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The Health Implications of Plastic Bioaccumulation and The Potential to Enhance Biotransformation Using Herbal Medicine and Nutritional Supplements

The largest global consumer of oil is the United States (US) military, consuming 100 million barrels of oil per year [2]. Despite overwhelming evidence of carbon-fuelled climate change and billions in subsidies for alternative technologies, global oil consumption will reach 100 million barrels per day, more than twice what it was 50 years ago, with no sign of abating [3]. The US alone uses 330 million barrels of oil per year in plastics production alone, [4] three times the US military use. ISSN: 2644-2957 DOI: 10.33552/OJCAM.2020.03.000567


Microplastics contain and absorb toxic chemicals
Microplastics are a vector for heavy metal contamination from the marine environment [6,7]. Microplastics attract harmful pathogenic bacteria in sewage and contain and absorb toxic chemicals. More than 50 persistent organic pollutants (POPs), specifically polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) are found in the five most common types of plastic [8]. POPs are also called persistent toxic substances (PTS) [9].

Plastic in Tap Water Globally
Billions of people are drinking water contaminated by plastic particles with 83% of samples found to be polluted. The US had highest contamination rate, at 94%, with plastic fibres found in tap water at Congress buildings, ironically the US EPA headquarters and Trump Tower in New York. Lebanon and India had next highest rates. European nations including UK, Germany and France had lowest contamination rate at 72%. The average number of fibres found in each 500ml sample ranged from 4.8 in the US to 1.9 in Europe [10,11]. An Irish study (June 2017) found microplastic contamination in a handful of tap water and well samples "We don't know what the health impact is and we should follow the precautionary principle so we can find out what the real risks are," said Dr Anne Marie Mahon at the Galway-Mayo Institute of Technology (GMIT) [12].

Plastic in Bottled Water Globally
The Orb study (Orb Media U.S-based non-profit journalism organisation) tested 259 bottles from 19 locations in 9 countries across 11 different brands were found to contain on average 325 plastic pieces for every liter of water. Scientists used Nile red dye to fluoresce plastic particles in the water, developed by Dr Andrew Mayes, University of East Anglia scientist. Nestlé Pure Life was worst offender; concentrations as high as 10,000 plastic pieces per liter. Of 259 bottles tested, only 17 were plastic free [13]. The contamination is said to be partially coming from packaging and/ or bottling process [14]. The most common plastic fragment was polypropylene plastic used to make bottle caps. Polypropylene is number 5 in triangle and considered safe. The study was not published in a journal, nor has been peer reviewed. A second unrelated Story of Stuff Study examined 19 bottled water brands in the US, also found plastic microfibers were widespread. Plastic fibers in bottled water brands are twice as high as those found in tap water [15]. See (Appendix) for brands Orb Media and Story of Stuff tested.

Plastic Water Bottles
Plastic water bottles are made from polyethylene terephthalate (PETE recycling code 1). This symbol is normally also found in soft drinks. PETE does not contain BPA/Phthalates, but studies find the endocrine disrupting chemical (EDC) antimony, a toxic phthalate 'plasticiser' used to make plastics flexible, leaches from PET bottles placed in heat for prolonged periods (16). Reusable plastic drinking water bottles are or more generally now, were made from polycarbonate (recycling code 7). Polycarbonate is made of BPA [17]. Investigations show in some cases, BPA-free PETE containers might leach of estrogen like chemicals [18].

Sources of Environmental Microplastic
Washing acrylic, polyester and nylon Plastic derived, acrylic, polyester and nylon persist in the environment. Synthetic clothing that ends up in landfill soaks through the land, into the water table and into our drinking water.
Alternatively, it ends up in our sea and evaporates into our clouds and back into our drinking water. One truck load of used clothes goes to landfill every second. One truckload of plastic enters the sea every second. By 2050 scientists estimate there will be more plastic in the sea than fish [19]. Acrylics are by far the worst offender.
When acrylics are washed in washing machines, the average load of household washing shed 750,000 microplastics per wash, 5 times more than polyester-cotton. When drying synthetics, we are venting microplastic straight into the atmosphere [20,21].

Burning plastics
Burring plastics releases endocrine disrupting cancer causing dioxins and furans the most toxic chemicals known to humankind [22].

