Effects of Microplastic Exposure on Human Digestive, Reproductive, and Respiratory Health: A Rapid Systematic Review

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This article references 111 other publications.

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   Application of US EPA IRIS systematic review methods to the health effects of phthalates: Lessons learned and path forward

   Radke Elizabeth G; Yost Erin E; Roth Nicolas; Sathyanarayana Sheela; Whaley Paul

   Environment international (2020), 145 (), 105820 ISSN:.

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    Radke, E. G.; Glenn, B. S.; Braun, J. M.; Cooper, G. S. Phthalate exposure and female reproductive and developmental outcomes: a systematic review of the human epidemiological evidence. Environ. Int. 2019, 130, 104580  DOI: 10.1016/j.envint.2019.02.003

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    Phthalate exposure and female reproductive and developmental outcomes: a systematic review of the human epidemiological evidence

    Radke, Elizabeth G.; Glenn, Barbara S.; Braun, Joseph M.; Cooper, Glinda S.

    Environment International (2019), 130 (), 104580CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)

    A review. We performed a systematic review of the epidemiol. literature to identify the female reproductive and developmental effects assocd. with phthalate exposure. Six phthalates were included in the review: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), di-Bu phthalate (DBP), diisobutyl phthalate (DIBP), Bu benzyl phthalate (BBP), and di-Et phthalate (DEP). The initial literature search (of PubMed, Web of Science, and Toxline) included all studies of female reproductive and developmental effects in humans, and outcomes were selected for full systematic review based on data availability. For each outcome, studies were evaluated using criteria defined a priori for risk of bias and sensitivity by two reviewers using a domain-based approach. Evidence was synthesized by outcome and phthalate and strength of evidence was summarized using a structured framework. The primary outcomes reviewed here are (no. of included/excluded studies in parentheses): pubertal development (5/13), time to pregnancy (3/4), preterm birth (8/12), and spontaneous abortion (5/0). Among these outcomes, preterm birth had moderate evidence of a pos. assocn. with phthalate exposure (specifically DEHP, DBP, and DEP). Exposure levels for BBP, DIBP, and DINP were generally lower than for the phthalates with an obsd. effect, which may partially explain the difference due to lower sensitivity. Other phthalate/outcome combinations were considered to have slight or indeterminate evidence of an assocn. Overall, these results support that some phthalates may be assocd. with higher odds of preterm birth in humans, though there is some remaining inconsistency. More evidence is needed on the mechanism and relevant exposure window for this assocn.

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    Classification and Quantification of Microplastics (<100μm) Using a Focal Plane Array-Fourier Transform Infrared Imaging System and Machine Learning

    da Silva, Vitor H.; Murphy, Fionn; Amigo, Jose M.; Stedmon, Colin; Strand, Jakob

    Analytical Chemistry (Washington, DC, United States) (2020), 92 (20), 13724-13733CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)

    Microplastics are defined as microscopic plastic particles in the range from few micrometers and up to 5 mm. These small particles are classified as primary microplastics when they are manufd. in this size range, whereas secondary microplastics arise from the fragmentation of larger objects. Microplastics are widespread emerging pollutants, and studies are underway to det. potential harmfulness to biota and human health. However, progress is hindered by the lack of suitable anal. methods for rapid, routine, and unbiased measurements. This work aims to develop an automated anal. method for the characterization of small microplastics (<100μm) using micro-FTIR (μ-FTIR) hyperspectral imaging and machine learning tools. Partial least squares discriminant anal. (PLS-DA) and soft independent modeling of class analogy (SIMCA) models were evaluated, applying different data preprocessing strategies for classification of nine of the most common polymers produced worldwide. The hyperspectral images were also analyzed to quantify particle abundance and size automatically. PLS-DA presented a better anal. performance in comparison with SIMCA models with higher sensitivity, sensibility, and lower misclassification error. PLS-DA was less sensitive to edge effects on spectra and poorly focused regions of particles. The approach was tested on a seabed sediment sample (Roskilde Fjord, Denmark) to demonstrate the method efficiency. The proposed method offers an efficient automated approach for microplastic polymer characterization, abundance numeration, and size distribution with substantial benefits for method standardization.

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    Hartmann, N. B.; Hüffer, T.; Thompson, R. C.; Hassellöv, M.; Verschoor, A.; Daugaard, A. E.; Rist, S.; Karlsson, T.; Brennholt, N.; Cole, M.; Herrling, M. P.; Hess, M. C.; Ivleva, N. P.; Lusher, A. L.; Wagner, M. Are We Speaking the Same Language? Recommendations for a Definition and Categorization Framework for Plastic Debris. Environ. Sci. Technol. 2019, 53 (3), 1039– 1047,  DOI: 10.1021/acs.est.8b05297

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    Are We Speaking the Same Language? Recommendations for a Definition and Categorization Framework for Plastic Debris

    Hartmann, Nanna B.; Huffer, Thorsten; Thompson, Richard C.; Hassellov, Martin; Verschoor, Anja; Daugaard, Anders E.; Rist, Sinja; Karlsson, Therese; Brennholt, Nicole; Cole, Matthew; Herrling, Maria P.; Hess, Maren C.; Ivleva, Natalia P.; Lusher, Amy L.; Wagner, Martin

    Environmental Science & Technology (2019), 53 (3), 1039-1047CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)

    A review is given. The accumulation of plastic litter in natural environments is a global issue. Concerns over potential neg. impacts on the economy, wildlife, and human health provide strong incentives for improving the sustainable use of plastics. Despite the many voices raised on the issue, we lack a consensus on how to define and categorize plastic debris. This is evident for microplastics, where inconsistent size classes are used and where the materials to be included are under debate. While this is inherent in an emerging research field, an ambiguous terminol. results in confusion and miscommunication that may compromise progress in research and mitigation measures. Therefore, we need to be explicit on what exactly we consider plastic debris. Thus, we critically discuss the advantages and disadvantages of a unified terminol., propose a definition and categorization framework, and highlight areas of uncertainty. Going beyond size classes, our framework includes physicochem. properties (polymer compn., solid state, soly.) as defining criteria and size, shape, color, and origin as classifiers for categorization. Acknowledging the rapid evolution of our knowledge on plastic pollution, our framework will promote consensus building within the scientific and regulatory community based on a solid scientific foundation.

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    Browne, M. A.; Dissanayake, A.; Galloway, T. S.; Lowe, D. M.; Thompson, R. C. Ingested Microscopic Plastic Translocates to the Circulatory System of the Mussel, Mytilus edulis (L.). Environ. Sci. Technol. 2008, 42 (13), 5026– 5031,  DOI: 10.1021/es800249a

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    Ingested Microscopic Plastic Translocates to the Circulatory System of the Mussel, Mytilus edulis (L.)

    Browne, Mark A.; Dissanayake, Awantha; Galloway, Tamara S.; Lowe, David M.; Thompson, Richard C.

    Environmental Science & Technology (2008), 42 (13), 5026-5031CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)

    Plastics debris is accumulating in the environment and is fragmenting into smaller pieces; as it does, the potential for ingestion by animals increases. The consequences of macroplastic debris for wildlife are well documented, however the impacts of microplastic (<1 mm) are poorly understood. The mussel, Mytilus edulis, was used to investigate ingestion, translocation, and accumulation of this debris. Initial expts. showed that upon ingestion, microplastic accumulated in the gut. Mussels were subsequently exposed to treatments contg. seawater and microplastic (3.0 or 9.6 μm). After transfer to clean conditions, microplastic was tracked in the hemolymph. Particles translocated from the gut to the circulatory system within 3 days and persisted for over 48 days. Abundance of microplastic was greatest after 12 days and declined thereafter. Smaller particles were more abundant than larger particles and our data indicate as plastic fragments into smaller particles, the potential for accumulation in the tissues of an organism increases. The short-term pulse exposure used here did not result in significant biol. effects. However, plastics are exceedingly durable and so further work using a wider range of organisms, polymers, and periods of exposure will be required to establish the biol. consequences of this debris.

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    Waller, C. L.; Griffiths, H. J.; Waluda, C. M.; Thorpe, S. E.; Loaiza, I.; Moreno, B.; Pacherres, C. O.; Hughes, K. A. Microplastics in the Antarctic marine system: An emerging area of research. Science of The Total Environment 2017, 598, 220– 227,  DOI: 10.1016/j.scitotenv.2017.03.283

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    Jamieson, A. J.; Brooks, L. S. R.; Reid, W. D. K.; Piertney, S. B.; Narayanaswamy, B. E.; Linley, T. D. Microplastics and synthetic particles ingested by deep-sea amphipods in six of the deepest marine ecosystems on Earth. R Soc. open sci. 2019, 6 (2), 180667  DOI: 10.1098/rsos.180667

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    Microplastics and synthetic particles ingested by deep-sea amphipods in six of the deepest marine ecosystems on Earth

    Jamieson, A. J.; Brooks, L. S. R.; Reid, W. D. K.; Piertney, S. B.; Narayanaswamy, B. E.; Linley, T. D.

    Royal Society Open Science (2019), 6 (2), 180667CODEN: RSOSAV; ISSN:2054-5703. (Royal Society)

    While there is now an established recognition of microplastic pollution in the oceans, and the detrimental effects this may have on marine animals, the ocean depth at which such contamination is ingested by organisms has still not been established. Here, we detect the presence of ingested microplastics in the hindguts of Lysianassoidea amphipod populations, in six deep ocean trenches from around the Pacific Rim (Japan, Izu-Bonin, Mariana, Kermadec, New Hebrides and the Peru-Chile trenches), at depths ranging from 7000 m to 10 890 m. This illustrates that microplastic contaminants occur in the very deepest reaches of the oceans. Over 72% of individuals examd. (65 of 90) contained at least one microparticle. The no. of microparticles ingested per individual across all trenches ranged from 1 to 8. The mean and std. error of microparticles varied per trench, from 0.9±0.4 (New Hebrides Trench) to 3.3±0.7 (Mariana Trench). A subsample of microfibres and fragments analyzed using FTIR were found to be a collection of plastic and synthetic materials (Nylon, polyethylene, polyamide, polyvinyl alc., polyvinylchloride, often with inorg. filler material), semi-synthetic (rayon and lyocell) and natural fiber (ramie). Notwithstanding, this study reports the deepest record of microplastic ingestion, indicating that anthropogenic debris is bioavailable to organisms at some of the deepest locations in the Earth's oceans.

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    Peeken, I.; Primpke, S.; Beyer, B.; Gütermann, J.; Katlein, C.; Krumpen, T.; Bergmann, M.; Hehemann, L.; Gerdts, G. Arctic sea ice is an important temporal sink and means of transport for microplastic. Nat. Commun. 2018, 9 (1), 1505,  DOI: 10.1038/s41467-018-03825-5

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    Arctic sea ice is an important temporal sink and means of transport for microplastic

    Peeken Ilka; Primpke Sebastian; Beyer Birte; Gutermann Julia; Katlein Christian; Krumpen Thomas; Bergmann Melanie; Hehemann Laura; Gerdts Gunnar

    Nature communications (2018), 9 (1), 1505 ISSN:.

    Microplastics (MP) are recognized as a growing environmental hazard and have been identified as far as the remote Polar Regions, with particularly high concentrations of microplastics in sea ice. Little is known regarding the horizontal variability of MP within sea ice and how the underlying water body affects MP composition during sea ice growth. Here we show that sea ice MP has no uniform polymer composition and that, depending on the growth region and drift paths of the sea ice, unique MP patterns can be observed in different sea ice horizons. Thus even in remote regions such as the Arctic Ocean, certain MP indicate the presence of localized sources. Increasing exploitation of Arctic resources will likely lead to a higher MP load in the Arctic sea ice and will enhance the release of MP in the areas of strong seasonal sea ice melt and the outflow gateways.

