HighlightsIncreases in plastic production and use have ledto widespread environmental pollution[8, 10] andpresent concern for humans and other ecosystemmembers which come into exposure with micro- andnano-plastics[7, 10].Ingestion and inhalation are the major routes of ex-posure for humans and animals[7].Depending on dose, particle size and material, var-ious negative effects are seen[1, 2, 7, 8, 10] whichare thought to potentially lead to increased vulner-ability to neuronal disorders[8] such as Parkinson’sdisease[5], learning inhibition[6, 11], and behavioralchanges[8].BackgroundSingle-use plastics such as polyethylene, polypropylene,polystyrene, poly-vinyl-chloride (PVC), polyamide andpolyethylene terephthalate (PET) have contaminatedthe environment, with about 10% of all plastics producedeventually contaminating marine environments[8]. Ap-proximately over 5 trillion pieces of plastic are floatingin our marine environments, excluding fresh surface wa-ter and ocean floors[8]. Micro- and nano-sized particles(MNPs) have also been identified in air pollution[10].The bulk degradation of plastics into our environmentmarks a new era for humanity, to the extent that plasticparticles have been identified in consumable products[10]such as seafood. As plastics degrade into MNPs, theycan become airborne and enter our waterways and foodchain[10]. Additionally, exposure through ingestion, in-halation, and dermal contact present additional vectorsfor human exposure[7]. Figure 1: Plastics degrade into micro- and nano-particles, acting as vectors for delivery of toxicmaterials[10] with profound negative conse-quences.There has historically been a lack of knowledge on ma-jor additives of concern in the plastic industry, and whatoccurs once they are disposed of into the environment[1].The plastics industry uses numerous toxic and dangerouscompounds in plastics production such as flame retar-dants, lubricants, dyes, and various fillers[1] which canhave negative effects on human health[1, 7, 8] as well assurrounding marine and animal life[2, 6].Inhaled nano-particles can affect neurons and depositin the brain, eliciting changed behaviour in animals[6].Animals with MNPs in their environment such as fishand rodents are also affected, with changes in biochem-ical expression[2], gut microbiota cross-talk[4], and neu-ronal damage[9].Animal models used to study human diseases haveshown concering effects such as brain abnormalities forprogeny with maternal exposure[3], negative learningand memory effects due to oxidative stress[11], inductionof Parkinson’s disease-like neurodegeneration[5], and in-duction of microglia causing neurotoxicity[9].Mode of Action and PharmacologicalEffectsIngestion is the primary route of human exposure tomicroplastics, with about 50,000 particles ingested perperson per year through contaminated food or mucousmembrane inhalation [7]. It is estimated that of all par-ticles under 150μm which can cross the gastrointenstinalepithelium, that 0.3% are absorbed[1]. These particles,which penetrate the body through intestinal M-cells orare absorbed due to their small size, can lead to an in-flammatory response and disruption of gut membranesand microbiota[7].Figure 2: Overview of neurotoxic effects of micro- andnano-plastics[8]. Areas with dashed lines orquestion marks warrant further conclusive re-search.Inhaled microplastics range from 100-200 per personper day, with deposition inside the respiratory systeminfluenced by particle size and density[7]. Clearance bymacrophages or entrance into the circulation and lym-phatic system are possible routes through which theMNPs can further enter the body[7]. If the particlesare not cleared, they can release chemotactic factorsand cause chronic inflammation[7]. Particles smaller than 1μm can cross into our bodies through lung mem-branes, and fibers of 15-20μm cannot be removed frommacrophages in the lungs[1]. Even smaller particles inthe nanometer size range can induce toxic effects andinfluence cell division and gene expression[1].Recent in-vitro studies have examined the presenceand effects of metals such as chromium, silver, titanium,and aluminum, with demonstrated negative effects onhuman brain and HeLa cell lines[1].Additionally, engineered in-vitro studies examiningthe absorption and translocation of nano-plastics in hu-man brain and HeLa cell lines have seen positively-chargenano-particle interaction with secretion film, influencingcellular vitality, inducing apoptosis, and exhibiting othercytotoxic effects[1].Inhaled nanoplastics from polystyrene (PS) of 80 nmand smaller were able to be deposited in the brainsof mice, and resulted in less activity compared to in-haled water droplets – likely