Plastic in teabags
A recent study indicated that steeping a single plastic teabag at a brewing temperature of (95 °C) releases approximately 11.6 billion microplastics and 3.1 billion nanoplastics into a single cup of tea.
The composition of the released particles is matched to the original teabags (nylon and PETE). A toxicity assessment performed by the researchers showed that exposure to the plastic particles released Page 3 of 9 from the teabags caused dose-dependent detrimental behavioral and developmental health effects [15]. Non-biodegradable plastic contains teabags have been added to the municipal compost for decades.

Extent of Plastic Contamination in Food and Air
Plastic in beer, salt and well water A German study found plastic fibers and fragments were found in all 24 beer brands tested, as well as honey and sugar. The study concluded the average person ingests 5,800 particles of plastic per year from beer, salt and tap water, with largest contribution coming from tap water (88%) [10].

and 10 tons of plastic fibers fall on Paris per year
Microplastics and nano plastics in our oceans evaporate into the sky and in our atmosphere providing a source of both outdoor and indoor air pollution. A recent study investigating the atmospheric fallout of microplastics estimated between 3 and 10 tons of plastic fibers are fall on Paris per year [24]. In relation to plastic POPs the NHANEs study measures;

Evidence of Plastic in Humans
• Serum dioxins, furans and PCB • Urinary phthalates and BPA [25] One NHANEs study found 91 POPs analyzed in blood samples and concluded that one tenth of the US population may have ≥10 POPs each at concentrations in the top decile [26].

Plastic in human stools
Nine different plastics have been found in all human stools tested [27].

Nanoplastic passes the BBB in fish
Science has shown that nanoparticles or nano plastic passes the blood-brain barrier (BBB) in fish resulting in behavioural disorders and brain damage [28]. Most of the information we understand about the detrimental health effects of come from studies conducted in fish. The WHO is only just now looking into the health effects of plastics n humans.

Main Text
The WHO launched a health review on microplastics in drinking water to:
Close to 800 chemicals EDCs, capable of interfering with hormone; • Receptors • Synthesis

• Conversion
Three strands of evidence give strength to concerns over EDCs:

1.
High incidence and increasing rates of endocrine-related disease in humans.

2.
Observations of endocrine-related consequences in wildlife populations.

EDC Diseases and Disorders
I. Female and male infertility: BPA can interfere with hypothalamic-pituitary axis (HPA), such as increasing hypothalamic gonadotropin-releasing hormone (GnRH) secretion and promoting pituitary proliferation [31].

II.
Low sperm count: In up to 40% of young men.

XI.
Atopic disorders: Phthalates and BPA exposure are associated with allergies, asthma and atopic dermatitis [35].

Lowered vaccine response
A study of two birth cohorts in the Faroe Islands, where diets may include whale blubber contaminated with PCBs, suggests exposure to PCBs may reduce immune response to childhood vaccinations [36]. Another study in Dutch preschool children measured humoral immunity by antibody levels for mumps, measles, and rubella after primary vaccination and found that prenatal PCB exposure measured as a higher dioxin toxic equivalent (TEQ) was associated with an increased number of lymphocytes, T-cells, and cluster of differentiation (CD) CD8+ (cytotoxic), CD4+ (memory), T-cell receptor (TcR) and CD3(+) (activated) T cells and lower antibody levels to mumps and measles at preschool age [37].

Heath implications of microplastics according to the WHO
It was widely reported recently that the WHO report referred to find no evidence of a current danger from microplastic [38]. This is not quite factual. In the first instance the WHO report is about micoplastics in drinking water only. Microplastics are as previously

Mitigate Environmental Exposure
Mitigation strategies include avoiding drinking water in plastic bottles and using an end stage water filtration unit to filter public drinking water supplies. Avoiding plastic incineration will also mitigate exposure. Phthalates are typically found in industrial solvents and lubricants, additives in the textile industry, in pesticides, floorings, roofing, wall coverings, cables, clothing, packaging materials, personal-care products and toys [41]. BPA is used in polycarbonate plastic and epoxy resins manufacture. BPAderived products used in safety equipment, baby bottles, protective coatings inside tin cans and as composites and sealants in dentistry.
Exposure to BPA results primarily from ingesting contaminated food [42].

Measuring the burden of human exposure
BPA-glucuronide has terminal half-life of <6 h, is rapidly excreted in urine and can be used as a biomarker of exposure to BPA. Exposure to these phthalates can be assess using custom synthesised reference standards of specific oxidised metabolites of Diisononyl phthalate (DINP) and Diisodecyl phthalate (DIDP).
Phthalates are quickly metabolised and excreted in urine [43].

