km2) [29]. The second study, it stated thatthe concentration of MP in the air was increasing during the monsoon season, probably due to the strong winds that would lift the particles from the soil [30][31].

One of the biggest sources of MP in the air are MP and NP from synthetic clothes [32]. In 2012 the World Health Organization (WHO) declared that three million deaths were attributed to air pollution that year, stating airborne pollutants as an important source of health danger.

A person which suffers a chronic disease in the respiratory system would potentially develop more problems to the constant exposition of pollutants through the air, developing inflammation and oxidative stress, than a person which is not affected [32].

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In the medical literature has shown that MP and NP originating from inhalation or plastic prosthetic implants show effects varying from DNA damage, changes in gene and protein expression, cell clotting, necrosis, apoptosis, proliferation and loss of cell viability, oxidative stress, increased Ca ions, inflammation and bone osteolysis in humans [20].

Water: It is estimated that 13 million tons of plastics wasted get accumulated in the seas and oceans yearly [22]. MP and NP arrived at the sea in its majority through WWTP, fishing activities, recreational activities or through rivers, however, there is a small percentage of it 5-10% that does it through the air [33]. When MP and NP arrived in contact with water, these polymers would move vertically according to their composition and reach the bottoms of the sea and rivers interacting with the environment and

accumulation. MP and NP could travel horizontally creating big patches of debris that could be seen in the surface of the sea [27].

Hygiene care products: Microbead is the most used MP or NP in hygiene care products. They worked for a variety of purposes; sorbent in delivery of ingredients, film formation, exfoliation, viscosity etc.… MB

Fig. 3: Sources, transport, accumulations, and the fate of MPs in the environment. (P. Wu, et al.) [13].

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could be found in different percentages according to the product, ranging from 1% up to 90% of the composition.

E.g.: An exfoliative shower gel could have as many MB composing the cream, as plastic used to create the container it-self.

Food: The human diet is extensive and diverse. In this paragraph, it would be explaining different nutrients and its relationship with MP and NP. Examples of the constant chronal exposure that humans have in everyday life.

- Salt: MP has been found in commercial salts from 128 brands from 38 different countries over the five continents. Commercial salts are a route of chronic exposure to MP and NP te human health. This exposure could lead to long-term adverse for the health [34].

- Sea food: Due constant sea and ocean pollution, the animals living in it are inevitably contaminated with MP and NP. Bivalves like oysters and mussels get their nutrients through filtering the water around them. These animals could be found in the wildness however the vast majority of them are farmed by humans. Farmed mussels have a serious higher concentration of MP and NP (178 microfibers), compared to wild bivalves (126 microfibers). Due to their nature of filtration, the MP and NP would be retained in the tissue of the animal, and potentially translocated to other organs and systems such as the cardiovascular. Average European consumer could be ingesting per capita, e.g.: Belgium 72,1g per day. Once in the human gastrointestinal tract, translocation of MP and NP could cross the mucosa membrane and be translocated through the Peyer's patches to the lymphatic tissue [35].

- Water: It is essential for the survival of humans, in a late study it was found that plastic bottles of mineral water could be having concentrations of MP and NP, the polymers were found in all the samples. The main concentrations were Estimated Daily Intake for adults and children were 1,531,524 p/kg/ bodyweight/day corresponding to 40.1 mg/kg/bo dyweight/day and 3,350,208 p/kg/bo dyweight/day corresponding to 87.8 mg/kg/bo dyweight/day, respectively. The discovery of MP and NP were strongly correlated with pH of the water, density of the bottle and way of storing it [36].

Filters in WWTP have been demonstrated to be too big for the size of NP that are found in water. For this reason, the concentrations of MP and NP in treated water oscillated (from 338 ± 76 to 628 ± 28 L−1)

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implying that potable water could be an important chronic exposure rout of MP and NP into humans too [37].

10.1.2 Interactions with other elements

10.1.2.1 Bioaccumulation and bio-amplification

Bioaccumulation could be defined as the gradual accumulation of chemical substances in our organism. E.g.: heavy metals, bisphenol A (BPA), phthalates (PHT) etc.… This accumulation could take plaes in all beings, it occurs when the substance enters the organism in a faster rate than is excreted. More parameters affect the bioaccumulation; biological half-life of the pollutant, environmental levels and the mechanisms that the organism has in order to get rid of it.

Bio-amplification, or biomagnification is the concentration of any toxin in organisms and successively higher levels in the food chain. This situation takes place when the substance cannot be eliminated by natural processes. The pollutant cannot be excreted of the organism, and the substance concentration increases progressively as the food chain moves forward. E.g.: If the grass have been polluted with pesticides, there is a quantity of this pollutant in the grass, once the cow graze throw-out the green hills for hours the number of pollutants in each piece of grass have been multiply in the system of the cow, so more pollutants are in the cow's systems than in each piece of grass. The system goes one and on when the humans consume cow's product each day, increasing exponentially the pollutants in our organism that those compare to the cow [16].

