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VeilleNanos - Health risks of nanos in food

Health risks of nanos in food

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Health risks of nanos in food

By the AVICENN team – Last modification June 2024

Reasons for concern regarding the ingestion of nanos

Studies have shown that nanomaterials can:

Nanoparticles of titanium dioxide (E171)

The food additive E171, consisting of particles of titanium dioxide (TiO2) (some of which in nano form), has been banned in 2020 in France and 2022 in Europe because of potential genotoxic effects (DNA damage). In addition, numerous publications report harmful effects on health related to the ingestion of TiO2 nanoparticles: risks for the liver, ovaries and testicles in humans, immune problems and precancerous lesions in the colon in rats, disturbances of the intestinal microbiota, inflammations and alterations of the intestinal barrier in animals as well as in humans, harmful effects on offspring in rodents, etc.

At the end of 2022, Anses published its opinion on the risk assessment of the nanometric fraction of the food additive E171 which points out the lack of toxicological data available to perform a complete assessment of the additive E171 and recommends limiting the uses and exposures of workers and consumers to nanomaterials, “by promoting the use of safe products, free of manufactured nanomaterials, and by limiting these uses to those considered in fine as duly justified and subject to a documented demonstration of risk acceptability”.

→ For more information, check our data sheet Risks associated with the ingestion of titanium dioxide nanoparticles 

Silica nanoparticles (E551)

Potential adverse health effects associated with the ingestion of silica nanoparticles (SiO2 corresponds to the additive E551) have been highlighted for several years5See for example:
Molecular mechanisms of silica nanoparticle-induced cell transformation in Bhas cells 42, Anais Kirsch’s thesis, under the supervision of Hervé Schohn, Yves Guichard and Hélène Dubois-Pot Schneider, in preparation at the University of Lorraine, within the framework of Biology, Health, Environment, in partnership with the Centre de Recherche en Automatique de Nancy since May 12, 2017 : see the comic book and the video (both made in 2018)
Amorphous Silica Particles Relevant in Food Industry Influence Cellular Growth and Associated Signaling Pathways in Human Gastric Carcinoma Cells, Wittig A et al, Nanomaterials (Basel), 13;7(1), January 2017
Critical assessment of toxicological effects of ingested nanoparticles, McCracken C et al, Environ. Sci.: Nano, 3, 256-282, 2016
Critical review of the safety assessment of nano-structured silica additives in food, Winkler HC et al, Journal of Nanobiotechnology, 14:44, June 2016
Biodistribution, excretion, and toxicity of mesoporous silica nanoparticles after oral administration depend on their shape, Li L et al, Nanomedicine: Nanotechnology, Biology and Medicine, 11(8): 1915-1924, November 2015
Toxicity, genotoxicity and proinflammatory effects of amorphous nanosilica in the human intestinal Caco-2 cell line, Tarantini A et al, Toxicology in Vitro, 29(2): 398-407, March 2015
Novel insights into the risk assessment of the nanomaterial synthetic amorphous silica, additive E551, in food, van Kesteren PCE et al, Nanotoxicology, 2014
including dysfunction of cell division and disruption of cell traffic6See in particular:
-Evaluation of
the risks associated with nanomaterials for the general population and the environment, Afsset (now ANSES), March 2010
In vitro toxicity of amorphous silica nanoparticles in human colon carcinoma cells, Nanotoxicology, 7(3), May 2013
Presence of nanosilica (E551) in commercial food products: TNF-mediated oxidative stress and altered cell cycle progression in human lung fibroblast cells, Cell Biology and Toxicology, February 2014
Sub-chronic toxicity study in rats orally exposed to nanostructured silica, Particle and Fibre Toxicology, 11:8, 2014
as well as adverse effects on the liver7 See in particular:
Silica nanoparticle-induced toxicity in mouse lung and liver imaged by electron microscopy, Fundamental Toxicological Sciences, 2(1): 19-23, 2015
Novel insights into the risk assessment of the nanomaterial synthetic amorphous silica, additive E551, in food, van Kesteren PCE et al, Nanotoxicology, 2014
. This is worrying if we consider that we absorb on average about 124 mg of nano-silica (E551) per day8cf. silica nanoparticles in food, a risky diet, OMNT, 20 April 2011; the article in French is no longer accessible, but the source, in English, is still accessible: Presence and risks of nanosilica in food products, Dekkers et al, Nanotoxicology, 5(3): 393-405, 2011 . Moreover, some nanosilicas are more genotoxic at low doses than at high doses9See in particular:
– Results of the European program Nanogenotox on the genotoxicity of nanomaterials, presented in French at ANSES, during the Restitution of the national research program environment health work: Chemical substances and nanoparticles: models for the study of exposures and health effects: Participant file et Slide show, November 2013.
‘Facilitating the safety evaluation of manufactured nanomaterials by characterising their potential genotoxic hazard’, Nanogenotox, 2013 and RISKS: Lessons from the Nanogenotox research program, veillenanos.co.uk, December 2013
Papers presented at the meeting of the risk assessment and research office for the Netherlands Consumer Product Safety Authority (NVWA) in October 2013
.

Having found in vitro that silicon dioxide nanoparticles can generate inflammation in the gastrointestinal tract of mice (an attack on the immune defense of the digestive system), a team of Swiss researchers has advocated for less use of silica particles as a food additive10Cf. Food additives: better assessing the risk of nanoparticles, press release, 27 June 2017 ; In-vitro test to assess the risk of nanomaterials in food, Project led by Hanspeter Nägeli, Institute of Veterinary Pharmacy and Toxicology, University of Zurich (Switzerland) between 2012-2015 and National Research Program NRP 64 – Opportunities and Risks of Nanomaterials – Results, Conclusions and Perspectives – final brochure, Swiss National Science Foundation, March 2017 ; MyD88-dependent pro-interleukin-1B induction in dendritic cells exposed to food-grade synthetic amorphous silica, Winckler HC et al, Particle and Fibre Toxicology, 14:21, June 2017.

