This article shows that the impact of nano- and microplastics on human health is still largely unknown. Follow-up research is therefore needed because for decades, people have come into contact with the small plastic particles in their living environment via the air, water and food. These small particles vary in size from nanometres to micrometres.

Microplastic, finger

Health damage in people and animals

It has already become clear that these particles, albeit at high concentrations, can cause health damage (toxicity of particles) in animals. Furthermore, these particles might introduce harmful chemical substances or pathogens into the body.

Within the ZonMw programme Microplastics & Health the effects of microplastics on human health have been explored in 15 projects. All of the projects started in 2019 and the initial results are now known. Experimental human material or laboratory animals were exposed to micro- and nanoplastics. This revealed that small plastic particles can pass through the intestinal wall, lungs, placenta and even the blood-brain barrier. They also appear to disrupt the functioning of the different body cells of these organs. In some instances, inflammatory responses occur too.

Reduced gastrointestinal function

Plastic particles can enter the body and come into contact with the intestines via the food chain, for example when people eat fish and shellfish. For a long time, the effect on our intestinal health remained unclear, but now the first results are emerging. Short-term exposure to plastic particles between 1 and 10 µm in size can cause a decrease in the functioning of the large intestine. Sometimes, the particles influenced the viability of the cells and the permeability (tested on human and pig cells) too, but only at high concentrations. The plastics HDPE and nylon were also found to cause a decrease in the barrier function of the intestines. As a result of this, the permeability of the cells increased.

The plastic polystyrene was likewise capable of doing this and could be seen inside the intestines within just 5 hours of exposure. About 6% of the tested particles were absorbed by the intestines. Particles of 10 µm passed through the intestinal membrane easiest due to the large influence they exerted on the permeability of the intestine.

Chemical substances in the intestine

Ingesting food increases the exposure of our intestines to micro- and nanoplastics. That can cause chemical substances to be released, such as softening agents and flame retardants, which can also become part of our food via packaging material. No less than 183 such chemicals were present in microplastic litter on the beach.

The latest results from the intestines projects reveal that these chemicals, which adhere to the microplastics, can pass through the intestinal wall. This concerns potentially toxic organic compounds, such as persistent organic pollutants that are produced by humans. These substances, in addition to metals, were found on microplastics on the beach. About 22 chemicals could pass through the intestinal epithelium when these were tested in a cell culture model. Some reached the innermost part of the intestines, and others reached organs of the gastrointestinal tract.

Altogether 18 of the above-mentioned 22 chemicals influenced molecular and cellular processes in such a manner that undesirable pathways were initiated that could give rise to a disrupted tissue function and/or hormone balance. On a side note, exposure in humans was not included in this experiment, and so it is not clear whether the tested amounts of microplastics in the gastrointestinal model provide a realistic outcome. The exposed quantities might, in reality, be lower, but that exposure is chronic.

Inflammatory responses

In the blood, the macrophages (a certain type of immune cell that normally engulfs pathogens) become extra active in response to microplastics. This means that inflammatory responses could occur. Due to the presence of microplastics in the intestines, inflammatory proteins were also activated. However, that was not always the case because that depended on the type of plastic tested. Polystyrene, in particular, was found to activate inflammatory proteins, for example. In addition, certain immune cells from the adaptive immune system are extra active in response to polystyrene. Researchers noticed that ‘weathered’ plastic particles damaged by UV radiation and surface water caused a larger response from body cells.

Disrupted lung function

The lungs also experience negative influences from the presence of microplastics. In the lungs, almost 4% of a high concentration of polystyrene nanoplastics passed through the tissue. This type of plastic could already be seen in the lungs within 24 hours. A moderate inflammatory response was observed in the lungs as well.

As the high exposure of textile workers to microplastic fibres has been correlated with the development of lung diseases, the effect of polyester and nylon fibres on the lungs was investigated too. That took place in two simulated mini lungs. Lung epithelial tissue from both mice and humans was investigated. Particles of 15 and 10 µm were taken up by the respiratory passages. The smallest particles of 5 µm even reached the lung vesicles at the end of the bronchioles. The result was that the mini lungs grew less well or repaired less well after damage.

Harmful chemicals from nylon fibres

Nylon fibres, in particular, inhibited the growth of the lungs. The next question was whether this inhibition was the consequence of the nylon fibres or the chemicals leaching  from these. Chemicals that leach from the fibres were found to inhibit the growth. Further, as previously stated, a moderate inflammatory response was observed in the presence of nylon fibres. Nylon therefore directly affects the development of the mini lungs, a result that deserves further research.

Encapsulation by immune cells

The immune system also responds to microplastics. Immune cells view microplastics as foreign particles. In consequence, they respond to these in the same way as they would to pathogens: certain immune cells encapsulate particles to break them down. However, the researchers discovered that they only do that if they are surrounded by blood proteins. If not, the immune cells leave the particles alone.

The effect of exposure to microplastics via the skin was likewise investigated. Immune cells in the skin become active and respond mainly to weathered plastic particles, which are particles damaged by UV radiation and surface water. Subsequently, they activate the attackers of the immune system, the T-cells, which initiate a range of inflammatory responses. The size of the particles does not particularly matter: the immune cells devoured particles of variable sizes. The smallest particles did, nevertheless, cause the strongest response.

