Repeated-oral dose toxicity of polyethylene microplastics and the possible implications on reproduction and development of the next generation
Introduction
Plastics, as synthetic or semi-synthetic polymers, were developed after the 19th-century Industrial Revolution and possess many useful characteristics, including light weight, low production costs, ease of manufacture and transport, and chemical resistance (Andrady and Neal, 2009). Thus, there are diverse applications for plastics, including packaging (such as containers and plastic bags), building products (such as plastic pipes or vinyl cladding), scientific components, and the aeronautics, electronics, transportation, and energy conservation sectors (Hopewell et al., 2009). Similarly, the use of plastics is continuously increasing, particularly as substitutes for materials such as paper, metals, wood, and glass, and the worldwide production of plastics reached 335 million tonnes per year in 2016 (PlasticsEurope, 2017).
Plastics are generally classified as either thermoplastic or thermosetting, based on their responses to high temperatures. Thermoplastics, including polyethylene (PE), polyvinyl chloride, polypropylene, acrylonitrile butadiene styrene, and nylon, can be reformed by heating without a change in chemical characteristics. Meanwhile, thermoset plastics, including epoxies, phenolics, silicones, and polyesters, have been mainly used in areas such as appliances and electronics owing to the enhanced chemical resistance, the heat stability, and the structural integrity. Thus, it has been expected that thermoplastics may be more degradable than thermoset plastics under environmental conditions and that the decomposition rate of plastics may be accelerated with increasing temperature in the atmosphere and oceans. Recent reports have suggested that pieces of plastic have been found in various species of organisms living in seas, rivers, lakes, and sediments (Santana et al., 2016; Pegado et al., 2018; Van Cauwenberghe and Janssen, 2014; Van Cauwenberghe et al., 2015; Fossi et al., 2012). Additionally, some researchers have reported microplastics in drinking water, sea salt, and canned fish (Oβmann et al., 2018; Mason et al., 2018; Kosuth et al., 2018; Karami et al., 2018). Thus, the adverse effects of microplastics on ecosystems and human health have been identified as potential global threats with ozone depletion and climate change (Thompson et al., 2009; Halden, 2010; Barboza et al., 2018). However, the available data regarding the toxicity of microplastics in humans are extremely limited.
PE has been incorporated into various household products, including cosmetics, toothpaste, and containers for food and dishwashing/laundry detergent. In 2015, PE accounted for approximately 32 % of worldwide plastic demand owing to its chemical, physical, and mechanical properties (www.committee.iso.org; Aggarwal and Sweeting, 1957). PE is primarily classified as a thermoplastic based on its low melting point. However, PE can be modified to form a thermoset plastic through processing, in which form it is not readily biodegraded under typical environmental conditions. In addition, microplastics are classified as either primary microplastics, which are less than 5 mm in size at the time of production, or secondary microplastics, which are split and shrunken to micro- or nano-sized particles in the environment. The physico-chemical properties of microplastics are currently presumed to be one of the key factors determining their toxicity and bioaccumulation, both of which vary greatly depending on the manufacturing process used to produce the plastic products and the degradation processes they encounter in the environment. Therefore, a safety assessment of primary microplastics with a relatively simple composition is an urgent need to understand the toxicity of secondary microplastics produced from plastic wastes under environmental conditions. Additionally, environmental pollutant-induced adverse health effects are generally caused by chronic exposure with relatively low dose, and effects on the reproduction and immune system are among the main concerns as consider effects of microplastics on human health (Jaikumar et al., 2019; Au et al., 2015; Veneman et al., 2017; Wright and Kelly, 2017). Therefore, in this study, we administered commercially available PE microplastics to mice by gavage for 90 days with reference to the related OECD test guideline (No. 422, Fig. 1). Then, we investigated the immunotoxic effects in parents, especially dams, and the offspring together with effects on the reproduction and development.
Section snippets
PE preparation and characterization
Surfaces of PE microplastics were modified to contain acid and hydroxy groups (Sigma-Aldrich, Cat No. 434272, 40−48 μm, melting point 144 °C, Darmstadt, Germany). A stock solution of PE microplastics (10 mg/mL) was well suspended in autoclaved drinking water and serially diluted prior to dosing. The morphology of the PE particles was investigated using scanning electron microscopy (SEM; CX-200, COXEM, Korea). Additionally, PE microplastics are easily incorporated into various chemicals, thus we
Properties of PE microplastics
The physicochemical properties of microplastics function as important factors determining the interaction with the biological system and subsequent toxic response. As shown in Fig. 2(A), the surface of PE microplastics was irregular. The size of the PE microplastics dispersed in drinking water was 16.9 ± 1.9 μm, and the particle number in a stock solution (10 mg/mL) was 2.27 ± 0.04 (X 106) particles/mL (data not shown). Additionally, the PE microplastics were not degraded in an artificial
Discussion
An EU report suggested that the service lifespan (from production to waste) of plastic products varies greatly, from less than 1 year to more than 50 years, in part because only some plastics are collected and recycled, however, all plastics ultimately became waste and accumulate in the environment. Given that plastic production continues to increase, there is growing global concern about environmental pollution caused by plastic waste. The US National Oceanic and Atmospheric Administration
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgement
This work was supported by a grant from Kyung Hee University in 2018 (20180872).
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These authors contributed equally to this work as first authors.