Microand Nanoplastics and Human Health

In terms of human health risks, microplastics as contaminants in the wider environment represent a concern because it has been shown that they can be ingested by a wide range of aquatic organisms, both marine and freshwater, and thus have the potential to accumulate through the food chain. Aquatic organisms for which ingestion of microplastics has been documented in the field include those from across the marine food web, including turtles, seabirds, fish, crustaceans and worms (reviewed by Wright et al. 2013). Laboratory studies have confirmed that many other organisms have the capacity to ingest microplastics including zooplankton (Cole et al. 2013; Setälä et al. 2012). The majority of studies have documented microplastics in the guts of organisms, an organ that is not generally consumed directly by humans.

Exceptions to this include shellfish such as mussels, clams and some shrimps that are eaten whole or with their gut. The risk of ingesting microplastics contained within other tissues depends on the degree to which uptake of microplastics and translocation and redistribution and retention within other body tissues occurs. This concept is discussed further below, in relation to human ingestion.

In addition to the potential for ingestion to cause adverse biological effects due to gut blockages and/or damage, or the reduction in energy assimilation (Wright et al. 2013), the large surface area of microplastics means that environmental pollutants may sorb to the surface of the particles, with the potential to be transferred into body tissues once ingested. For a more comprehensive coverage of the uptake of microplastics by wildlife organisms, and the transfer to tissues of hydrophobic pollutants adsorbed from the surrounding environment, the reader is referred to excellent recent reviews (e.g. Engler 2012) and to other chapters in this issue (Koelmans 2015; Lusher 2015). Despite this concern, there is currently no available information to evidence the uptake or biological effects of microplastics originating from marine or terrestrial debris and subsequently ingested by humans through the food chain.

Ingestion of Microand Nanoplastics and Uptake Across the Gut

Whilst the potential clearly exists for microplastics to be present in food items, there is currently no evidence for the unintentional ingestion or subsequent translocation and uptake of microplastics into the human body through the diet. There is, however, a huge interest worldwide in the use of microand nanospheres as pharmaceutical drug delivery systems through oral, intravenous and transcutaneous routes (Kim et al. 2010), and in the migration of nanopolymers from packaging materials into food (EFSA 2011; Lagaron and Lopez-Rubio 2011). Based on these growing and fast moving fields, an enhanced understanding of the mechanistic pathways by which microand nanoparticles could enter the human body is starting to emerge, although many aspects of this field remain to be elucidated. Following oral ingestion, the gut mucosa represents an important barrier, which has evolved to allow efficient uptake of nutritious items, whilst excluding potentially harmful substances or organisms. Significant uptake of microplastics into the body through this route is in theory then limited to particles that can enter the body through exploitation of existing routes. Following oral ingestion, uptake of inert particles across the gut has been widely studied (O'Hagan 1996). The 'persorption' of starch particles as large as 150 μm through the tips of the villi was described in detail by Volkheimer (1977). According to his observations, persorption of particles can occur as a passive process in areas of the gut where the intestinal mucosa is covered by a single layer of epithelium. Persorbed particles were detectable in the lumen of blood and lymph vessels within minutes, and were eventually eliminated in the urine, confirming that the translocation of relatively large, inert particles from the gut to other body fluids is possible (Volkheimer 1977).

Aside from this observation, digestive absorption of smaller particles proceeds through pinocytosis and vesicular phagocytic processes for materials in the nano and micron range. Particle size is one of the most important factors in determining the extent and pathway of uptake. Smaller particles are generally favoured over larger ones. For example, polystyrene microspheres of 50–100 nm were more readily absorbed across the Peyer's patches and the villi of the gut than larger particles of 300–3000 nm (Jani et al. 1992; Florence and Hussain 2001). On the other hand, the uptake of ultrafine polylysine dendrimers of 2.5 nm was lower than that of larger polystyrene particles of 100 nm–3 µm, suggesting that size is not the only deciding factor (Florence et al. 2000). Indeed, a combination of size, surface charge and hydrophilicity all contribute to uptake affinity (as discussed by Awaad et al. 2012). The predominant site of uptake for micron-scale particles in the gut is reported to be through gut-associated lymphatic tissue (GALT), specifically by the Microfold (M) cells of the Peyer's patches. M cells are specialised epithelial cells that lack the microvilli found on other gut epithelial cells and instead have broader (micro)folds and a thinner luminal surface that allows them to actively take up particulate matter from the intestine. The reported efficiency of this uptake varies depending on the study method, species and particle type. Uptake of polystyrene microspheres through the gut by this route was higher in species such as rabbits, which have a high abundance of M cells (Pappo et al. 1989), and was enhanced when food was also present, probably due to the delayed transit time through the gut (Ebel 1990). As an alternative route, uptake by enterocytes appears to be limited to a size range of around 100 nm (Jani et al. 1992). Awaad et al. (2012) used fluorescent organosilica particles, histological examination and quantitative analysis to confirm an optimal size range of around 100 nm for uptake of particles through the M cells of the Peyer's patches, with smaller and larger particles less likely to be taken up. They also identified two alternative uptake pathways by which nanoparticles passed between (paracellular-E uptake) or through (transcellular-E uptake) enterocytes in the Peyer's patches. These two pathways have previously been described as major mechanisms for larger particles of >1 µm outside of the Peyer's patches (Kreuter 1991), but had not previously been described in relation to nanoparticle uptake by the Peyer's patches.

Garrett et al. (2012) used a novel bio-imaging technique, multimodal nonlinear optical microscopy, to document uptake of polymeric nanoparticles by enterocytes in the mouse gut in vivo. They studied a novel amphipathic polymer specifically designed for drug delivery, ammonium palmitoyl glycol chitosan (GCPQ) of 30–50 nm in diameter and showed that after uptake by enterocytes, particles accumulated at the base of the villi. From there, they passed into the blood stream and were transported to the liver, where they were detectable in the hepatocytes and intracellular spaces, before recirculating through the bile to the small intestine (Garrett et al. 2012) to be excreted with faecal matter. This is similar to previous results for larger micron-scale polystyrene and latex particles, suggesting that both micron and nano-scale polymers are treated in a similar manner (Jani et al. 1996), with uptake across the gut, recirculation and eventual elimination through faecal matter and urine (Fig. 13.1).

Fig. 13.1 A diagram illustrating a proposed recirculation pathway for polymer nanoparticles (ammonium palmitoyl glycol chitosan) after oral administration. The nanoparticles are taken up into the blood from the gut through M cells, and from there through the lymphatic system (shown in yellow) and into the liver and gall bladder. Particles are then re-released into the gut together with bile (shown in green) before excretion in faeces and urine. Adapted from Garrett et al. (2012)

This information is of high interest in terms of drug delivery, yet it also suggests that ample opportunity exists, following ingestion, for microand nanoplastics in food or water to enter, circulate and bioaccumulate within the body.

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