due to inhibition of Acetyl-cholinesterase (AChE) activities[6, 11]. Interestingly, af-ter treatment with vitamin E as an antioxidant agent,the learning and memory abilities of the mice was re-stored and release of neurotransmitters rebounded[11].Additionally, in-vitro studies on zebrafish with realis-tic parameters of freshwater pollution show an increasein AChE activity[2], however, they also show alteredneuroblasts and an increase in apoptotic and necroticerythrocytes[2]. Despite the opposing effects on AChEbetween mice and zebrafish, both still exhibit negativeneuro- and cyto-toxic symptoms as a result of MNPsexposure. This highlights also the need for more conclu-sive studies in models which are of clinical relevance tohumans.Additionally, PS particles of 50 nm and smaller arepassed onto progeny during postnatal stages in micethrough breast milk, and can accumulate in a dose-dependent manner in the hippocampus and cerebellum- increasing the risk for cognitive defects, but not of lo-comotive and emotional defects[3].50 nm PS nano-particles were also examined in micein regards to Parkinson’s disease. It was found throughRNA sequencing that there were cell responses specific tothese particles which induced mitochondrial dysfunctionin excitatory neurons, and inflammatory turbulence inastrocytes and microglia[9], dysfunction of proteostasisand synaptic-function regulation in astrocytes, oligoden-drocytes, and endotheliocytes[5]. These transcript-levelresponses are thought to be able to contribute to andsynergize with cell pathways which can eventually leadto Parkinson’s disease[5].PS-MNPs have also been found to penetrate bone mar-row via the circulatory system, causing hematologicaldefects, the effects of which depend on particle size, com-position, and individual response[4]. Smaller sized nano-particles are more hematoxic, and individual responsesare influenced by gut microbiota, cytokines, inflamma-tory response, and biochemical metabolites[4].References[1] C. Campanale, C. Massarelli, I. Savino, V. Loca-puto, and V. Uricchio. A detailed review study onpotential effects of microplastics and additives ofconcern on human health.International Journal ofEnvironmental Research and Public Health, 17(4),2020.[2] A. Guimarães, I. Charlie-Silva, and G. Malafaia.Toxic effects of naturally-aged microplastics on ze-brafish juveniles: A more realistic approach to plas-tic pollution in freshwater ecosystems.Journal ofHazardous Materials, 407:124833, 2021.[3] B. Jeong, J. Baek, J. Koo, S. Park, Y. Ryu, K. Kim,S. Zhang, C. Chung, R. Dogan, H. Choi, D. Um,T. Kim, W. Lee, J. Jeong, W. Shin, J. Lee, N. Kim,and D. Lee. Maternal exposure to polystyrenenanoplastics causes brain abnormalities in progeny.Journal of Hazardous Materials, 426:127815, 2022.[4] J. Jing, L. Zhang, L. Han, J. Wang, W. Zhang,Z. Liu, and A. Gao.Polystyrene micro-/nanoplastics induced hematopoietic damages viathe crosstalk of gut microbiota, metabolites, andcytokines.Environment International, 161:107131,2022.[5] B. Liang, Y. Huang, Y. Zhong, Z. Li, R. Ye,B. Wang, B. Zhang, H. Meng, X. Lin, J. Du,M. Hu, Q. Wu, H. Sui, X. Yang, and Z. Huang.Brain single-nucleus transcriptomics highlights thatpolystyrene nanoplastics potentially induce parkin-son’s disease-like neurodegeneration by causing en-ergy metabolism disorders in mice.Journal of Haz-ardous Materials, 430:128459, 2022.[6] X. Liu, Y. Zhao, J. Dou, Q. Hou, J. Cheng, andX. Jiang. Bioeffects of inhaled nanoplastics on neu-rons and alteration of animal behaviors through de-position in the brain.Nano Letters, 22(3):1091–1099, 2022. PMID: 35089039.[7] J. Prata, J. da Costa, I. Lopes, A. Duarte,and T. Rocha-Santos. Environmental exposureto microplastics: An overview on possible humanhealth effects.Science of The Total Environment,702:134455, 2020.[8] M. Prüst, J. Meijer, and R. Westerink. The plas-tic brain: neurotoxicity of micro- and nanoplastics.Particle and Fibre Toxicology, 17, 2020.[9] S. Shan, Y. Zhang, H. Zhao, T. Tao, andX. Zhao. Polystyrene nanoplastics penetrate acrossthe blood-brain barrier and induce activation ofmicroglia in the brain of mice.Chemosphere,298:134261, 2022.[10] P. Stapleton. Microplastic and nanoplastic trans-fer, accumulation, and toxicity in humans.CurrentOpinion in Toxicology, 28:62–69, 2021.[11] S. Wang, Q. Han, Z. Wei, Y. Wang, J. Xie, andM. Chen. Polystyrene microplastics affect learningand memory in mice by inducing oxidative stressand decreasing the level of acetylcholine.Food andChemical Toxicology, 162:112904, 2022.This document was created on March 31, 2022 and last updatedon April 1, 2022.[related_products section_heading="Related Products"]
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