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    Kannan, K.; Vimalkumar, K. A Review of Human Exposure to Microplastics and Insights Into Microplastics as Obesogens. Front. Endocrinol. 2021, 12, 724989,  DOI: 10.3389/fendo.2021.724989

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    A Review of Human Exposure to Microplastics and Insights Into Microplastics as Obesogens

    Kannan Kurunthachalam; Vimalkumar Krishnamoorthi

    Frontiers in endocrinology (2021), 12 (), 724989 ISSN:1664-2392.

    The ubiquitous exposure of humans to microplastics (MPs) through inhalation of particles in air and ingestion in dust, water, and diet is well established. Humans are estimated to ingest tens of thousands to millions of MP particles annually, or on the order of several milligrams daily. Available information suggests that inhalation of indoor air and ingestion of drinking water bottled in plastic are the major sources of MP exposure. Little is known on the occurrence of MPs in human diet. Evidence is accumulating that feeding bottles and medical devices can contribute to MP exposure in newborns and infants. Biomonitoring studies of human stool, fetus, and placenta provide direct evidence of MP exposure in infants and children. MPs <20 μm were reported to cross biological membranes. Although plastics were once perceived as inert materials, MP exposure in laboratory animals is linked to various forms of inflammation, immunological response, endocrine disruption, alteration of lipid and energy metabolism, and other disorders. Whereas exposure to MPs itself is a concern, MPs can also be sources of exposure to plastic additives and other toxicants. Exposure of human cell lines to MP additives such as phthalates, bisphenols, and organotins causes adverse effects through the activation of nuclear receptors, peroxisome proliferator-activated receptors (PPARs) α, β, and γ, and retinoid X receptor (RXR), leading to oxidative stress, cytotoxicity, immunotoxicity, thyroid hormone disruption, and altered adipogenesis and energy production. The size, shape, chemical composition, surface charge, and hydrophobicity of MPs influence their toxicity. Maternal transfer of MPs to the developing fetus has been demonstrated in exposed laboratory animals and through the analysis of human placenta. In laboratory animal studies, maternal exposure to MPs altered energy and lipid metabolism in offspring and subsequent generations. Moreover, concomitant with the global increase in plastics production, the prevalence of overweight and obesity in human populations has increased over the past five decades, and there is evidence to support the hypothesis that MPs and their additives are potential obesogens. Even though MP exposures are ubiquitous and toxic effects from such exposures are a concern, systematic studies on this topic remain urgently needed.

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    Ragusa, A.; Svelato, A.; Santacroce, C.; Catalano, P.; Notarstefano, V.; Carnevali, O.; Papa, F.; Rongioletti, M. C. A.; Baiocco, F.; Draghi, S.; D’Amore, E.; Rinaldo, D.; Matta, M.; Giorgini, E. Plasticenta: First evidence of microplastics in human placenta. Environ. Int. 2021, 146, 106274  DOI: 10.1016/j.envint.2020.106274

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    Plasticenta: First evidence of microplastics in human placenta

    Ragusa, Antonio; Svelato, Alessandro; Santacroce, Criselda; Catalano, Piera; Notarstefano, Valentina; Carnevali, Oliana; Papa, Fabrizio; Rongioletti, Mauro Ciro Antonio; Baiocco, Federico; Draghi, Simonetta; D'Amore, Elisabetta; Rinaldo, Denise; Matta, Maria; Giorgini, Elisabetta

    Environment International (2021), 146 (), 106274CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)

    Microplastics are particles smaller than five millimeters deriving from the degrdn. of plastic objects present in the environment. Microplastics can move from the environment to living organisms, including mammals. In this study, six human placentas, collected from consenting women with physiol. pregnancies, were analyzed by Raman Microspectroscopy to evaluate the presence of microplastics. In total, 12 microplastic fragments (ranging from 5 to 10 μm in size), with spheric or irregular shape were found in 4 placentas (5 in the fetal side, 4 in the maternal side and 3 in the chorioamniotic membranes); all microplastics particles were characterized in terms of morphol. and chem. compn. All of them were pigmented; three were identified as stained polypropylene a thermoplastic polymer, while for the other nine it was possible to identify only the pigments, which were all used for man-made coatings, paints, adhesives, plasters, finger paints, polymers and cosmetics and personal care products.

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    Ragusa, A.; Notarstefano, V.; Svelato, A.; Belloni, A.; Gioacchini, G.; Blondeel, C.; Zucchelli, E.; De Luca, C.; D’Avino, S.; Gulotta, A.; Carnevali, O.; Giorgini, E. Raman Microspectroscopy Detection and Characterisation of Microplastics in Human Breastmilk. Polymers 2022, 14 (13), 2700,  DOI: 10.3390/polym14132700

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    Raman Microspectroscopy Detection and Characterisation of Microplastics in Human Breastmilk

    Ragusa, Antonio; Notarstefano, Valentina; Svelato, Alessandro; Belloni, Alessia; Gioacchini, Giorgia; Blondeel, Christine; Zucchelli, Emma; De Luca, Caterina; D'Avino, Sara; Gulotta, Alessandra; Carnevali, Oliana; Giorgini, Elisabetta

    Polymers (Basel, Switzerland) (2022), 14 (13), 2700CODEN: POLYCK; ISSN:2073-4360. (MDPI AG)

    The widespread use of plastics dets. the inevitable human exposure to its byproducts, including microplastics (MPs), which enter the human organism mainly by ingestion, inhalation, and dermal contact. Once internalised, MPs may pass across cell membranes and translocate to different body sites, triggering specific cellular mechanisms. Hence, the potential health impairment caused by the internalisation and accumulation of MPs is of prime concern, as confirmed by numerous studies reporting evident toxic effects in various animal models, marine organisms, and human cell lines. In this pilot single-center observational prospective study, human breastmilk samples collected from N. 34 women were analyzed by Raman Microspectroscopy, and, for the first time, MP contamination was found in 26 out of 34 samples. The detected microparticles were classified according to their shape, color, dimensions, and chem. compn. The most abundant MPs were composed of polyethylene, polyvinyl chloride, and polypropylene, with sizes ranging from 2 to 12μm. MP data were statistically analyzed in relation to specific patients' data (age, use of personal care products contg. plastic compds., and consumption of fish/shellfish, beverages, and food in plastic packaging), but no significant relationship was found, suggesting that the ubiquitous MP presence makes human exposure inevitable.

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    Horvatits, T.; Tamminga, M.; Liu, B.; Sebode, M.; Carambia, A.; Fischer, L.; Puschel, K.; Huber, S.; Fischer, E. K. Microplastics detected in cirrhotic liver tissue. EBioMedicine 2022, 82, 104147  DOI: 10.1016/j.ebiom.2022.104147

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    Microplastics detected in cirrhotic liver tissue

    Horvatits, Thomas; Tamminga, Matthias; Liu, Beibei; Sebode, Marcial; Carambia, Antonella; Fischer, Lutz; Pueschel, Klaus; Huber, Samuel; Fischer, Elke Kerstin

    EBioMedicine (2022), 82 (), 104147CODEN: EBIOAX; ISSN:2352-3964. (Elsevier B.V.)

    The contamination of ecosystem compartments by microplastics (MPs) is an ubiquitous problem. MPs have been obsd. in mice tissues, and recently in human blood, stool and placenta. However, two aspects remain unclear: whether MPs accumulate in peripheral organs, specifically in the liver, and if liver cirrhosis favors this process. We aimed to examine human liver tissue samples to det. whether MPs accumulate in the liver. This proof-of-concept case series, conducted in Germany, Europe, analyzed tissue samples of 6 patients with liver cirrhosis and 5 individuals without underlying liver disease. A total of 17 samples (11 liver, 3 kidney and 3 spleen samples) were analyzed according to the final protocol. A reliable method for detection of MP particles from 4 to 30μm in human tissue was developed. Chem. digestion of tissue samples, staining with Nile red, subsequent fluorescent microscopy and Raman spectroscopy were performed. Morphol., size and compn. of MP polymers were assessed. Considering the limit of detection, all liver, kidney and spleen samples from patients without underlying liver disease tested neg. for MPs. In contrast, MP concns. in cirrhotic liver tissues tested pos. and showed significantly higher concns. compared to liver samples of individuals without underlying liver disease. Six different microplastic polymers ranging from 4 to 30μm in size were detected. This proof-of-concept case series assessed the presence of MPs in human liver tissue and found six different MP polymers in the liver of individuals with liver cirrhosis, but not in those without underlying liver disease. Future studies are needed to evaluate whether hepatic MP accumulation represents a potential cause in the pathogenesis of fibrosis, or a consequence of cirrhosis and portal hypertension. No funding was received for conducting this investigator driven study.

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    Senathirajah, K.; Attwood, S.; Bhagwat, G.; Carbery, M.; Wilson, S.; Palanisami, T. Estimation of the mass of microplastics ingested – A pivotal first step towards human health risk assessment. Journal of Hazardous Materials 2021, 404, 124004  DOI: 10.1016/j.jhazmat.2020.124004

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    Estimation of mass of microplastics ingested - A pivotal first step towards human health risk assessment

    Senathirajah, Kala; Attwood, Simon; Bhagwat, Geetika; Carbery, Maddison; Wilson, Scott; Palanisami, Thava

    Journal of Hazardous Materials (2021), 404 (Part_B), 124004CODEN: JHMAD9; ISSN:0304-3894. (Elsevier B.V.)

    The ubiquitous presence of microplastics in the food web has been established. However, the mass of microplastics exposure to humans is not defined, impeding the human health risk assessment. Our objectives were to ext. the data from the available evidence on the no. and mass of microplastics from various sources, to det. the uncertainties in the existing data, to set future research directions, and derive a global av. rate of microplastic ingestion to assist in the development of human health risk assessments and effective management and policy options. To enable the comparison of microplastics exposure across a range of sources, data extn. and standardization was coupled with the adoption of conservative assumptions. Following the anal. of data from fifty-nine publications, an av. mass for individual microplastics in the 0-1 mm size range was calcd. Subsequently, we estd. that globally on av., humans may ingest 0.1-5 g of microplastics weekly through various exposure pathways. This was the first attempt to transform microplastic counts into a mass value relevant to human toxicol. The detn. of an ingestion rate is fundamental to assess the human health risks of microplastic ingestion. These findings will contribute to future human health risk assessment frameworks.

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    Plastic ingestion by people could be equating to a credit card a week. Featured News/Newsroom/The University of Newcastle, Australia. https://www.newcastle.edu.au/newsroom/featured/plastic-ingestion-by-people-could-be-equating-to-a-credit-card-a-week (accessed 2024-08-09).