Allergic reaction

Further, it has become clear that dendritic cells, certain first-line immune cells active in mainly the skin, responded more strongly as soon as they came into contact again with plastic particles. This points to the development of an allergy to microplastics: the researchers do not exclude the possibility that this could arise after repeated exposure to plastics.

In follow-up research, multiple microorganisms and their microbial components such as lipopolysaccharides (LPS) and endotoxins should be tested. It is also important to test the response of the immune system after plastic ingestion in the case of intestinal diseases such as inflammatory bowel disease (IBD).

Ocean plastic and the immune system

The response of the immune system depends on the type of plastic and whether or not this is weathered. That was revealed by research in which use was made of plastics collected in the ocean and on the coast, which were ground into a range of microplastics in the lab. Four different types of plastics were investigated with a size of between 20 and 200 µm. The chemical composition, the number of particles and the particle size determine how vigorously immune cells respond. The most recent results reveal that the smallest particles, from 20 to 50 µm, most strongly stimulate the cell-killing effect of the immune system. In the follow-up research, the scientists want to test more inflammatory substances and measure the immune cells’ response to particles that possibly contain pathogens.

Inhibition of brain enzyme

Experiments with rodents and brain cell cultures revealed that nanoplastics can reach the brain and also pass through the blood-brain barrier. There they even influence the communication between immune cells: they inhibit an important enzyme that is necessary for the communication between brain cells. The further effect on the functioning of the brain is limited, or has not yet been demonstrated due to the short duration of the experiment. For this reason, follow-up research into the long-term effects of nanoplastics on the brain is necessary.

Plastic particles in human blood, placenta and amniotic fluid

The researchers are still examining whether and to what extent plastic particles are present in the human placenta, amniotic fluid and blood. As only a few samples have been tested, the researchers are cautious about drawing the conclusion that plastic particles are present (in measurable concentrations) in the blood circulation and foetal environment. However, the uptake of smaller microplastics and nanoplastics by placenta cells has been demonstrated in a laboratory setting.

Damage to placenta cells

In vitro experiments were carried out with a human placenta cell model. After just 1 to 2 hours, microplastics were visible in the placenta and especially the smallest particles were quickly absorbed by the placenta cells. Both the particles and any chemicals leaching out of these can cause damage to the foetal environment.

It was likewise demonstrated that the expression of a specific gene changed under the influence of pristine or clean microplastics. That gene codes for a protein that plays a role in female hormone production. The implications of this still need to be further investigated. Researchers will also further examine the different types of weathered and clean microplastics and their uptake and transport in the placenta. Possible hormone disruptions and the effect on the immune system will be included in this study.

Pathogens on microplastics

In surface water, microplastics are also a good carrier of pathogens such as bacteria. These pathogens adhere to microplastics in the water, can be transported over large distances and form a danger to public health. The River Rhine was sampled at both the coast and the German border to investigate this. Different plastics were collected with more than 200,000 particles per m3 of water. Potential pathogens and plastic decomposing bacteria were found on these particles.

In another project, microplastics were exposed to water that came from a wastewater treatment plant. The plastics were found to be microbiologically contaminated, which could be seen from the presence of the many genes that render bacteria resistant to antibiotics. Particles in these dirty environments had more resistance genes than particles collected at clean locations. Also, particles to which microorganisms from the environment adhered elicited a strong immune response. From all particles tested, the most contaminated particles originated from the environment. Particles with biofilms - that contained algae and potential pathogens – gave a stronger immune response in the tested cell culture model. For particles of 10 and 90 µm a strong immune response was observed, but this was not the case for a far smaller particle size of 1 µm. Follow-up research is needed with a controlled exposure in the lab for a fixed period of time. It is likewise necessary to further test exposure to different particles and the pathogens these carry from the environment.

Worrying results

In short, these initial results of the effect of micro-and nanoplastics in the body indicate how urgent and relevant further research is. In many cases, it is still difficult to translate the results to people. That is mainly because a good risk assessment does not exist yet. Toxicologists are working on a risk assessment model so that the risk of plastic intake via food, air or water can be precisely analysed. Nevertheless, despite the fact that there is still a lot of uncertainty in the interpretation of the initial laboratory results, the outcomes are worrying. That is also due to the fact that the amount of small particles in the living environment continues to increase. And because, for example, research into particulate matter, which contains plastic particles, reveals that small particles enter our body and can lead to health effects there.

It is clear that nano- and microplastics can undoubtedly have a negative influence on human health, but to what extent and in which situations that applies is difficult to establish because the risk assessment is still missing. The breakthrough projects will be continued in the new public-private consortium MOMENTUM. However, further follow-up research is necessary to make the actual health risks and possible solutions more tangible. The results included in this article are those that the researchers presented during the symposium organised by MOMENTUM and ZonMw on 4 November 2021. You can read more about the research in our webpage about the health effects of microplastics.

Would you like to receive more information about microplastics and health? Then please contact us via MicroplasticsHealth@zonmw.nl.

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