This is the case of biological magnification that occurs with MP, NP and all the pollutants that could be adsorbed by them in the food chain, such as POP, BPA, HM, antibiotics and PHT. These chemical compounds could have serious effect on human health such as carcinogenic, teratogenic and mutagenic

[38].

Humans may be chronically contaminated with MP, NP and their pollutants through sea food, fish and other nutrients, with the exponentily aggravation of biomagnification [2]. Causing skin irritations, respiratory problems, cardiovascular diseases, digestive problems and reproductive deficiencies [2].

MP and NP are polymers that travel freely in the environment due to the forces of the same; the water currents and flows, the wind, or the human actions etc.… It is for this reason that MP and NP are capable to

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travel miles and miles away from their origin point [39]. An unexplored vector of pollution is the dissemination of MP and NP, is ballast waters from shipping. It is estimated that around 80% of the global comers is conducted through the seas, and the seas are at the same time the biggest dumpsters of MP and NP in the world. Ballast is the water used inside of the ships to neutralized external forces and make the boats more secured. The ballast water is changing constantly; it is estimated that around 12 billion tons of ballast water is mobilized through the biggest routes of comers of the sea every year [39]. Transforming in

this way MP and NP in the perfect means of transportations of pollutants from one ocean to another. Figure 4 presents the network analysis of bacterial communities in rocks, leaf and MP. Bacteria have the ability to secrete an extracellular polymer substance, which includes a pool of proteins, glycoproteins and glycolipids, that can form a matrix of structures enabling the attachment to different biotic and abiotic surfaces. This structure is denominated biofilms.

This is an evolutionary advantage that these microorganisms have in order to grow in hostile environments and still assure its survival [40].

Biofilms could be found in artificial and natural surface in the environment, e.g.: rocks and leave, however at the same time, medical devises (pacemakers, catheters, implants…) made in its majority out of plastic, causing uncountable infections and deaths [40]. It should be clarifying that several pathogenic bacteria

Fig.4: Network analysis of bacterial communities in rocks, leaf and MP. (X. Wu et al.) [77]

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were only detectable in MP and NP biofilms, but not in biofilms formed in natural elements such as rocks or leaves. Indicating that manmade polymers could be the biggest source of danger.

10.1.2.2 Absorption of heavy metals and pharmaceuticals

When MP and NP are exposed to the elements of the environment their morphology and structure changes. The aging process in which they are exposed, will eventually lead them to have more fissures and porous in their surface. Thus, the maturity of the MP and NP is more important in the adsorbing mechanism that the chemical composition of the polymer itself [38]. E.g.: UV light radiation, pH and temperature would increase the surface area in MP and NP and oxygen containing functions, would lead to the form of alcohols, acids, aldehydes, ketones and carboxylic acids [38].

These new changes in their chemical composition will lead to polymers negatively charged. This configuration is chemically unstable and would always tend to stabilize itself by absorbing particles positively charged, in this case heavy metals [1]. E.g.: PVC, PP, PET and PE have the ability to adsorb lead, copper and cadmium.

In a recent study conducted in 2016 it was stated that heavy metals on the surface of the plastic particles are up to 800 times higher than those concentrations found in seawater [1].

The biofilm explained in the paragraph above, plays a vital role in the absorption of HM. The biofilm formed on the outer surface of the MP and NP will intensify the adsorption of HM and POP. The size of the polymer would influence positively/negatively in its ability to adsorb POP, HM or other pollutants, smaller MP or NP, have been proven to have more adsorbing capacity that those bigger than them [41].

The new physicochemical properties (biofilms) of MP and NP would enhance the enrichment abilities of pollutants such as POP and HM, increasing in this way their pathogenesis [1]. HM have been classified by the WHO as harmful for the human's health, even at low concentrations due their high toxicity and possible carcinogenic effect [38]. Chronic exposure to the physical presence of MP has been linked to negative influence of survival and mortality on different planktons, which represents the first step in the trophic chain [20].

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The same mechanism that will facilitate the absorption of HM, also promote the adsorption of pharmaceuticals (Antibiotics (ATB), Analgesics, antipyretics…). One of the most vital and used pharmaceuticals for the human beings are antibiotics. The last century it was named the 'golden age of antibiotics' due to their development. Disease that before were consider mortal, could be effectively treated with ATB. Previously to the discovery of penicillium in 1928, 90% of the children that suffer from meningitis died. They are also important as common childhood diseases such as otitis could lead easily to encephalitis, and the most common act of cutting with a rose could lead to bacteremia [42]. In the United States alone it is estimated that current death due to antibiotic resistances are over 35,000 cases yearly.