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    Seeley, M. E.; Hale, R. C.; Zwollo, P.; Vogelbein, W.; Verry, G.; Wargo, A. R. Microplastics exacerbate virus-mediated mortality in fish. Science of The Total Environment 2023, 866, 161191  DOI: 10.1016/j.scitotenv.2022.161191

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    Charlton-Howard, H. S.; Bond, A. L.; Rivers-Auty, J.; Lavers, J. L. Plasticosis”: Characterising macro- and microplastic-associated fibrosis in seabird tissues. J. Hazard Mater. 2023, 450, 131090  DOI: 10.1016/j.jhazmat.2023.131090

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    Ageel, H. K.; Harrad, S.; Abdallah, M. A. E. Occurrence, human exposure, and risk of microplastics in the indoor environment. Environmental Science: Processes & Impacts 2022, 24 (1), 17– 31,  DOI: 10.1039/D1EM00301A

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    Cho, Y. M.; Choi, K. H. The current status of studies of human exposure assessment of microplastics and their health effects: a rapid systematic review. Environ. Anal Health Toxicol 2021, 36 (1), e2021004– 0,  DOI: 10.5620/eaht.2021004

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    Campanale, C.; Massarelli, C.; Savino, I.; Locaputo, V.; Uricchio, V. F. A Detailed Review Study on Potential Effects of Microplastics and Additives of Concern on Human Health. Int. J. Environ. Res. Public Health 2020, 17 (4), 1212,  DOI: 10.3390/ijerph17041212

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    A detailed review study on potential effects of microplastics and additives of concern on human health

    Campanale, Claudia; Massarelli, Carmine; Savino, Ilaria; Locaputo, Vito; Uricchio, Vito Felice

    International Journal of Environmental Research and Public Health (2020), 17 (4), 1212CODEN: IJERGQ; ISSN:1660-4601. (MDPI AG)

    A review. The distribution and abundance of microplastics into the world are so extensive that many scientists use them as key indicators of the recent and contemporary period defining a new historical epoch: The Plasticene. However, the implications of microplastics are not yet thoroughly understood. There is considerable complexity involved to understand their impact due to different phys.-chem. properties that make microplastics multifaceted stressors. If, on the one hand, microplastics carry toxic chems. in the ecosystems, thus serving as vectors of transport, they are themselves, on the other hand, a cocktail of hazardous chems. that are added voluntarily during their prodn. as additives to increase polymer properties and prolong their life. To date, there is a considerable lack of knowledge on the major additives of concern that are used in the plastic industry, on their fate once microplastics dispose into the environment, and on their consequent effects on human health when assocd. with micro and nanoplastics. The present study emphasizes the most toxic and dangerous chem. substances that are contained in all plastic products to describe the effects and implications of these hazardous chems. on human health, providing a detailed overview of studies that have investigated their abundance on microplastics. In the present work, we conducted a capillary review of the literature on micro and nanoplastic exposure pathways and their potential risk to human health to summarize current knowledge with the intention of better focus future research in this area and fill knowledge gaps.

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    Rahman, A.; Sarkar, A.; Yadav, O. P.; Achari, G.; Slobodnik, J. Potential human health risks due to environmental exposure to nano- and microplastics and knowledge gaps: A scoping review. Science of The Total Environment 2021, 757, 143872  DOI: 10.1016/j.scitotenv.2020.143872

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    Potential human health risks due to environmental exposure to nano- and microplastics and knowledge gaps: A scoping review

    Rahman, Arifur; Sarkar, Atanu; Yadav, Om Prakash; Achari, Gopal; Slobodnik, Jaroslav

    Science of the Total Environment (2021), 757 (), 143872CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)

    A review. Microplastics are an emerging global environmental contaminant that are affecting multiple spheres. Despite their ubiquity in all spheres of life and ecol., little is known about the health effects of microplastics exposure to humans. This scoping review explores the existing evidence on the potential human health effects of microplastics and subsequent knowledge gaps. An electronic search of published articles in PubMed, Scopus, EMBASE, Cochrane databases, and Google Scholar was conducted using a combination of subject headings and keywords relating to microplastics and human health effects. The initial search resulted in 17,043 published articles and gray literature documents. After a full review of published articles and their refs., 129 publications were identified for further detailed review. These articles indicate that human exposure to microplastics can occur through ingestion, inhalation, and dermal contact due to their presence in food, water, air, and consumer products. Microplastics exposure can cause toxicity through oxidative stress, inflammatory lesions, and increased uptake or translocation. Several studies have demonstrated the potentiality of metabolic disturbances, neurotoxicity, and increased cancer risk in humans. Moreover, microplastics have been found to release their constituent compds. as well as those that are adsorbed onto their surface. Further research is needed to quantify the effects of microplastics on human health and their pathogenesis.

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    Batool, I.; Qadir, A.; Levermore, J. M.; Kelly, F. J. Dynamics of airborne microplastics, appraisal and distributional behaviour in atmosphere; a review. Science of The Total Environment 2022, 806, 150745  DOI: 10.1016/j.scitotenv.2021.150745

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    Marfella, R.; Prattichizzo, F.; Sardu, C.; Fulgenzi, G.; Graciotti, L.; Spadoni, T.; D’Onofrio, N.; Scisciola, L.; La Grotta, R.; Frigé, C.; Pellegrini, V.; Municinò, M.; Siniscalchi, M.; Spinetti, F.; Vigliotti, G.; Vecchione, C.; Carrizzo, A.; Accarino, G.; Squillante, A. Microplastics and Nanoplastics in Atheromas and Cardiovascular Events. N. Engl. J. Med. 2024, 390 (10), 900– 910,  DOI: 10.1056/NEJMoa2309822

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    Amereh, F.; Amjadi, N.; Mohseni-Bandpei, A.; Isazadeh, S.; Mehrabi, Y.; Eslami, A.; Naeiji, Z.; Rafiee, M. Placental plastics in young women from general population correlate with reduced foetal growth in IUGR pregnancies. Environmental Pollution (Barking, Essex: 1987) 2022, 314, 120174  DOI: 10.1016/j.envpol.2022.120174

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    Xue, J.; Xu, Z.; Hu, X.; Lu, Y.; Zhao, Y.; Zhang, H. Microplastics in maternal amniotic fluid and their associations with gestational age. Sci. Total Environ. 2024, 920, 171044  DOI: 10.1016/j.scitotenv.2024.171044

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    Xu, J. L.; Lin, X.; Wang, J. J.; Gowen, A. A. A review of potential human health impacts of micro- and nanoplastics exposure. Sci. Total Environ. 2022, 851, 158111  DOI: 10.1016/j.scitotenv.2022.158111

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    A review of potential human health impacts of micro- and nanoplastics exposure

    Xu, Jun-Li; Lin, Xiaohui; Wang, Jing Jing; Gowen, Aoife A.

    Science of the Total Environment (2022), 851 (Part_1), 158111CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)

    A review. This systematic review aims to summarize the current knowledge on biol. effects of micro- and nanoplastics (MNPs) on human health based on mammalian systems. An extensive search of the literature led to a total of 133 primary research articles on the health relevance of MNPs. Our findings revealed that although the study of MNP cytotoxicity and inflammatory response represents a major research theme, most studies (105 articles) focused on the effects of polystyrene MNPs due to their wide availability as a well characterised research material that can be manufd. with a large range of particle sizes, fluorescence labeling as well as various surface modifications. Among the 133 studies covered in this review, 117 articles reported adverse health effects after being exposed to MNPs. Mammalian in vitro studies identified multiple biol. effects including cytotoxicity, oxidative stress, inflammatory response, genotoxicity, embryotoxicity, hepatotoxicity, neurotoxicity, renal toxicity and even carcinogenicity, while rodent in vivo models confirmed the bioaccumulation of MNPs in the liver, spleen, kidney, brain, lung and gut, presenting adverse effects at different levels including reproductive toxic effects and trans-generational toxicity. In contrast, the remaining 16 studies indicated an insignificant impact of MNPs on humans. A few studies attempted to investigate the mechanisms or factors driving the toxicity of MNPs and identified several detg. factors including size, concn., shape, surface charge, attached pollutants and weathering process, which, however, were not benchmarked or considered by most studies. This review demonstrates that there are still many inconsistencies in the evaluation of the potential health effects of MNPs due to the lack of comparability between studies. Current limitations hindering the attainment of reproducible conclusions as well as recommendations for future research directions are also presented.

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    Garritty, C.; Gartlehner, G.; Nussbaumer-Streit, B.; King, V. J.; Hamel, C.; Kamel, C.; Affengruber, L.; Stevens, A. Cochrane Rapid Reviews Methods Group offers evidence-informed guidance to conduct rapid reviews. Journal of Clinical Epidemiology 2021, 130, 13– 22,  DOI: 10.1016/j.jclinepi.2020.10.007

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    Woodruff, T. J.; Sutton, P. The navigation guide systematic review methodology: a rigorous and transparent method for translating environmental health science into better health outcomes. Environ. Health Perspect. 2014, 122 (10), 1007– 1014,  DOI: 10.1289/ehp.1307175

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    The Navigation Guide systematic review methodology: a rigorous and transparent method for translating environmental health science into better health outcomes

    Woodruff Tracey J; Sutton Patrice

    Environmental health perspectives (2014), 122 (10), 1007-14 ISSN:.

    BACKGROUND: Synthesizing what is known about the environmental drivers of health is instrumental to taking prevention-oriented action. Methods of research synthesis commonly used in environmental health lag behind systematic review methods developed in the clinical sciences over the past 20 years. OBJECTIVES: We sought to develop a proof of concept of the "Navigation Guide," a systematic and transparent method of research synthesis in environmental health. DISCUSSION: The Navigation Guide methodology builds on best practices in research synthesis in evidence-based medicine and environmental health. Key points of departure from current methods of expert-based narrative review prevalent in environmental health include a prespecified protocol, standardized and transparent documentation including expert judgment, a comprehensive search strategy, assessment of "risk of bias," and separation of the science from values and preferences. Key points of departure from evidence-based medicine include assigning a "moderate" quality rating to human observational studies and combining diverse evidence streams. CONCLUSIONS: The Navigation Guide methodology is a systematic and rigorous approach to research synthesis that has been developed to reduce bias and maximize transparency in the evaluation of environmental health information. Although novel aspects of the method will require further development and validation, our findings demonstrated that improved methods of research synthesis under development at the National Toxicology Program and under consideration by the U.S. Environmental Protection Agency are fully achievable. The institutionalization of robust methods of systematic and transparent review would provide a concrete mechanism for linking science to timely action to prevent harm.

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    Johnson, P. I.; Koustas, E.; Vesterinen, H. M.; Sutton, P.; Atchley, D. S.; Kim, A. N.; Campbell, M.; Donald, J. M.; Sen, S.; Bero, L.; Zeise, L.; Woodruff, T. J. Application of the Navigation Guide systematic review methodology to the evidence for developmental and reproductive toxicity of triclosan. Environ. Int. 2016, 92–93, 716– 728,  DOI: 10.1016/j.envint.2016.03.009

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    Application of the Navigation Guide systematic review methodology to the evidence for developmental and reproductive toxicity of triclosan

    Johnson, Paula I.; Koustas, Erica; Vesterinen, Hanna M.; Sutton, Patrice; Atchley, Dylan S.; Kim, Allegra N.; Campbell, Marlissa; Donald, James M.; Sen, Saunak; Bero, Lisa; Zeise, Lauren; Woodruff, Tracey J.