What Happens After Exposure?
After exposure, EDCs enter the body. Nano plastics reach the blood systemic circulation and distribute into various body compartments and penetrate cells [44]. Plastic too big to pass through gut wall still pose a risk as this plastic carries hydrophobic POPs /EDCs of smaller molecular size capable of penetrating cells [45].

Understanding Biotransformation of Plastic
Research into human biotransformation and elimination systems continue to evolve.

Phase 1 and II Liver Detoxification Pathways
Liver detoxification is a misnomer as Phase 1 and II Liver Detoxification Pathways also occur in kidney, intestine, lung, skin, prostate, and brain. In medical terminology toxicity is called bioaccumulation and detoxification is called biotransformation.

including sulfotransferases, glutathione-S-transferases (GSTs)
are also involved in BPA conjugation [51]. A fraction of absorbed BPA may distribute to body storage site (s) such as adipose tissue, followed by a slow, low-level release of BPA into the bloodstream [43].

Dioxins, furans and dioxin-like PCBs
People vary in capacity to eliminate TCDD. The elimination rate is much faster at higher than lower levels [58]. TCDD induces a few CYP450 enzymes systems [59]. Accumulation of POPs, dioxins [59,60] and furans induce cytochrome P450 enzyme systems [61].

Phase I -Modification
Phase I reactions occur in the liver and are catalyzed by

Modification pathways involve:
• Oxidation is process of being oxidised (combining chemically with oxygen/rust).
• Reduction involves gaining of electrons by one atom involved in reaction.
• Hydrolysis involves a chemical breakdown of a compound due to a water reaction.
• Hydroxylation involves introduction of a hydroxyl group

Induction of Phase I (over activity)
Certain metabolites of Phase I reactions are readily excreted.
Many Phase I products are not rapidly eliminated and undergo subsequent Phase II reactions. If not adequately supported or when excessive POPs exist, Phase I is induced producing high levels of damaging free radicals. If these reactive molecules are not metabolised by Phase II conjugation, damage to proteins, RNA, and DNA occurs. Phase I can turn a nontoxic molecule into a toxic (mutagenic/carcinogenic) molecule hence contribute to early ageing and cancer pathogenesis [66,67].

Phase II -Conjugation
In the hepatocytes toxic metabolites undergo biotransformation and are conjugated with glutathione (GSH), sulphate, glycine or glucuronic acid. These reactions are catalysed by a large group of broad-specificity transferases, the most important being glutathione S-transferases (GSTs). This makes the toxin or drug water-soluble, so it can then be excreted via bile, urine and sweat. and catalase (CAT) [68]. The glutathione S-transferases (GST family) are activated through cysteine, glutamic acid and glycine to make glutathione. BPA, [50] dioxins, furans and PCBs undergo glutathione conjugation [63].
Sulphation is involved in detoxification and hormone regulation.
Glycine conjugation: Co-factor: Glycine is catalysed by glycine N-acyltransferase is an important metabolic pathway responsible for maintaining adequate levels of free coenzyme A. Phthalates, [56,57] dioxins [65], furans and PCBs undergo glycine conjugation.
Milk thistle is rich in phytochemicals that can modulate UDPglucuronosyltransferase (UGT) Phase II enzymes [78].
The hydroxycinnamic acid cynarin stimulates glucuronidation conjugation. Artichoke has potent antioxidant activity and reduces toxin-induced reduction of glutathione reserves [80].

N-acetylcysteine
N-acetylcysteine (NAC) is a precursor to L-cysteine that results in GSH elevation biosynthesis. NAC increases GSH conjugation and is a powerful antioxidant/free radical scavenger [88].

Grapefruit
Grapefruit contains the compound naringenin which inhibits CYP450 and induces Phase II [54].

Conclusion
As the awareness of microplastic contamination grows, so too does global concern regarding the health implications. Whilst reproductive and developmental abnormalities linked to EDC exposures in birds, frogs, seals, polar bears, marine mollusks, and other wildlife species are documented, the health effects of chemicals associated with full exposure from the whole gamut of endocrine-disrupting ability in humans including organochlorine pesticides, PCBs, BPA, phthalates, dioxins, and furans is yet to be ascertained, with the WHO report identified knowledge gaps. Some in the medical fraternity dismiss detoxification as quackery.
What is true is that research into human biotransformation and elimination systems continues to evolve. Both mitigation strategies and research into pharmacognostical approaches that support