If MP and NP have the abilities to absorb and transport all kinds of HM, biocides, BPA, PHT, flame retardants, endocrine disruptor chemicals, harmful alga bloom (HAB), ATB, and pathogens, therefore, these polymers have become ecosystems by themselves. Therefore, Threatening the survival of the environment, supporting the transmission of antibiotic resistance genes (ARG) between bacteria, and transforming MP and NP into natural reservoirs of ARG and metal resistance genes, facilitating the horizontal gene transference. Facilitating the plasmid, transposons, bacteriophages, insertion sequences and integrons dispatch in bacteria, compared to those in the natural environment [39].

HM could be influencing abruptly in the co-selection of antibiotic resistance in bacteria, making the combination of HM and ARG more pathogenic than just both of the pollutants separately.

This hotspot for HM and ARG would pose a serious emergency to worldwide human health and the trophic chain, with the possibility to create bacteria resistance to ATB and reach remote environments [42].

The misused of AB, is currently one of the biggest risks to human health. E.g.; In 2013, China discharge to the environment 53,800 tons of ATB [41]. The most common ways of ATB dischargement, are livestock farms, where ATB are used to enhance their growth or help in the prophylaxis of infections in the unsanitary crowded environments [42].

10.1.2.3 Bacteria, virus, algae

Stablishing the abilities of MP and NP to absorb and create a reservoir in itself, in which microorganisms could attach and proliferate, it's not a surprise that several studies have found in the aquatic environment the evidence of several bacterial, virus, fungal and eukaryotic colonizers in the pits and grooves of the MP and NP. The mentioned microorganism can create biofilms in the surfaces that they attached, in this case

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which an aggregation of microorganissm, HM, ATB, BPA, PHT, endocrine disrupted chemicals (EDC), ARG and other pollutants implicit or no in the polymer [2]. Figure 5a explains the role of MP as vectors for a range of chemicals and biota and Figure 5b presents the effects of MP on various aspects of human health and the environment.

MP and NP also have the ability to hold stagnant water, creating the perfect habitats for mosquitos’ larvae to transmit their pathogenic parasites such as Zika or Dengue. Increasing the spreading and flourishing of diseases [43].

Plastispheres have important ecological advantages compared to the non-modify environment (rocks, leaves…). Moreover, they are able to accumulate nutrients and they are a protective barrier against predators [44].

MP and NP could be working as artificial reservoirs and vectors for bacteria, viruses, fungi or other non-native species which are proven pathogenic for the ecosystem and human health. These polymers are capable of traveling notorious amount of distances, taking with them pathogens that are not autochthones to the new environment, creating a bigger danger than though in the first place.

Fig. 5a. The role of MP as vectors for a range of chemicals and biota. Fig. 5b. The effects of MP on various aspects of human health and the environment.

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One of the most critical examples of pathogenic bacteria found in MP or NP would be of the bacteria Vibrio species pluralis, a fecal indicator bacterium, that according to the WHO, it has estimated to infect yearly 1.3 to 4.0 million people and causes 21000 to 143000 deaths worldwide [2]. From 2011 to 2013 studies conducted the presence of pathogenic bacteria found in MP and NP found in different seas: Vibrio spp bacteria floating within MP and NP in the North and Baltic Sea, while V. vulnificus and V. cholerae were mainly in the Baltic Sea, V. parahaemolyticus and V. alginolyticusereas more predominately in the North Sea. [44].

Furthermore, the bacteria Escherichia coli, a potentially harmful pathogen, well known for causing urinary tract infections (UTI), diarrheas, septicemias, has been found capable of forming biofilms in MP and NP in water distributing pipes (PVC) of the cities. Stablishing that there is no need to practice activities related to water and being exposed to outdoors sources of water. Considering most of the people have access to running water in their houses. Humans could be in constant exposure to MP and NP and its biofilms implications. Similar results were found in 2014, when Aeromonas spp with a mortality of (28-63%), arcobacter causing serious diseases such as peritonitis, bacteremia, endocarditis, and Pseudomonas spp well known to cause severe cases of pneumonias, were find in high abundance on MP. Certainly, this situation could have deeper implications to human health and the environment than first assumed [40]. Additionally, MP and NP with their plastisphere are capable to adsorb HAB pathogens. A Harmful Algae bloom spp. that can severely decreaed the concentration of oxygen levels in the water. Destroying in this way all the ecosystem that lives in these waters. MP and NP through their plastisphere, are raising the possibility that HAB species would emerge [2] [40]. The states in which HAB acts are called blooms, each bloom is different, they could take days to months. After the boom is over, the place in which it happens would become a dead zone, no ecosystem could be form in there. HAB are induced by over exposition of nutrients in the water, more specifically nitrates and phosphates. The biggest discharge of nitrates and phosphates to the environment is due to the o malpractice of pesticies resources by humans. One of the biggest zones in Europe is located in the Baltic sea.