    Environment International (2016), 92-93 (), 716-728CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)

    There are reports of developmental and reproductive health effects assocd. with the widely used biocide triclosan. Apply the Navigation Guide systematic review methodol. to answer the question: Does exposure to triclosan have adverse effects on human development or reprodn. We applied the first 3 steps of the Navigation Guide methodol.: (1) Specify a study question, (2) Select the evidence, and (3) Rate quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using pre-specified criteria. We assessed the no. and type of all relevant studies. We evaluated each included study for risk of bias and rated the quality and strength of the evidence for the selected outcomes. We conducted a meta-anal. on a subset of suitable data. We found 4282 potentially relevant records, and 81 records met our inclusion criteria. Of the more than 100 endpoints identified by our search, we focused our evaluation on hormone concn. outcomes, which had the largest human and non-human mammalian data set. Three human studies and 8 studies conducted in rats reported thyroxine levels as outcomes. The rat data were amenable to meta-anal. Because only one of the human thyroxine studies quantified exposure, we did not conduct a meta-anal. of the human data. Through meta-anal. of the data for rats, we estd. for prenatal exposure a 0.09% (95% CI: - 0.20, 0.02) redn. in thyroxine concn. per mg triclosan/kg-bw in fetal and young rats compared to control. For postnatal exposure we estd. a 0.31% (95% CI: - 0.38, - 0.23) redn. in thyroxine per mg triclosan/kg-bw, also compared to control. Overall, we found low to moderate risk of bias across the human studies and moderate to high risk of bias across the non-human studies, and assigned a "moderate/low" quality rating to the body of evidence for human thyroid hormone alterations and a "moderate" quality rating to the body of evidence for non-human thyroid hormone alterations. Based on this application of the Navigation Guide systematic review methodol., we concluded that there was "sufficient" non-human evidence and "inadequate" human evidence of an assocn. between triclosan exposure and thyroxine concns., and consequently, triclosan is "possibly toxic" to reproductive and developmental health. Thyroid hormone disruption is an upstream indicator of developmental toxicity. Addnl. endpoints may be identified as being of equal or greater concern as other data are developed or evaluated.

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    Johnson, P. I.; Sutton, P.; Atchley, D. S.; Koustas, E.; Lam, J.; Sen, S.; Robinson, K. A.; Axelrad, D. A.; Woodruff, T. J. The Navigation Guide─Evidence-based medicine meets environmental health: Systematic review of human evidence for PFOA effects on fetal growth. Environ. Health Perspect. 2014, 122, 1028,  DOI: 10.1289/ehp.1307893

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    The Navigation Guide - evidence-based medicine meets environmental health: systematic review of human evidence for PFOA effects on fetal growth

    Johnson Paula I; Sutton Patrice; Atchley Dylan S; Koustas Erica; Lam Juleen; Sen Saunak; Robinson Karen A; Axelrad Daniel A; Woodruff Tracey J

    Environmental health perspectives (2014), 122 (10), 1028-39 ISSN:.

    BACKGROUND: The Navigation Guide methodology was developed to meet the need for a robust method of systematic and transparent research synthesis in environmental health science. We conducted a case study systematic review to support proof of concept of the method. OBJECTIVE: We applied the Navigation Guide systematic review methodology to determine whether developmental exposure to perfluorooctanoic acid (PFOA) affects fetal growth in humans. METHODS: We applied the first 3 steps of the Navigation Guide methodology to human epidemiological data: 1) specify the study question, 2) select the evidence, and 3) rate the quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using prespecified criteria. We evaluated each study for risk of bias and conducted meta-analyses on a subset of studies. We rated quality and strength of the entire body of human evidence. RESULTS: We identified 18 human studies that met our inclusion criteria, and 9 of these were combined through meta-analysis. Through meta-analysis, we estimated that a 1-ng/mL increase in serum or plasma PFOA was associated with a -18.9 g (95% CI: -29.8, -7.9) difference in birth weight. We concluded that the risk of bias across studies was low, and we assigned a "moderate" quality rating to the overall body of human evidence. CONCLUSION: On the basis of this first application of the Navigation Guide systematic review methodology, we concluded that there is "sufficient" human evidence that developmental exposure to PFOA reduces fetal growth.

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    Lam, J.; Koustas, E.; Sutton, P.; Johnson, P. I.; Atchley, D. S.; Sen, S.; Robinson, K. A.; Axelrad, D. A.; Woodruff, T. J. The Navigation Guide─Evidence-based medicine meets environmental health: Integration of animal and human evidence for PFOA effects on fetal growth. Environ. Health Perspect 2014, 122 (10), 1040– 1051,  DOI: 10.1289/ehp.1307923

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    Toxicity Testing in the 21st Century: A Vision and a Strategy

    Krewski, Daniel; Acosta, Daniel, Jr.; Andersen, Melvin; Anderson, Henry; Bailar, John C., III; Boekelheide, Kim; Brent, Robert; Charnley, Gail; Cheung, Vivian G.; Green, Sidney, Jr.; Kelsey, Karl T.; Kerkvliet, Nancy I.; Li, Abby A.; McCray, Lawrence; Meyer, Otto; Patterson, Reid D.; Pennie, William; Scala, Robert A.; Solomon, Gina M.; Stephens, Martin; Yager, James; Zeise, Lauren

    Journal of Toxicology and Environmental Health, Part B: Critical Reviews (2010), 13 (2-4), 51-138CODEN: JTECFR; ISSN:1093-7404. (Taylor & Francis, Inc.)

    A review. With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, pptd. a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qual. endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quant. parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biol. models would be implemented to det. the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concns. would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results and would cover several test agents, compared to traditional toxicol. testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biol. models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biol.

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    Lind, L.; Araujo, J. A.; Barchowsky, A.; Belcher, S.; Berridge, B. R.; Chiamvimonvat, N.; Chiu, W. A.; Cogliano, V. J.; Elmore, S.; Farraj, A. K.; Gomes, A. V.; McHale, C. M.; Meyer-Tamaki, K. B.; Posnack, N. G.; Vargas, H. M.; Yang, X.; Zeise, L.; Zhou, C.; Smith, M. T. Key Characteristics of Cardiovascular Toxicants. Environ. Health Perspect. 2021, 129 (9), 095001  DOI: 10.1289/EHP9321

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    Luderer, U.; Eskenazi, B.; Hauser, R.; Korach, K. S.; McHale, C. M.; Moran, F.; Rieswijk, L.; Solomon, G.; Udagawa, O.; Zhang, L.; Zlatnik, M.; Zeise, L.; Smith, M. T. Proposed key characteristics of female reproductive toxicants as an approach for organizing and evaluating mechanistic data in hazard assessment. Environ. Health Perspect. 2019, 127 (7), 75001,  DOI: 10.1289/EHP4971

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    Rusyn, I.; Arzuaga, X.; Cattley, R. C.; Corton, J. C.; Ferguson, S. S.; Godoy, P.; Guyton, K. Z.; Kaplowitz, N.; Khetani, S. R.; Roberts, R. A.; Roth, R. A.; Smith, M. T. Key characteristics of human hepatotoxicants as a basis for identification and characterization of the causes of liver toxicity. Hepatology 2021, 74, 3486,  DOI: 10.1002/hep.31999

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    Vesterinen, H. M.; Morello-Frosch, R.; Sen, S.; Zeise, L.; Woodruff, T. J. Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence. PLoS One 2017, 12 (7), e0176331,  DOI: 10.1371/journal.pone.0176331

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    Vesterinen, H. M.; Johnson, P. I.; Atchley, D. S.; Sutton, P.; Lam, J.; Zlatnik, M. G.; Sen, S.; Woodruff, T. J. Fetal growth and maternal glomerular filtration rate: A systematic review. J. Matern Fetal Neonatal Med. 2015, 28 (18), 2176– 2181,  DOI: 10.3109/14767058.2014.980809

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    Fetal growth and maternal glomerular filtration rate: a systematic review

    Vesterinen Hanna M; Johnson Paula I; Atchley Dylan S; Sutton Patrice; Woodruff Tracey J; Johnson Paula I; Lam Juleen; Zlatnik Marya G; Sen Saunak

    The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians (2015), 28 (18), 2176-81 ISSN:.

    OBJECTIVE: Glomerular filtration rate (GFR) may influence concentrations of biomarkers of exposure and their etiologic significance in observational studies of associations between environmental contaminants and fetal growth. It is unknown whether the size of a developing fetus affects maternal GFR such that a small fetus leads to reduced plasma volume expansion (PVE), reduced GFR and subsequent higher concentrations of biomarkers in maternal serum. Our objective was to answer the question: "Is there an association between fetal growth and maternal GFR in humans?" METHODS: We adapted and applied the Navigation Guide systematic review methodology to assess the evidence of an association between fetal growth and GFR, either directly or indirectly via reduction in PVE. RESULTS: We identified 35 relevant studies. We rated 31 human and two non-human observational studies as "low" quality and two experimental non-human studies as "very low" quality. We rated all three evidence streams as "inadequate". The association between fetal growth and GFR was "not classifiable" according to pre-specified definitions. CONCLUSIONS: There is currently insufficient evidence to support the plausibility of a reverse causality hypothesis for associations between exposure to environmental chemicals during pregnancy and fetal growth. Further research would be needed to confirm or disprove this hypothesis.

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60. 60

    Higgins, J.P.T.; Thomas, J.; Chandler, J.; Cumpston, M.; Li, T.; Page, M.J.; Welch, V.A., editors. Cochrane Handbook for Systematic Reviews of Interventions version 6.5 (updated August 2024). Chapter 12. Cochrane: 2024; available from www.training.cochrane.org/handbook.

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    Brown, L. D.; Cai, T. T.; DasGupta, A. Interval Estimation for a Binomial Proportion. Statistical Science 2001, 16 (2), 101– 117,  DOI: 10.1214/ss/1009213286

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    Amrhein, V.; Greenland, S.; McShane, B. Scientists rise up against statistical significance. Nature. 2019, 567, 305– 307,  DOI: 10.1038/d41586-019-00857-9

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    Scientists rise up against statistical significance

    Amrhein, Valentin; Greenland, Sander; McShane, Blake

    Nature (London, United Kingdom) (2019), 567 (7748), 305-307CODEN: NATUAS; ISSN:0028-0836. (Nature Research)

    Valentin Amrhein, Sander Greenland, Blake McShane and more than 800 signatories call for an end to hyped claims and the dismissal of possibly crucial effects.

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63. 63

    Higgins, J., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M., Welch, V., Eds. Chapter 9: Summarizing study characteristics and preparing for synthesis. In Cochrane Handbook for Systematic Reviews of Interventions version 6.5; https://training.cochrane.org/handbook/current/chapter-09 (retrieved 2024-09-30).

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    National Toxicology Program. Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration; U.S. Department of Health and Human Services, 2019; pp 29– 32. https://ntp.niehs.nih.gov/ntp/ohat/pubs/handbookmarch2019_508.pdf (accessed 2023-02-10).

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65. 65

    California Office of Environmental Health Hazard Assessment. About proposition 65. 2021. https://oehha.ca.gov/proposition-65/about-proposition-65 (accessed 2022-08-10).

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66. 66

    U.S. Environmental Protection Agency. Guidelines for Reproductive Toxicity Risk Assessment. 1996. https://www.epa.gov/sites/default/files/2014-11/documents/guidelines_repro_toxicity.pdf (accessed 2022-08-10).

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67. 67

    U.S. Environmental Protection Agency. Guidelines for Carcinogen Risk Assessment. 2005. https://www3.epa.gov/airtoxics/cancer_guidelines_final_3-25-05.pdf (accessed 2021-08-04).