HBA have a direct implication in human health, due to the consumption of fish or sea food form areas contaminated. This could expose to thousands of toxins through the trophic chain. Resulting in diarrhea, amnesic shellfish poisoning, neurotoxic shellfish poisoning and paralytic shellfish poisoning. People are warned not to enter or drink water from HAB due to the development of serious gastrointestinal diseases [2]

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10.2 THE EFFECT ON ANIMALS:

10.2.1. The direct impact on animals:

Subsequently, the entire explanations in the paragraphs above about the qualities that MP and NP have as pollutants in the environment, it's not a surprise that the first being to suffer from these consequences are the animals in the lowest points of the food chain.

Through the recent years, MP and NP have been detected in 690 species of the marine environment, throughout the food chain, including fish, crustaceans, bivalves, mammals and plankton [9].

Plankton constituted the base of the trophic chain in the sea, plankton is an umbrella term to described organisms including bacteria, archaea, algae and protozoa. These organisms are floating in vast zones of water, including oceans, seas and fresh water. The importance of these organissm is vital, being the most primary livelihood of the trophic chain in the sea and part of the terrestrial ecosystems.

In 2017, a conducted study about microalgae concluded that the exposure of MP of PE, PS, PVC at a concentration of 0.1g/L reached 25.3%, 24.7%, 29.3% respectively decreased in photosynthesis efficiency and the chlorophyll content. Growth inhibition was impaired PS < PE < PVC, which state a precedent, that the toxicity of the MP could be related to the chemical composition [45].

Triclosan (TCS) is a broadly used antiseptic present in a huge variety of household goods: toothpastes, soaps, cosmetics etc.… Nevertheless, as a result of the poor treatment efficiency in the WWTS, concentrations of up to 14000mg/L being discharge daily to the environment. Triclosan has been categorized as EDC. The results in microalgae concluded that the toxicity of TCS had a significant inhibition effect on growth [45].

Soil invertebrates contributed accountable to the sustainability and the quality of the soil. They play a vital role in the mineralization, distribution and decomposition of organic matter and the release and storage of nitrogen in the environment. E.g.: Spp Enchytraeus critcus. During an experiment, the oligochaete was feed NP, leading to depression in feeding activity, the immune response was triggered, inhibition of growth, abrasion and obstruction of the digestive tract. The inhibition of growth could be related to the damage of the gut microbiome and their essential role in digestion and development of invertebrates. Decreasing the release and storage of nitrogen in the environment. Nevertheless, the microbe is subjected to the health condition of the host, and the nutrient that this one ingest. Indicating the MP and NP could be a potential

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risk for microbiota and host symbiosis [46]. Figure 6 illustrated an example of how MP could end up in the bivalves that the consumers would include in their diets.

Herbicides have been used through human history but is not until the end of the second great world when chemical synthetic herbicides are put into the market. In 2013, China reported to had released into the environment 1.8 million tons of herbicides. Becoming a serious water pollutant in the environment [47]. Glyphosate was been during a long perioe worldwide one of the most commonly used herbicides, due to its ability to work on a broad spectrum of species. Glyphosate has been constantly discharging at the environment, becoming a constant pollutant in our environment. MP and NP can adsorb herbicides in their structures. In 2015 a study measures the efficacy in which glyphosate will eliminate the colonies of M. aeruginosa spp. a classified HAB. The results proved that the absorption qualities of MP and NP were diminishing the available herbicide in the environment, increasing the M. aeruginosa spp. Blooming [47]. These effects, sets a vicious circle around MP, herbicides and the harmful pathogens. In one hand MP would adsorb the pathogens and the herbicides creating an excellent environmenr to cause the pathogen to become resistance towards the herbicide, and in the other hand the adsorption of herbicides by MP in the needed areas, would force humans to consume more herbicides and closing in this way the circle.

Fig. 6: Maphoto/ Riccardo Pravettoni; originally published by Marine Litter GRID-ADRENL . [66]

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Corals are marine animals of the invertebrate group. Corals are essential to create and maintain reefs, which are the ecosystems of millions of creatures. MP and NP negative effect on their species. It has been

reported that the specie Polillopora damocrinos, had attached MP at its filaments, even though it was not ingested by the animal, the contact develop bleaching, tissue necrosis, mechanisms of stress that would lead to secrete digestive enzymes and increased in chlorophyll, which could be explaedin by blocking the

natural light, forcing the coral to create more chlorophyll to compensate [48].

Mollusks are a group of animals, that serve as nutrients to fishes, birds and humans amongst other species. Mollusks get their nutrients through filtration; this specific process generates the fragility of mollusks against pollutants such as MP and NP. A 21-day text concluded that weight gain, growth and

hepatosomatic index, inducing oxidative stress in the liver and pancreas, of the species E. sinensis a crustaceans correlatedly decreadse with the increment of MP concentration in its environment [49].

Fish are a vital animal group in the food chain for humans, 4.3 billion people in the world related on fish to get their proteins in their diet. The biggest consumers of fish in the world are the countries in South East Asia, where the consumption of plastics is also the highest in the world. Figure 7 presented the possible physical and chemical effects of MP and NP in the health.

In 2016, the effects of MP and NP in the European perch were investigated, the study concluded that the exposition and ingestion of these polymers had desensitize the olfactory function of the fish and in consequence it has decrease its survival due to the inability to sense its predators [50].

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Accumulation of MP and NP would have a toxic effect in the gastrointestinal system of fishes, such as mucosal damage, increasine permeability, inflammation responses and the disruption of their metabolism [51]. The shapes in which MP and NP are manufacture play an important role in the disruption, retention and accumulation. E.g.: MP/NP fibers could be retained in the intestines for longer period than other shapes of MP and NP [51]. MP and NP fibers and fragments have a stronger toxicity effect in the guts, leading to cell necrosis compared to microbeads. MP and NP interact with lipids membranes and change their biological properties. This could explain the reason that disbalance in intestinal permeability, dysbiosis of natural protective microbiota, metabolism of lipids, and protein secretion can lead to diseases, such as inflammatory bowel diseases (IBD) and decreasing the normal absorption of nutrients, making MP and NP really dangerous pollutants for the human health [51].

Seabass spp. were exposed through their diet, during 40 days to POP and flame retardants in MP/NP, the results have shown a significant damage was inflected in liver metabolism, immune system and oxidative stress. ROS (oxidative stress) is accompanied by cellular damage of molecules such as DNA, with the possibility to cause genome instability and alterations in the biochemistry and carcinogenic effects [52]. An important parameter for the desorption of pollutants in MP and NP was the presence of digestive surfactants as, derived bile salts, found in the human gastrointestinal tract. If cholesterol-derived bile salts were present in the digestion more POP were released from the MP and NP [53]. Another example of bioaccumulation of HM such as mercury in D. lablaz juveniles due to MP and NP ingestion cause neurotoxicity, oxidative stress, enzyme deficiencies (LDH and IDH) and seveer damage to their health [54].

MP and NP and their additive can have the abilities to be transferred from one generation to the next one. In 2016, an experiment was conducted with zebrafish spp. Adults F0 males and females were exposed to NP through their diet. Four different groups included the control were created. In the first group only paternal exposure, in the second only maternal, in the third co-parental and the last one the control scenario. The results were impressive, the generation F0 shown significant glutathione reductase (an important enzyme) activity in their brain, muscles and teste, higher concentrations of ROS leading to oxidative stress and potentily cellular damage and apoptosis, however no changes in mitochondria function on the heart, gametes number of eggs or fertilized eggs. The offspring F1 from co-parental and maternal exposure shown

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parental and maternal exposure. The levels of glutathione reductase were diminished in F1 from co-parental and maternal exposure. Even though they have not been studies explaining the mechanism, one of the theories suggesst that the bioaccumulation of NP with high affinity for plasma proteins, including lipid transport proteins, vitellogenin, in and zona pellucida, facilitating in this way the transfer of NP to F1. Explaining the reason of no affectation only with father exposition. This discovery could have an immense human implication if the same mechanism of transfer could be done in our metabolism. This study

demonstrated that NP are able to bioaccumulated and be transferred from mothers to their offspring’s, and this exposition was able to change and alerted the antioxidant system in the F1 subjects [55].

Being in big patches at the surface of the sea, MP and NP are often confused with nutrients and would inevitably enter the systems of the animals at the top of the food chain, such as mammals and birds. Seabirds often have been used as markers for MP pollution. In the last research, out of 263 Seabirds collected 79,0% of them contained plastic debris in their gastrointestinal tract. Most of the debris were fragments 83,6% of the total [56]. Several studies had demonstrated that once the MP and their additives have been consumed, they can bioaccumulate and translocated between tissues. E.g: MP of (3 μm and 9.6 μm in size) where found in the haemolymph and haemocytes, developing a gangliocytoma formation and decreasing the lysosomal membrane stability in M. edulis spp. after three days of exposure. This would directly endanger the human health [56].

10.2.2 Impact in the trophic chain:

It is estimated that in 2025 it would be 1 ton of plastic per every 3 tons of fish in the sea, however if the production and waste management continue in the same way, in 2050 the weight of plastics in the sea would overcome the fish weight [57]. The United Nations and the European Union in 2013 reported that more than 50% of plastic compositions were chemicals hazards [52].

In the scientifically studies on MP and NP there is not an unilateral mesh regulation to establishing the amount of MP and NP/L in the water, each study uses its own parameters, however recently the tendency is to believe that large mesh as 300–350 μm could be neglecting MP and NP in the environment,

underestimating the concentrations of MP and NP in the environment, and in consequence underestimating the negative effects in the human health [68].