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68. 68

    Choi, Y. J.; Park, J. W.; Lim, Y.; Seo, S.; Hwang, D. Y. In vivo impact assessment of orally administered polystyrene nanoplastics: biodistribution, toxicity, and inflammatory response in mice. Nanotoxicology 2021, 15 (9), 1180,  DOI: 10.1080/17435390.2021.1996650

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69. 69

    Choi, Y. J.; Park, J. W.; Kim, J. E.; Lee, S. J.; Gong, J. E.; Jung, Y. S.; Seo, S.; Hwang, D. Y. Novel characterization of constipation phenotypes in icr mice orally administrated with polystyrene microplastics. Int. J. Mol. Sci. 2021, 22 (11), 5845,  DOI: 10.3390/ijms22115845

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70. 70

    Jin, Y.; Lu, L.; Tu, W.; Luo, T.; Fu, Z. Impacts of polystyrene microplastic on the gut barrier, microbiota and metabolism of mice. Sci. Total Environ. 2019, 649, 308– 317,  DOI: 10.1016/j.scitotenv.2018.08.353

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    70

    Impacts of polystyrene microplastic on the gut barrier, microbiota and metabolism of mice

    Jin, Yuanxiang; Lu, Liang; Tu, Wenqing; Luo, Ting; Fu, Zhengwei

    Science of the Total Environment (2019), 649 (), 308-317CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)

    Microplastics (MPs), which are new environmental pollutants with a diam. of <5 mm, have received wide attention in recent years. However, there are still very limited data regarding the risks of MPs to animals, esp. higher mammals. In this study, we exposed male mice to 5 μm pristine and fluorescent polystyrene MP for six weeks. The results showed that the polystyrene MP was obsd. in the guts of mice and could reduce the intestinal mucus secretion and cause damage the intestinal barrier function. In addn., high-throughput sequencing of the V3-V4 region of the 16S rRNA gene was used to explore the change of the gut microbiota compn. in the cecal content. At the phylum level, the content of Actinobacteria decreased significantly in the polystyrene MP-treated group. The PD whole-tree indexes of the alpha diversity and principal component anal. (PCA) of the beta diversity indicated that the diversity of gut microbiota was altered after polystyrene MP exposure. At the genus level, a total of 15 types of bacteria changed significantly after exposure to polystyrene MP. Furthermore, the predicted KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic pathway differences indicated that the main metabolic pathways of the functional genes in the microbial community were significantly influenced by the polystyrene MP. In addn., indexes of amino acid metab. and bile acid metab. in the serum were analyzed after polystyrene MP exposure. These results indicated that polystyrene MP caused metabolic disorders. In conclusion, the polystyrene MP induced gut microbiota dysbiosis, intestinal barrier dysfunction and metabolic disorders in mice. This study provided more data on the toxicity of MPs in a terrestrial organism to aid in the assessment of the health risks of polystyrene MP to animals.

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71. 71

    Lu, L.; Wan, Z.; Luo, T.; Fu, Z.; Jin, Y. Polystyrene microplastics induce gut microbiota dysbiosis and hepatic lipid metabolism disorder in mice. Sci. Total Environ. 2018, 631–632, 449– 458,  DOI: 10.1016/j.scitotenv.2018.03.051

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    71

    Polystyrene microplastics induce gut microbiota dysbiosis and hepatic lipid metabolism disorder in mice

    Lu, Liang; Wan, Zhiqin; Luo, Ting; Fu, Zhengwei; Jin, Yuanxiang

    Science of the Total Environment (2018), 631-632 (), 449-458CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)

    Microplastic (MP) has become a concerning global environmental problem. It is toxic to aquatic organisms and can spread through the food chain to ultimately pose a threat to humans. In the environment, MP can interact with microbes and act as a microbial habitat. However, effects of polystyrene MP on the gut microbiota in mammals remain unclear. Here, male mice were exposed to two different sizes of polystyrene MP for 5 wk to explore its effect. The authors obsd. that oral exposure to 1000 μg/L of 0.5 and 50 μm polystyrene MP decreased the body, liver and lipid wts. in mice. Mucus secretion in the gut decreased in both sizes of polystyrene MP-treated groups. Regarding the gut microbiota, at the phylum level, polystyrene MP exposure decreased the relative abundances of Firmicutes and α-Proteobacteria in the feces. Furthermore, high throughput sequencing of the V3-V4 region of the 16S rRNA gene revealed significant changes in the richness and diversity of the gut microbiota in the cecums of polystyrene MP-treated mice. At the genus level, a total of 6 and 8 types of bacteria changed in the 0.5 and 50 μm polystyrene MP-treated groups, resp. Furthermore, an operational taxonomic unit (OTU) anal. identified that 310 and 160 gut microbes were changed in the 0.5 and 50 μm polystyrene MP-treated groups, resp. In addn., the hepatic triglyceride (TG) and total cholesterol (TCH) levels decreased in both 1000 μg/L 0.5 and 50 μm polystyrene MP-treated groups. Correspondingly, the relative mRNA levels of some key genes related to lipogenesis and TG synthesis decreased in the liver and epididymal fat. These results indicated that polystyrene MP could modify the gut microbiota compn. and induce hepatic lipid disorder in mice; while the mouse is a common mammal model, consequently, the health risks of MP to animals should not be ignored.

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72. 72

    An, R.; Wang, X.; Yang, L.; Zhang, J.; Wang, N.; Xu, F.; Hou, Y.; Zhang, H.; Zhang, L. Polystyrene microplastics cause granulosa cells apoptosis and fibrosis in ovary through oxidative stress in rats. Toxicology 2021, 449, 152665,  DOI: 10.1016/j.tox.2020.152665

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    72

    Polystyrene microplastics cause granulosa cells apoptosis and fibrosis in ovary through oxidative stress in rats

    An, Ru; Wang, Xifeng; Yang, Long; Zhang, Jinjin; Wang, Nana; Xu, Feibo; Hou, Yun; Zhang, Hongqin; Zhang, Lianshuang

    Toxicology (2021), 449 (), 152665CODEN: TXCYAC; ISSN:0300-483X. (Elsevier Ltd.)

    Microplastics (MPs) are receiving increased attention as a harmful environmental pollutant. Studies have investigated that MPs have reproductive toxicity, but the mechanism is little known. Here, we aimed to investigate the effects of polystyrene microplastics (PS-MPs) on ovary in rats and the underlying mol. mechanisms. in vivo, thirty-two female Wistar rats were exposed to 0.5μm PS-MPs at different concns. (0, 0.015, 0.15 and 1.5 mg/d) for 90 days. And then, all animals were sacrificed, ovaries and blood were collected for testing. in vitro, granulosa cells (GCs) were sepd. from rat ovary and treated with 0,1,5,25μg/mL PS-MPs and reactive oxygen species (ROS) inhibitor N-Acetyl-L-cysteine (NAC) resp. Our results showed that PS-MPs could enter into GCs and result in the reducing of growing follicles no. And the ELISA (ELISA) manifested that PS-MPs could obviously decrease the level of anti-Mullerian hormone (AMH). In addn., PS-MPs induced oxidative stress, apoptosis of GCs and ovary fibrosis evidenced by assay kits, flow cytometry, immunohistochem., Masson's trichrome and Sirius red staining. Moreover, the western blot assay manifested that PS-MPs exposure significantly increased the expression levels of Wnt/β-Catenin signaling pathways-related proteins (Wnt, β-catenin, p-β-catenin) and the main fibrosis markers transforming growth factor-β (TGF-β), fibronectin, α-smooth muscle actin (α-SMA). Addnl., the expression levels of Wnt and p-β-catenin, apoptosis of GCs decreased after NAC treatment. In summary, polystyrene microplastics cause fibrosis via Wnt/β-Catenin signaling pathway activation and granulosa cells apoptosis of ovary through oxidative stress in rats, both of which ultimately resulted in decrease of ovarian reserve capacity.

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73. 73

    Hou, J.; Lei, Z.; Cui, L.; Hou, Y.; Yang, L.; An, R.; Wang, Q.; Li, S.; Zhang, H.; Zhang, L. Polystyrene microplastics lead to pyroptosis and apoptosis of ovarian granulosa cells via NLRP3/Caspase-1 signaling pathway in rats. Ecotoxicology and Environmental Safety 2021, 212, 112012  DOI: 10.1016/j.ecoenv.2021.112012

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74. 74

    Li, S.; Wang, Q.; Yu, H.; Yang, L.; Sun, Y.; Xu, N.; Wang, N.; Lei, Z.; Hou, J.; Jin, Y.; Zhang, H.; Li, L.; Xu, F.; Zhang, L. Polystyrene microplastics induce blood-testis barrier disruption regulated by the MAPK-Nrf2 signaling pathway in rats. Environ. Sci. Pollut. Res. 2021, 28 (35), 47921,  DOI: 10.1007/s11356-021-13911-9

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75. 75

    Djouina, M.; Vignal, C.; Dehaut, A.; Caboche, S.; Hirt, N.; Waxin, C.; Himber, C.; Beury, D.; Hot, D.; Dubuquoy, L.; Launay, D.; Duflos, G.; Body-Malapel, M. Oral exposure to polyethylene microplastics alters gut morphology, immune response, and microbiota composition in mice. Environmental Research 2022, 212, 113230,  DOI: 10.1016/j.envres.2022.113230

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76. 76

    Wen, S.; Zhao, Y.; Liu, S.; Chen, Y.; Yuan, H.; Xu, H. Polystyrene microplastics exacerbated liver injury from cyclophosphamide in mice: Insight into gut microbiota. Sci. Total Environ. 2022, 840, 156668,  DOI: 10.1016/j.scitotenv.2022.156668

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    76

    Polystyrene microplastics exacerbated liver injury from cyclophosphamide in mice: Insight into gut microbiota

    Wen, Siyue; Zhao, Yu; Liu, Shanji; Chen, Yanbiao; Yuan, Hongbin; Xu, Hengyi

    Science of the Total Environment (2022), 840 (), 156668CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)

    Microplastics (MPs) have infiltrated human food system globally, and the latent health risks have been well-described. However, the impact of pre-consumed MPs on liver resistance to foreign robust stimuli remains unclear. In this study, we developed a mouse model drinking roughly 18 and 180μg/kg/day polystyrene MPs for 90 days, then i.p. injected mice with 80 mg/kg cyclophosphamide (CTX) to investigate whether chronic pre-exposure to MPs aggravates hepatoxicity induced by CTX. Slight liver injury was found in single CTX-treated mice, while more significant liver histopathol. damage, inflammation and oxidative stress elicited by CTX were obsd. in pre-drinking MPs mice. Moreover, chronic exposure of MPs induced remarkable colonic impairments (e.g., leaky gut, mild inflammation and repressed antioxidant activity) as well as gut microbiota perturbation, which manifested pos. assocn. with aggravated hepatotoxicity via spearman correlation anal. Fecal microbiota transplantation (FMT) trail was conducted to ulteriorly demonstrate the crit. role of MPs-altered gut bacteria in exaggerated liver susceptibility to CTX stimulation. In conclusion, our study provided an insight that the adverse impact of MPs could be best revealed when animals suffering attack from hazardous substance. It also contributes to comprehensive assessment of health risk from environmentally pervasive MPs.