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The breakdown of MP and NP increased the likelihood of being ingested by the organism in the surroundings, because the animals search nutrients using the chemoreceptors of their olfactory and gustatory cues. When these polymers start to disintegrate, they could release a chemical component (dimethyl sulphide) which odor resembles the organic matter that is present in their everyday aliment. Incrementing the entrance of MP and NP into the trophic chain [59]. Figure 8 delineated the potential health effects for the bioaccumulation and biomagnification though the diet of MP and NP.

Afterall humans are at the top of the food chain, we are omnivores capable of getting our nutrients from different sources in the trophic chain. E.g.: Vegetables, fruits, legumes, seafood, fish, meat etc…. This varied diet could be a silence chronic pollutant exposure towards our health due to the bioaccumulation of toxins in MP and NP.

There is a 10% of the world’s population that dependent of fisheries for their live hood, it is estimated that fish and sea food made for 13.8% and 16.5% of proteins in their diet. The poisoning of these aliments may lead 4.3 billion people in specially growing countries with a protein deficiency, leading to malnutrition and famish. This number would increase to the already 795 million people suffering from malnutrition in the current world.

Fig. 8: Potential health effects resulting from the bioaccumulation and biomagnification of MP and NP. M. (Carbery et al.) [59]

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As an example, the amount of MP that was found in 2014 at shorelines were 100,000 per m2 [24]. Most of the biggest farms of sea food and fish are near the coast. This is an alarming finding. It is estimated that European seafood consumers could be ingesting up to 11,000 MP/NP particles per year.

Since humans had become the absolute consumer in the aquatic world. Consumption of MP or NP seems tangible, due to the bioaccumulation in our diet. This theory is supported, due to the fact that most of the species that humans eat had been found to contain MP and NP within themselves. Although at most of the MP and NP were found in their gastrointestinal tract, toxicity could be expected from translocation towards other organs and remain there causing a chronic exposition, e.g.: the species Mytilus edulis frothe m North Sea and Crassostrea gigas spp. from the Atlantic Ocean had within their soft tissue MP and NP load of 0.36 ± 0.07 and 0.47 ± 0.16 per gram [9].

POP and EDC are other of the biggest complications of MP and NP consumption, these chemical

components would leach from the polymers causing in the surrounding tissues of the animals and humans acute and chronic harmful effects [35].

MP and NP cause throughout the food chain adverse effects such as growth inhibition, behavioral

disorders, neurological toxicity, reproductive dysfunction, immunological dysfunction, alteration in gene expressions, disruption of the endocrine system, feeding disorders, creation of oxidative stress through free radical generation, in marine organisms, some of them mammals [60][52].

It is only logical to raise concern if these new pollutants MP and NP are a risk for the health of humans too.

10.3 THE EFFECT ON HUMAN HEALTH:

10.3.1 Human exposure:

In the previous chapter it was explain the possible pathways that humans could be consuming MP and NP thought the food chain, or the dangerous pollutants that could be carried within themselves. In this chapter, it would be described the human health impact towards MP and NP.

Based on 26 studies and over 3600 samples of the American diet, it was estimated that the intake of MP and NP was between 39000 to 52000 particles depending on the age and sex per year, this data would be

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only taking in consideration the polymers consumed through the diet. Estimating that the diet includes seafood, sugar, honey, salt, fish and alcohol which are some of the nutrients found to be caring MP and NP. Nevertheless, the human diet is composed of so many other nutrients such as meats, dairy, grains and vegetables that now a days are lacking of scientifically studies about their possible implication in the pollution of MP and NP, difficulty the proper estimation and dangerously underestimating the consumption of polymers throughout the diet [61]. The estimation would increase if water sources are taking toin

consideration such as tap water 4000 MP yearly or 90000 MP if the source is from bottles of water.

Moreover, these past estimations are not taking toin consideration the possible translocation of MP, NP and POP that the plastic packaging that most of the foods and drinks that we consume have on them [61]. E.g.: Antimony (Sb) a chemical element that is used in the commercial production of PET plastic bottles, has shown that under high temperatures of (60 – 85*C), the Sb would be released in the bottle and diluted in the drink. Consumption of Sb could potentially lead to nausea, vomiting or diarrhea. If the storage of the plastic bottle or any plastic packaging that we consume through our diet is not optimal, the consequences towards our health could be critical [62].

Additionally, if inhalation is taking toin consideration for the calculation, having in mind that microfilaments are one of the most common MP and NP found in the environment. The estimations increased to 74000 and 121000 according to age and sex [61]. As an example, it would be estimated that throughout the diet children would be consuming daily from 106 to 113 MP or NP, and adults 126 to 142 polymers.

The biggest pathways in which humans are consuming MP and NP are through the diet, water, air and skin adsorption.

The air could be a potent vector for pollutants in our system. It was estimated that MP concentratioisre 2.09 to 17.75 polymers per M2 of air [63].

Dermal adsorption is without doubt the most unstudied pathway of exposure to MP and NP. Absurdly; water, cosmetics, pharmaceuticals, personal care products, medical equipment and clothes are exposed in a daily base to our skin [63][62]. The skin is the biggest organ in the human body, having a dimension of up to 2m2 and weighting up to 3kg. Howeverr for the MP or NP to cross the dermal barrier, the polymers need to penetrate the sriatum corneum, which only allow particles below 100nm, this would result in NP being the only polymers capable to cross the barrier and translocated within it [62].

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10.3.2 The impact of MP and NP in human health:

In this paragraph it would be described the current studies that establish a clear relationship between the consumption of MP and NP and the consequences fhe human health.

As mention before, the possible pathways in which MP and NP enter our body are oral (food, water …), dermal (cosmetics and personal care), inhalation (pollutants in the air and gases) or parental (medical devices).

It has been proven that positively charged NP shown more effects in the physiology of the cells, that negatively charged. Also, the size could be an important factor of pollutions. The smaller the polymer in this case NP, could easily penetrate the cell membranes and successfully accumulate in the cells [64]. Only

MP and NP with size <20 μm would be able to penetrate organs, however the body has barriers (placenta, blood-brain barrier) that only NP of (0.1 > 10 μm) are capable to access. Transforming the NP in the most dangerous polymers [65]. Figure 9 illustrated the correlation between size and accessibility in mammals of MP and NP.

The most common pathway in which humans consume MP and NP is through the diet. It has been speculated that MP > 150 μm will not probably be absorbed while MP and NP < 150 μm could be potentially absorbed and translocate from the guts to the lymph and circulatory systems, developing in a systemic exposure. The MP and NP once ingested would be trapped by the mucosa of the guts and

endocytic pathways would translocate them [63]. It is estimated that the majority of the translocation would happen in the Peyer’s patches of the ileum and then to the lymphoid system [63]. Other non-so used

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pathway of translocation would be the persorption route, where MP and NP can pass through gaps in the mucosa of the gastrointestinal tract and the desquamation zones. In this case the macrophages would uptake them and translocate the particles to the lymph nodes. In both systems, the translocation would secondary affect other organs e.g.: kidneys, liver, brain, heart, uterus…) impactine human health with

cardiopulmonary responses, alteration of the metabolism, inflammatory responses, oxidative stress, changes in the gut microflora and decreased in the reproduction [66].

10.3.2.1 Microbiota in the gastrointestinal tract:

The human gastrointestinal system contains trillions of microorganisms, including bacteria, fungi and other microbes. These microorganisms out number all the cells in the human body for 10 to 1. However, its weight it's only 1 to 3% of the total body mass, this is due to its diminutive size. This call gastrointestinal microbiota, are in symbiosis with humans. They help regulate and controlle some of the most vital necessities for humans. E.g.: They control the digestion, benefit the immune system, activated the mechanism of pharmaco-macrobiotics, cooperate in the gut brain axis (regulating the central nervous system, neuroendocrine system, and neuroimmune system). Not wih standing, the symbiosis between humans and beneficial microorganissm could be in danger due to MP, NP, POP and EDC. Creating a dysbiosis state and triggering the onset of chronic diseases, infections and altering the microbiota's capacities. Figure 10 demonstrated the mechanism of gut dysbiosis by the effect of MP and NP.

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It has been explained throughout this chapter the complications that MP and NP could cause once they enter the gastrointestinal tract of humans, causing immune and inflammatory responses, these processes are often associated with shifts in the composition of gut flora communities [67]. One of the most followed theory is that the MP and NP would trigger an oxidative state, and this new hostile environment will promote the appearance of new microbiota. E.g.; Actinobacteria spp. and Proteobacteria spp. Another theory supports that the inflammatory state would rise anaerobic respiratory terminal electron acceptors, which would subsequentially favor the growth of anaerobic bacteria spp, e.g.: Enterobacteriaceae spp. The MP and NP would not only impair sufficient nutrition for the host in this case the humans, but

inevitably the sufficient nutrients for the microbiota. Decreasing the microbial gene expression linked to the host diet [67]. In adults it has been proven that rapidly shift in the microbiota communities has been found in response to dietary changes and then immediately recover its original composition unless the changes are happening in a chronic period of time, which is the case of MP and NP. Consequently, exposure of MP and NP throughout the diet since infancy towards adulthood would impact the compositions of the gut microbe, developing in a non-balance microbiota.

As mentioned previously, the mechanical disruption of the mucosa, the stimulation of the immune system, are two pathways that are interconnected, and that would constantly influence one another. The immune system would control the homeostasis between the symbiosis, and the microbes would play its part in maintaining the mucosal barrier.