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77. 77

    Deng, Y.; Chen, H.; Huang, Y.; Zhang, Y.; Ren, H.; Fang, M.; Wang, Q.; Chen, W.; Hale, R. C.; Galloway, T. S.; Chen, D. Long-Term Exposure to Environmentally Relevant Doses of Large Polystyrene Microplastics Disturbs Lipid Homeostasis via Bowel Function Interference. Environ. Sci. Technol. 2022, 56 (22), 15805– 15817,  DOI: 10.1021/acs.est.1c07933

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    77

    Long-Term Exposure to Environmentally Relevant Doses of Large Polystyrene Microplastics Disturbs Lipid Homeostasis via Bowel Function Interference

    Deng, Yongfeng; Chen, Hexia; Huang, Yichao; Zhang, Yan; Ren, Hongqiang; Fang, Mingliang; Wang, Qing; Chen, Wen; Hale, Robert C.; Galloway, Tamara S.; Chen, Da

    Environmental Science & Technology (2022), 56 (22), 15805-15817CODEN: ESTHAG; ISSN:1520-5851. (American Chemical Society)

    The question of whether long-term chronic exposure to microplastics (MPs) could induce dose- and size-dependent adverse effects in mammals remains controversial and poorly understood. Our study explored potential health risks from dietary exposure to environmentally relevant doses of polystyrene (PS) MPs, through a mouse model and integrated analyses of the interruptions of fecal microbial metagenomes and plasma lipidomes. After 21 wk of exposure to the MPs (40-100μm), mice mainly exhibited gut microbiota dysbiosis, tissue inflammation, and plasma lipid metab. disorder, although no notable accumulation of MPs was obsd. in the gut or liver. The change of the relative abundance of microbiota was strongly assocd. with the exposure dose and size of MPs while less significant effects were obsd. in gut damage and abnormal lipid metab. Moreover, multiomics data suggested that the host abnormal lipid metab. was closely related to bowel function disruptions, including gut microbiota dysbiosis, increased gut permeability, and inflammation induced by MPs. We revealed for the first time that even without notable accumulation in mouse tissues, long-term exposure to MPs at environmentally relevant doses could still induce widespread health risks. This raises concern on the health risks from the exposure of humans and other mammals to environmentally relevant dose MPs.

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78. 78

    Li, B.; Ding, Y.; Cheng, X.; Sheng, D.; Xu, Z.; Rong, Q.; Wu, Y.; Zhao, H.; Ji, X.; Zhang, Y. Polyethylene microplastics affect the distribution of gut microbiota and inflammation development in mice. Chemosphere 2020, 244, 125492  DOI: 10.1016/j.chemosphere.2019.125492

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    Polyethylene microplastics affect the distribution of gut microbiota and inflammation development in mice

    Li, Boqing; Ding, Yunfei; Cheng, Xue; Sheng, Dandan; Xu, Zheng; Rong, Qianyu; Wu, Yulong; Zhao, Huilin; Ji, Xiaofei; Zhang, Ying

    Chemosphere (2020), 244 (), 125492CODEN: CMSHAF; ISSN:0045-6535. (Elsevier Ltd.)

    Environmental pollution caused by plastics has become a public health problem. However, the effect of microplastics on gut microbiota, inflammation development and their underlying mechanisms are not well characterized. In the present study, we assessed the effect of exposure to different amts. of polyethylene microplastics (6, 60, and 600μg/day for 5 consecutive weeks) in a C57BL/6 mice model. Treatment with a high concn. of microplastics increased the nos. of gut microbial species, bacterial abundance, and flora diversity. Feeding groups showed a significant increase in Staphylococcus abundance alongside a significant decrease in Parabacteroides abundance, as compared to the blank (untreated) group. In addn., serum levels of interleukin-1α in all feeding groups were significantly greater than that in the blank group. Of note, treatment with microplastics decreased the percentage of Th17 and Treg cells among CD4+ cells, while no significant difference was obsd. between the blank and treatment groups with respect to the Th17/Treg cell ratio. The intestine (colon and duodenum) of mice fed high-concn. microplastics showed obvious inflammation and higher TLR4, AP-1, and IRF5 expression. Thus, polyethylene microplastics can induce intestinal dysbacteriosis and inflammation, which provides a theor. basis for the prevention and treatment of microplastics-related diseases.

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79. 79

    Li, L.; Lv, X.; He, J.; Zhang, L.; Li, B.; Zhang, X.; Liu, S.; Zhang, Y. Chronic exposure to polystyrene nanoplastics induces intestinal mechanical and immune barrier dysfunction in mice. Ecotoxicology and Environmental Safety 2024, 269, 115749  DOI: 10.1016/j.ecoenv.2023.115749

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80. 80

    Chen, S.; Li, S. W.; Gu, X. Y.; Ma, L. Q.; Zhou, D. M.; Li, H. B. Reduced dietary Ca, Cu, Zn, Mn, and Mg bioavailability but increased Fe bioavailability with polyethylene microplastic ingestion in a mouse model: Changes in intestinal permeability and gut metabolites. Sci. Total Environ. 2023, 885, 163853  DOI: 10.1016/j.scitotenv.2023.163853

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81. 81

    Smith, M. T.; Guyton, K. Z.; Gibbons, C. F.; Fritz, J. M.; Portier, C. J.; Rusyn, I.; DeMarini, D. M.; Caldwell, J. C.; Kavlock, R. J.; Lambert, P. F.; Hecht, S. S.; Bucher, J. R.; Stewart, B. W.; Baan, R. A.; Cogliano, V. J.; Straif, K. Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis. Environ. Health Perspect. 2016, 124 (6), 713– 721,  DOI: 10.1289/ehp.1509912

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    Key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis

    Smith, Martyn T.; Guyton, Kathryn Z.; Gibbons, Catherine F.; Fritz, Jason M.; Portier, Christopher J.; Rusyn, Ivan; De Marini, David M.; Caldwell, Jane C.; Kavlock, Robert J.; Lambert, Paul F.; Hecht, Stephen S.; Bucher, John R.; Stewart, Bernard W.; Baan, Robert A.; Cogliano, Vincent J.; Straif, Kurt

    Environmental Health Perspectives (2016), 124 (6), 713-721CODEN: EVHPAZ; ISSN:1552-9924. (U. S. Department of Health and Human Services, National Institutes of Health)

    BACKGROUND: A recent review by the International Agency for Research on Cancer (IARC) updated the assessments of the > 100 agents classified as Group 1, carcinogenic to humans (IARC Monographs Vol. 100, parts A-F). This exercise was complicated by the absence of a broadly accepted, systematic method for evaluating mechanistic data to support conclusions regarding human hazard from exposure to carcinogens. OBJECTIVES AND METHODS: IARC therefore convened two workshops in which an international Working Group of experts identified 10 key characteristics, one or more of which are commonly exhibited by established human carcinogens. DISCUSSION: These characteristics provide the basis for an objective approach to identifying and organizing results from pertinent mechanistic studies. The 10 characteristics are the abilities of an agent to 1) act as an electrophile either directly or after metabolic activation; 2) be genotoxic; 3) alter DNA repair or cause genomic instability; 4) induce epigenetic alterations; 5) induce oxidative stress; 6) induce chronic inflammation; 7) be immunosuppressive; 8) modulate receptor mediated effects; 9) cause immortalization; and 10) alter cell proliferation, cell death, or nutrient supply. CONCLUSION: We describe the use of the 10 key characteristics to conduct a systematic literature search focused on relevant end points and construct a graphical representation of the identified mechanistic information. Next, we use benzene and polychlorinated biphenyls as examples to illustrate how this approach may work in practice. The approach described is similar in many respects to those currently being implemented by the U.S. EPA's Integrated Risk Information System Program and the U.S. National Toxicol. Program.

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82. 82

    Zhang, Y.; Wang, X.; Zhao, Y.; Zhao, J.; Yu, T.; Yao, Y.; Zhao, R.; Yu, R.; Liu, J.; Su, J. Reproductive toxicity of microplastics in female mice and their offspring from induction of oxidative stress. Environmental Pollution (Barking, Essex: 1987) 2023, 327, 121482  DOI: 10.1016/j.envpol.2023.121482

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83. 83

    Saeed, A.; Akhtar, M. F.; Saleem, A.; Akhtar, B.; Sharif, A. Reproductive and metabolic toxic effects of polystyrene microplastics in adult female Wistar rats: a mechanistic study. Environ. Sci. Pollut Res. Int. 2023, 30 (22), 63185– 63199,  DOI: 10.1007/s11356-023-26565-6

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84. 84

    Jin, H.; Yan, M.; Pan, C.; Liu, Z.; Sha, X.; Jiang, C.; Li, L.; Pan, M.; Li, D.; Han, X.; Ding, J. Chronic exposure to polystyrene microplastics induced male reproductive toxicity and decreased testosterone levels via the LH-mediated LHR/cAMP/PKA/StAR pathway. Particle and Fibre Toxicology 2022, 19 (1), 13,  DOI: 10.1186/s12989-022-00453-2

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85. 85

    Hou, B.; Wang, F.; Liu, T.; Wang, Z. Reproductive toxicity of polystyrene microplastics: In vivo experimental study on testicular toxicity in mice. J. Hazard. Mater. 2021, 405, 124028,  DOI: 10.1016/j.jhazmat.2020.124028

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    85

    Reproductive toxicity of polystyrene microplastics: In vivo experimental study on testicular toxicity in mice

    Hou, Baolian; Wang, Fangyi; Liu, Tao; Wang, Zhiping

    Journal of Hazardous Materials (2021), 405 (), 124028CODEN: JHMAD9; ISSN:0304-3894. (Elsevier B.V.)

    Microplastics (MPS) are widespread in our environment and have a potential impact on the reproductive development of humans and mammals. In this study, we evaluated the effect of 5μm polystyrene microplastics(PS-MPS) on spermatogenesis in mice. The damage by PS-MPS to epididymal sperm was studied using blood cell counts. The results showed that the no. of viable epididymis sperm after PS-MPS exposure was significantly reduced. Using Duff-Quik staining, we found that the PS-MPS exposure increased the rate of sperm deformity. The testis is an important organ responsible for normal spermatogenesis. HE and TUNEL staining showed atrophy, shedding, and apoptosis of sperm cells at all levels of the testis after exposure to PS-MPS. Western blot and qPCR anal. were used to detect Nrf2/HO-1 and NF-κB. The results showed that after PS-MPS exposure, the expression of the pro-inflammatory mol. NF-κB and that of the inflammatory factors interleukin (IL)-1β and IL-6 increased significantly, whereas that of the anti-inflammatory mol. Nrf2/HO-1 decreased. These results indicate that the abnormal sperm quality in ICR mice caused by PS-MPS exposure is closely related to the Nrf2/HO-1/NF-κB pathway.

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86. 86

    Huang, T.; Zhang, W.; Lin, T.; Liu, S.; Sun, Z.; Liu, F.; Yuan, Y.; Xiang, X.; Kuang, H.; Yang, B.; Zhang, D. Maternal exposure to polystyrene nanoplastics during gestation and lactation induces hepatic and testicular toxicity in male mouse offspring. Food Chem. Toxicol. 2022, 160, 112803  DOI: 10.1016/j.fct.2021.112803

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    86

    Maternal exposure to polystyrene nanoplastics during gestation and lactation induces hepatic and testicular toxicity in male mouse offspring

    Huang, Tao; Zhang, Wenjuan; Lin, Tingting; Liu, Shujuan; Sun, Zhangbei; Liu, Fangming; Yuan, Yangyang; Xiang, Xiting; Kuang, Haibin; Yang, Bei; Zhang, Dalei

    Food and Chemical Toxicology (2022), 160 (), 112803CODEN: FCTOD7; ISSN:0278-6915. (Elsevier Ltd.)

    Nanoplastics have raised considerable concerns since their ubiquity in the environment and potential hazard to health. It has been proven that polystyrene nanoparticles (PS-NPs) can be maternally transferred to the offspring. In this study, mice were exposed gestationally and lactationally to PS-NPs (size 100 nm) at different doses (0.1, 1 and 10 mg/L) to investigate the trans-generational poisonousness. Our data illustrated that maternal PS-NPs exposure in pregnancy and lactation resulted in a decline in birth and postnatal body wt. in offspring mice. Furthermore, high-dose PS-NPs reduced liver wt., triggered oxidative stress, caused inflammatory cell infiltration, up-regulated proinflammatory cytokine expression, and disturbed glycometabolism in the liver of male offspring mice. In addn., pre- and postnatal PS-NPs exposure diminished testis wt., disrupted seminiferous epithelium and decreased sperm count in mouse offspring. Moreover, PS-NPs induced testicular oxidative injury, as presented by increased malondialdehyde generation and altered superoxide dismutase and catalase activities in the testis of offspring mice. These findings declared that maternal exposure to PS-NPs in pregnancy and lactation can cause hepatic and testicular toxicity in male mouse pups, which put forward new understanding into the detrimental effects of nanoplastics on mammalian offspring.

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87. 87

    Zhao, T.; Shen, L.; Ye, X.; Bai, G.; Liao, C.; Chen, Z.; Peng, T.; Li, X.; Kang, X.; An, G. Prenatal and postnatal exposure to polystyrene microplastics induces testis developmental disorder and affects male fertility in mice. Journal of Hazardous Materials 2023, 445, 130544  DOI: 10.1016/j.jhazmat.2022.130544

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    There is no corresponding record for this reference.
88. 88

    Aghaei, Z.; Mercer, G. V.; Schneider, C. M.; Sled, J. G.; Macgowan, C. K.; Baschat, A. A.; Kingdom, J. C.; Helm, P. A.; Simpson, A. J.; Simpson, M. J.; Jobst, K. J.; Cahill, L. S. Maternal exposure to polystyrene microplastics alters placental metabolism in mice. Metabolomics: Official Journal of the Metabolomic Society 2023, 19 (1), 1,  DOI: 10.1007/s11306-022-01967-8

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    There is no corresponding record for this reference.
89. 89

    Wu, D.; Zhang, M.; Bao, T. T.; Lan, H. Long-term exposure to polystyrene microplastics triggers premature testicular aging. Part Fibre Toxicol. 2023, 20 (1), 35,  DOI: 10.1186/s12989-023-00546-6

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    There is no corresponding record for this reference.
90. 90

    Taş, B. M.; Tuna, A.; Başaran Kankılıç, G.; Koçak, F. M.; Şencan, Z.; Cömert, E.; Bayar Muluk, N. Role of Microplastics in Chronic Rhinosinusitis Without Nasal Polyps. Laryngoscope 2023, 134 (3), 1077– 1080,  DOI: 10.1002/lary.30926

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    There is no corresponding record for this reference.
91. 91

    Lim, D.; Jeong, J.; Song, K. S.; Sung, J. H.; Oh, S. M.; Choi, J. Inhalation toxicity of polystyrene micro(nano)plastics using modified OECD TG 412. Chemosphere 2021, 262, 128330  DOI: 10.1016/j.chemosphere.2020.128330

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    92

    Inhalation toxicity of polystyrene micro(nano)plastics using modified OECD TG 412

    Lim, Dongyoung; Jeong, Jaeseong; Song, Kyung Seuk; Sung, Jae Hyuck; Oh, Seung Min; Choi, Jinhee

    Chemosphere (2021), 262 (), 128330CODEN: CMSHAF; ISSN:0045-6535. (Elsevier Ltd.)

    Recently, there have been reports that many microplastics are found in the air, which has raised concerns about their toxicity. To date, however, only limited research has investigated the effects of micro(nano)plastics on human health, and even less the potential for inhalation toxicity. To fill this research gap, we investigated the potential inhalation toxicity of micro(nano)plastics using a modified OECD Guideline for Testing of Chems. No. 412 '28-Day (subacute) inhalation toxicity study' using a whole-body inhalation system. Sprague-Dawley rats were exposed to three different exposure concns. of polystyrene micro(nano)plastics (PSMPs), as well as control, for 14 days of inhalation exposure. After 14 days, alterations were obsd. on sevral endpoints in physiol., serum biochem., hematol., and respiratory function markers measured on the samples exposed to PSMPs. On the other hand, the expression of inflammatory proteins (TGF-β and TNF-α) increased in the lung tissue in an exposure concn.-dependent manner. The overall results indicate that 14-day inhalation exposure of PSMPs to rats has a more pronounced effect at the mol. level than at the organismal one. These results suggest that if the exposure sustained, alterations at the mol. level may lead to subsequent alterations at the higher levels, and consequently, the health risks of inhalation exposed micro(nano)plastics should not be neglected.

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92. 92

    Li, Y.; Shi, T.; Li, X.; Sun, H.; Xia, X.; Ji, X.; Zhang, J.; Liu, M.; Lin, Y.; Zhang, R.; Zheng, Y.; Tang, J. Inhaled tire-wear microplastic particles induced pulmonary fibrotic injury via epithelial cytoskeleton rearrangement. Environ. Int. 2022, 164, 107257,  DOI: 10.1016/j.envint.2022.107257

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    93

    Inhaled tire-wear microplastic particles induced pulmonary fibrotic injury via epithelial cytoskeleton rearrangement

    Li, Yanting; Shi, Teng; Li, Xin; Sun, Huimin; Xia, Xiaowen; Ji, Xiaoya; Zhang, Jianzhong; Liu, Meike; Lin, Yongfeng; Zhang, Rong; Zheng, Yuxin; Tang, Jinglong

    Environment International (2022), 164 (), 107257CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)

    Tire wear microplastic particles (TWMPs) are emerging microplastic pollutants that have gained increasing attention lately. However, the health effect of inhaled airborne TWMPs has never been explored before and may already be included in particulate matter morbidity and mortality. Here, we endeavored to address the preliminary study of TWMP inhalation-induced pulmonary toxic effects and its epigenetic mechanisms in C57BL/6 mice. As a result, restricted ventilatory dysfunction and fibrotic pathol. changes were obsd. in TWMP-treaded mice. Further research found that attenuation of miR-1a-3p plays an important role in TWMP-induced lung injury. Results from in vitro study confirmed that cytoskeleton regulatory gene twinfilin-1 was one of the target genes of miR-1a-3p, and involved in cytoskeleton rearrangement caused by TWMP exposure. Mechanistically, miR-1a-3p inhibited the F-actin formation by targeting cytoskeletal regulatory proteins twinfilin-1, leading to TWMP-induced pulmonary fibrotic injury. While we are in the very early stages of explaining the role of epigenetics in TWMP-induced lung injury, the potential for the use of epigenetic marks as biomarkers is high and discoveries made in this field will likely bring us closer to better understanding this crucial mechanism.

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93. 93

    Woo, J.-H.; Seo, H. J.; Lee, J.-Y.; Lee, I.; Jeon, K.; Kim, B.; Lee, K. Polypropylene nanoplastic exposure leads to lung inflammation through p38-mediated NF-κB pathway due to mitochondrial damage. Particle and Fibre Toxicology 2023, 20 (1), 2,  DOI: 10.1186/s12989-022-00512-8

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94. 94

    Yang, S.; Zhang, T.; Ge, Y.; Yin, L.; Pu, Y.; Liang, G. Inhalation exposure to polystyrene nanoplastics induces chronic obstructive pulmonary disease-like lung injury in mice through multi-dimensional assessment. Environ. Pollut. 2024, 347, 123633  DOI: 10.1016/j.envpol.2024.123633

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95. 95

    Wu, Q.; Liu, C.; Liu, D.; Wang, Y.; Qi, H.; Liu, X.; Zhang, Y.; Chen, H.; Zeng, Y.; Li, J. Polystyrene nanoplastics-induced lung apoptosis and ferroptosis via ROS-dependent endoplasmic reticulum stress. Science of the Total Environment 2024, 912, 169260  DOI: 10.1016/j.scitotenv.2023.169260

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96. 96

    Li, X.; Zhang, T.; Lv, W.; Wang, H.; Chen, H.; Xu, Q.; Cai, H.; Dai, J. Intratracheal administration of polystyrene microplastics induces pulmonary fibrosis by activating oxidative stress and Wnt/β-catenin signaling pathway in mice. Ecotoxicol. Environ. Saf. 2022, 232, 113238,  DOI: 10.1016/j.ecoenv.2022.113238

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    97

    Intratracheal administration of polystyrene microplastics induces pulmonary fibrosis by activating oxidative stress and Wnt/β-catenin signaling pathway in mice

    Li, Xuran; Zhang, Tongtong; Lv, Wenting; Wang, Hui; Chen, Haoran; Xu, Qinghua; Cai, Hourong; Dai, Jinghong

    Ecotoxicology and Environmental Safety (2022), 232 (), 113238CODEN: EESADV; ISSN:0147-6513. (Elsevier B.V.)

    Polystyrene microplastics (PS-MPs) are emerging pollutants that are absorbed by organisms. Due to their small vol. and strong biol. permeability, they affect the biol. functions of cells. In recent years, several studies have detected PS-MPs in air samples, which may damage the human respiratory system following inhalation. The Masson trichrome staining, immunofluorescence, and western blotting assays were conducted to analyze the effects of PS-MPs on pulmonary fibrosis. Alveolar epithelial injuries were assessed through confocal microscopy, and the levels of SOD and GSH were used to evaluate oxidative stress. Our analyzes demonstrated that inhalation of the PS-MPs induces pulmonary fibrosis in a dose-dependent manner in mice. In high dose group (6.25 mg/kg), the PS-MPs significantly increased the expression of α-SMA, Vimentin and Col1a (p < 0.05). Immunofluorescence assays showed decreased levels of SP-C and increased levels of KL-6 in the PS-MPs group. The suppression of SOD (1.46 times) and GSH-Px (2.27 times) indicated that inhalation of microplastics triggered intensive oxidative stress in lungs. Moreover, there was activation of the Wnt/β-catenin signaling pathway in the PS-MPs group. In addn., the data showed that antioxidant melatonin (50 mg/kg) alleviated the PS-MPs-induced pulmonary fibrosis. Taken together, our anal. demonstrated that inhalation of polystyrene microplastics induces pulmonary fibrosis via activation of oxidative stress and Wnt/β-catenin signaling pathway in mice.

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97. 97

    Fan, Z.; Xiao, T.; Luo, H.; Chen, D.; Lu, K.; Shi, W.; Sun, C.; Bian, Q. A study on the roles of long non-coding RNA and circular RNA in the pulmonary injuries induced by polystyrene microplastics. Environ. Int. 2022, 163, 107223,  DOI: 10.1016/j.envint.2022.107223

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    98

    A study on the roles of long non-coding RNA and circular RNA in the pulmonary injuries induced by polystyrene microplastics

    Fan Zi; Luo Hangjun; Xiao Tian; Chen Dongya; Lu Kuikui; Shi Weiqing; Sun Cheng; Bian Qian

    Environment international (2022), 163 (), 107223 ISSN:.