The microbiota (Bacteroidetes spp. and Firmicutes spp.) with the creation of short chain fatty acids

(SCFA), during the fermentation of fiber, would influence immensely the immune system. Short chain fatty acids would be able to participate in gene regulation of the metabolism of B cells and immunoglobulin A (IgA) [67]. As mention before, the microbiota has effects on hormones secreted by humans, bacteria in the microbiota process a hormone receptor, given that MP and NP could be carriers of EDC, this could be another pathway in which MP and NP could harm the human health [67].

All things considered, the ingestion by humans of MP and NP would lead to dysbiosis. Leading to malnutrition, inflammation, greater exposure to pathogens, exposure to endocrine disruptors and POP. Erroneous colonization of the gastrointestinal microbiota would have severe consequences for human health, impairing the gut mucosal barriers, which if continues to develop during chronic periods it has been linked to diabetes mellitus type 2, allergies and irritable bowel syndrome [67]. As mention previously, NP < 150 μm could be potentially absorbed and translocate from the guts, however, this situation changes

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when the person is already suffering from an inflammatory bowel disease, showing to increase the transport and the permeability from 0,2% in healthy controls up to 0,45% in people suffering the diseases [62]. Establishing groups of risks in the pollution of MP and NP.

10.3.2.2 The central nervous system:

Only NP of (0.1 > 10 μm) and hydrophobic molecules are capable to cross the blood-brain barrier. This natural boundary is designed to be highly selective to protect the brain against toxins and to ensure to neuronal homeostasis [68] [32].

Only in vitro with human cells and animal studies has been conducted to investigate the possible effects of MP and NP in our central nervous system.

One of the most study pathways in animals if the translocation through the olfactory mucosa and later on olfactory nerve. In a study using fish, the PET Nano-plastics were reducing the acetylcholine activity in the synopsis and in consequence the neurotransmission [32].

Human model in vitro with MP (10 μm) and NP (40–250 nm) demonstrated that PP were able to cause oxidative stress in neuronal cell lines aned stablishing the possibility that high concentrations of NP in the CNS could cause adverse reactions as inflammatory responses, plaque deposition or even behavioral changes [28] [65].

A study in vitro with epithelial and cerebral human cells demonstrate that the exposure of microsphere (10μm) could induce high production of ROS [9].

10.3.2.3 The skin:

There are no so many studies that focus in the effects of MP and NP even though is one of the main routes of absorption (cosmetics and personal care products usually contain microbeads). There is one in vitro study that studies the effects of polystyrene NP in Hs27 cell lines of human fore skin. This study focusses on the ROS analysis detected in the human cells with NP alone and NP added the extract of crocus sativus spp. The results shown DNA damage, with an increased in the formation of micronuclei and nuclear buds.

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added together, compared to the increaed in ROS production with the only used of NP. The study was conducted using cytokinesis-block micronucleus and scanning electron microscopy.

The results reported that concentrations of 75 μg/mL at 48h of exposition, the polymers aggregated and enhanced the interaction with cell proliferation. These reactions where not occurring at 24h, demonstrating that chronic exposition is an important risk. ROS production was recorded with the minimum

concentrations of 5 μg/mL. High exposure time seems an indicative of the genotoxicity and damage inside of the cell that NP could cause. When NP and Crocus sativus spp are put together, the results have shown a ROS production in the first 30 minutes, nevertheless after this first minutes the production would decrease due in great part to the detoxification system that the flavonoid and the immune system puts in place. Showing that Crocus sativus L. could have a preventive oxidative property [69].

10.3.2.4 The placenta:

The placenta is a temporary organ that would grow in the uterus of the female mammals during pregnancy. The placenta would act as the natural barrier between the mother’s blood system and the fetus. Even though the medical literature proposed that the placenta is an efficient barrier preventing nanomaterials such as NP to enter the fetus. NP could be accumulating in a bigger rhythm that are removed, interfering in this way with the normal developing of the organ. If the proper functioning of the organ is in danger, the secondarily affect in the embryo or fetus could develop in a critical condition.

Unfortunately, only animals and ex-vivo human studies have been conducted. These studies focus in oral and I.V administration.

One study exploring animal maternl -fetal transfer by I.V administration and fluorescent polyglycidyl met- crylate NP, find that presence of NP where in the decidual and trophoblast giant cells, also NP where found in the placenta using confocal microscopy. Fluorescent NP were detected in the placenta inside of the lacunas after 5 min of a single dose (NP70nm) of I.V. After four days of the administration, no signs of NP were found in the placenta [70].

In contrast the data reported by an ex-vivo study in humans, found that NP up to 240 nm would be able to cross the placenta [70]. and access the fetus and amniotic fluid.

Figure

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References

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