    Microplastics (MPs) pollution has become a global concern due to its close relation to the environment and human health. Recently, more and more studies have pointed out the existence of MPs in the air, but its potential inhalation toxicity is unclear. Polystyrene Microplastics (PS-MPs) is one of the representative MPs. Besides, non-coding RNA plays crucial roles in regulating gene expression. Therefore, this study aims to provide new insights into the molecular exploration of PS-MPs inhalation. In this study, Sprague Dawley SD rats were treated with 100 nm, 500 nm, 1 μm and 2.5 μm PS-MPs for three days. And then intra-tracheal instillation of saline or 100 nm PS-MPs with 0, 0.5, 1 and 2 mg/200 μL were performed in SD rats every two days for two consecutive weeks. The deposition of PS-MPs was observed through immunofluorescence. Lung histological alternations were observed in haematoxylin and eosin (H&E) staining sections. The expressions of pro-inflammatory cytokines were quantified by ELISA and qPCR. Genome-wide transcriptomic profiling of long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) in rats lung were done by ribosomal RNA depleted RNA sequencing and verified by qRT-PCR. We observed that 100 nm and 1 μm PS-MPs could deposite in the lungs. In addition, pathological examination shows alveolar destruction and bronchial epithelium arranged in a mess in PS-MPs groups. Furthermore, the expressions of pro-inflammatory cytokines IL-6, TNF-α and IL-1β were upregulated in PS-MPs exposed rats. Sequencing results showed that 269 circRNAs and 109 lncRNAs were differentially expressed in lung tissue of the saline and PS-MPs exposed rats. The upregulated expressions of lncRNA XLOC_031479, circRNA 014924 and circRNA 006603 and the downregulated expressions of lncRNA XLOC_014188 and circ003982 were identified by qRT-PCR in MPs group. The identified novel circRNAs and lncRNAs may paly important role in the development of lung inflammation caused by PS-MPs.

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98. 98

    Li, X.; Zhang, T.; Lv, W.; Wang, H.; Chen, H.; Xu, Q.; Cai, H.; Dai, J. Intratracheal administration of polystyrene microplastics induces pulmonary fibrosis by activating oxidative stress and Wnt/β-catenin signaling pathway in mice. Ecotoxicol. Environ. Saf. 2022, 232, 113238,  DOI: 10.1016/j.ecoenv.2022.113238

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    99

    Intratracheal administration of polystyrene microplastics induces pulmonary fibrosis by activating oxidative stress and Wnt/β-catenin signaling pathway in mice

    Li, Xuran; Zhang, Tongtong; Lv, Wenting; Wang, Hui; Chen, Haoran; Xu, Qinghua; Cai, Hourong; Dai, Jinghong

    Ecotoxicology and Environmental Safety (2022), 232 (), 113238CODEN: EESADV; ISSN:0147-6513. (Elsevier B.V.)

    Polystyrene microplastics (PS-MPs) are emerging pollutants that are absorbed by organisms. Due to their small vol. and strong biol. permeability, they affect the biol. functions of cells. In recent years, several studies have detected PS-MPs in air samples, which may damage the human respiratory system following inhalation. The Masson trichrome staining, immunofluorescence, and western blotting assays were conducted to analyze the effects of PS-MPs on pulmonary fibrosis. Alveolar epithelial injuries were assessed through confocal microscopy, and the levels of SOD and GSH were used to evaluate oxidative stress. Our analyzes demonstrated that inhalation of the PS-MPs induces pulmonary fibrosis in a dose-dependent manner in mice. In high dose group (6.25 mg/kg), the PS-MPs significantly increased the expression of α-SMA, Vimentin and Col1a (p < 0.05). Immunofluorescence assays showed decreased levels of SP-C and increased levels of KL-6 in the PS-MPs group. The suppression of SOD (1.46 times) and GSH-Px (2.27 times) indicated that inhalation of microplastics triggered intensive oxidative stress in lungs. Moreover, there was activation of the Wnt/β-catenin signaling pathway in the PS-MPs group. In addn., the data showed that antioxidant melatonin (50 mg/kg) alleviated the PS-MPs-induced pulmonary fibrosis. Taken together, our anal. demonstrated that inhalation of polystyrene microplastics induces pulmonary fibrosis via activation of oxidative stress and Wnt/β-catenin signaling pathway in mice.

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99. 99

    He, Y.; Yin, R. The reproductive and transgenerational toxicity of microplastics and nanoplastics: A threat to mammalian fertility in both sexes. J. of Applied Toxicology 2024, 44 (1), 66– 85,  DOI: 10.1002/jat.4510

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100. 100

     MacGarvin, M.; Lambert, B.; Infante, P.; Greenberg, M.; Gee, D.; Koppe, J. G.; Keys, J.; Farman, J.; Ibarreta, D.; Swan, S. H.; Edqvist, L. E.; Pedersen, K. B.; Semb, A.; von Krauss, M. K.; Harremoëss, P. J.; Langston, W. J.; Bridges, J. W.; Bridges, O.; van Zwanenberg, P.; Millstone, E. Late lessons from early warnings: The precautionary principle 1896–2000. European Environment Agency, 2001. https://www.eea.europa.eu/publications/environmental_issue_report_2001_22.

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101. 101

     Maffini, M. V.; Rayasam, S. D. G.; Axelrad, D. A.; Birnbaum, L. S.; Cooper, C.; Franjevic, S.; MacRoy, P. M.; Nachman, K. E.; Patisaul, H. B.; Rodgers, K. M.; Rossi, M. S.; Schettler, T.; Solomon, G. M.; Woodruff, T. J. Advancing the science on chemical classes. Environ. Health 2023, 21 (Suppl. 1), 120,  DOI: 10.1186/s12940-022-00919-y

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102. 102

     United States Code, 2006 Edition, Supplement 5, Title 15 - COMMERCE AND TRADE. CHAPTER 53 - TOXIC SUBSTANCES CONTROL SUBCHAPTER I - CONTROL OF TOXIC SUBSTANCES Sec. 2605 - Regulation of hazardous chemical substances and mixtures. 15 U.S.C. §2605 (b)(1)(A).

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     There is no corresponding record for this reference.
103. 103

     United States Code, 2018 Edition, Supplement 5, Title 15 - COMMERCE AND TRADE. Title 15 - COMMERCE AND TRADE CHAPTER 53 - TOXIC SUBSTANCES CONTROL SUBCHAPTER I - CONTROL OF TOXIC SUBSTANCESec. 2625 – Administration. 15 U.S.C. § 2625 (c).

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104. 104

     U.S. Environmental Protection Agency (EPA). Cumulative Risk Assessment under the Toxic Substances Control Act. 2023. https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/cumulative-risk-assessment-under-toxic-substances (accessed 2023-06-06).

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105. 105

     Koustas, E.; Lam, J.; Sutton, P.; Johnson, P. I.; Atchley, D. S.; Sen, S.; Robinson, K. A.; Axelrad, D. A.; Woodruff, T. J. The Navigation Guide─Evidence-based medicine meets environmental health: Systematic review of nonhuman evidence for PFOA effects on fetal growth. Environ. Health Perspect 2014, 122 (10), 1015– 1027,  DOI: 10.1289/ehp.1307177

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     106

     The Navigation Guide - evidence-based medicine meets environmental health: systematic review of nonhuman evidence for PFOA effects on fetal growth

     Koustas Erica; Lam Juleen; Sutton Patrice; Johnson Paula I; Atchley Dylan S; Sen Saunak; Robinson Karen A; Axelrad Daniel A; Woodruff Tracey J

     Environmental health perspectives (2014), 122 (10), 1015-27 ISSN:.

     BACKGROUND: In contrast to current methods of expert-based narrative review, the Navigation Guide is a systematic and transparent method for synthesizing environmental health research from multiple evidence streams. The Navigation Guide was developed to effectively and efficiently translate the available scientific evidence into timely prevention-oriented action. OBJECTIVES: We applied the Navigation Guide systematic review method to answer the question "Does fetal developmental exposure to perfluorooctanoic acid (PFOA) or its salts affect fetal growth in animals ?" and to rate the strength of the experimental animal evidence. METHODS: We conducted a comprehensive search of the literature, applied prespecified criteria to the search results to identify relevant studies, extracted data from studies, obtained additional information from study authors, conducted meta-analyses, and rated the overall quality and strength of the evidence. RESULTS: Twenty-one studies met the inclusion criteria. From the meta-analysis of eight mouse gavage data sets, we estimated that exposure of pregnant mice to increasing concentrations of PFOA was associated with a change in mean pup birth weight of -0.023 g (95% CI: -0.029, -0.016) per 1-unit increase in dose (milligrams per kilogram body weight per day). The evidence, consisting of 15 mammalian and 6 nonmammalian studies, was rated as "moderate" and "low" quality, respectively. CONCLUSION: Based on this first application of the Navigation Guide methodology, we found sufficient evidence that fetal developmental exposure to PFOA reduces fetal growth in animals.

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106. 106

     Office of Environmental Health Hazard Assessment. Proposition 65: Evidence on the Carcinogenicity of Perfluorooctane Sulfonic Acid (PFOS) and Its Salts and Transformation and Degradation Precursors. 2021, p 65. https://oehha.ca.gov/media/downloads/crnr/pfoshid092421.pdf.

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107. 107

     Bachmanov, A. A.; Reed, D. R.; Beauchamp, G. K.; Tordoff, M. G. Food Intake, Water Intake, and Drinking Spout Side Preference of 28 Mouse Strains. Behavior Genetics. 2002, 32 (6), 435– 443,  DOI: 10.1023/A:1020884312053

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108. 108

     Akhtar, S.; Pranay, K.; Kumari, K. Personal protective equipment and micro-nano plastics: A review of an unavoidable interrelation for a global well-being hazard. Hygiene and Environmental Health Advances. 2023, 6, 100055  DOI: 10.1016/j.heha.2023.100055

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109. 109

     Zhang, Q.; Xu, E. G.; Li, J.; Chen, Q.; Ma, L.; Zeng, E. Y.; Shi, H. A Review of Microplastics in Table Salt, Drinking Water, and Air: Direct Human Exposure. Environ. Sci. Technol. 2020, 54 (7), 3740– 3751,  DOI: 10.1021/acs.est.9b04535

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     110

     A Review of Microplastics in Table Salt, Drinking Water, and Air: Direct Human Exposure

     Zhang, Qun; Xu, Elvis Genbo; Li, Jiana; Chen, Qiqing; Ma, Liping; Zeng, Eddy Y.; Shi, Huahong

     Environmental Science & Technology (2020), 54 (7), 3740-3751CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)

     A review. The ubiquity of microplastics in aquatic and terrestrial environments and related ecol. impacts have gained global attention. Microplastics have been detected in table salt, drinking water, and air, posing inevitable human exposure risk. However, rigorous anal. methods for detection and characterization of microplastics remain scarce. Knowledge about the potential adverse effects on human health via dietary and respiratory exposures is also limited. To address these issues, we reviewed 46 publications concerning abundances, potential sources, and anal. methods of microplastics in table salt, drinking water, and air. We also summarized probable translocation and accumulation pathways of microplastics within human body. Human body burdens of microplastics through table salt, drinking water, and inhalation were estd. to be (0-7.3)×104, (0-4.7)×103, and (0-3.0)×107 items per person per yr, resp. The intake of microplastics via inhalation, esp. via indoor air, was much higher than those via other exposure routes. Moreover, microplastics in the air impose threats to both respiratory and digestive systems through breathing and ingestion. Given the lifetime inevitable exposure to microplastics, we urgently call for a better understanding of the potential hazards of microplastics to human health.

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110. 110

     Yang, Q.; Dai, H.; Cheng, Y.; Wang, B.; Xu, J.; Zhang, Y.; Chen, Y.; Xu, F.; Ma, Q.; Lin, F.; Wang, C. Oral feeding of nanoplastics affects brain function of mice by inducing macrophage IL-1 signal in the intestine. Cell Rep. 2023, 42 (4), 112346,  DOI: 10.1016/j.celrep.2023.112346

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111. 111

     Liu, Q. Y.; Schauer, J. Airborne Microplastics from Waste as a Transmission Vector for COVID-19. Aerosol Air Qual. Res. 2021, 21 (1), 200439,  DOI: 10.4209/aaqr.2020.07.0439

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