The re-evaluation of silica in the form of E551 (nano and non-nano), was adopted much later than the original schedule, at the end of 2017, without any definitive conclusions being drawn regarding the safety or toxicity of this additive. A call for data was opened by EFSA between October 2018 and May 2020. There will be no new call for additional data and if no in the absence of conclusive data can be obtained, the current authorization of this food additive would be revised on the basis of EFSA’s current scientific opinion and the additive could be withdrawn from the European Union’s list of authorized additives.

In the meantime, new disturbing studies have been published in scientific journals11See in particular:
Oral Toxicokinetics, Tissue Distribution, and 28-Day Oral Toxicity of Two Differently Manufactured Food Additive Silicon Dioxides, Yoo N-K et al, Int J Mol Sci, 5;23(7): 4023, April 2022
Gut microbiome and plasma metabolome changes in rats after oral gavage of nanoparticles: sensitive indicators of possible adverse health effects, Landsiede R et al, Particle and Fibre Toxicology, 19(21), 2022
Physiological and Behavioral Effects of SiO2 Nanoparticle Ingestion on Daphnia magna, Kim Y et al, Micromachines (Basel), 12(9): 1105, September 2021
Dietary nanoparticles alter the composition and function of the gut microbiota in mice at dose levels relevant for human exposure, Perez L et al, Food and Chemical Toxicology, 154, August 2021
Particles in food additives: what are the effects on digestive health? Focus on the ANR PAIPITO projectInterview with Marie Carrière (CEA Grenoble), Agence nationale de la recherche, June 7, 2021
Oral intake of silica nanoparticles exacerbates intestinal inflammation, Ogawa T et al, Biochemical and Biophysical Research Communications, 534(1): 540-546, January 2021
Impacts of foodborne inorganic nanoparticles on the gut microbiotaimmune axis: potential consequences for host health, Lamas B and Houdeau E, Particle and Fibre Toxicology, 17: 19, 2020
Hazard identification of pyrogenic synthetic amorphous silica (NM-203) after sub-chronic oral exposure in rat: a multitarget approach, Tassinari R et al, Food Chem Toxicol, 137: 111168, 2020
Toxicity to RAW264.7 Macrophages of Silica Nanoparticles and the E551 Food Additive, in Combination with Genotoxic Agents, Dussert F et al, Nanomaterials, MDPI, 10 (7): 1418, 2020: Silica nanoparticles are likely to carry genotoxic agents on their surface which leads to aggravate their adverse effects on DNA
Small silica nanoparticles transiently modulate the intestinal permeability by actin cytoskeleton disruption in both Caco-2 and Caco-2/HT29-MTX models, Cornu R et al, Arch Toxicol, 94(4): 1191-1202, April 2020
Chronic oral exposure to the food additive E551 (silica dioxide) blocks induction of oral tolerance and predisposes to food intolerance in mice, Breyner NM et al. Journées Francophones de Nutrition, November 2019
Chronic oral exposure to synthetic amorphous silica (NM-200) results in renal and liver lesions in mice, Boudard D et al, Kidney International Reports, 2019
Risk assessment of silica nanoparticles on liver injury in metabolic syndrome mice induced by fructose, Li J et al, Science of The Total Environment, 628-629: 366-374, July 2018: “Silica nanoparticles (SiNPs) aggravate liver injury in metabolic syndrome mice; SiNPs lead to mitochondrial injury in liver; SiNPs stimulate hepatic ROS generation; SiNPs lead to hepatic DNA damage”
Silicon dioxide nanoparticle exposure affects smallintestine function in an in vitro model, Guo Z et al, Nanotoxicology, April 2018: “SiO2 NP exposure significantly affected iron (Fe), zinc (Zn), glucose, and lipid nutrient absorption. Brush border membrane intestinal alkaline phosphatase (IAP) activity was increased in response to nano-SiO2. The barrier function of the intestinal epithelium (…) was significantly decreased in response to chronic exposure. Gene expression and oxidative stress formation analysis showed NP altered the expression levels of nutrient transport proteins, generated reactive oxygen species, and initiated pro-inflammatory signaling. SiO2 NP exposure damaged the brush border membrane by decreasing the number of intestinal microvilli, which decreased the surface area available for nutrient absorption. SiO2 NP exposure at physiologically relevant doses ultimately caused adverse outcomes in an in vitro model.
. These studies confirm the existence of harmful effects related to the ingestion of silica nanoparticles, particularly on the liver, intestines and kidneys or the immune system.

(Silica manufacturers have attempted to defend their product by attacking one of these studies, published in 2019; the researchers in question then responded, in the same journal, by dispelling one by one the criticisms put forward by the silica manufacturers12The original article was by Boudard D et al. : Chronic oral exposure to synthetic amorphous silica (NM-200) results in renal and liver lesions in mice, Boudard D et al, Kidney International Reports, 2019. The letter to the editor from representatives of silica manufacturers (or users) (the Association of Synthetic Amorphous Silica Producers (ASASP), PQ Corporation, Wacker Chemie AG, Evonik Resource Efficiency GmbH, Grace Europe Holding GmbH, Solvay, and Pittsburgh Plate Glass Company) was sent in November 2019. The researchers’ response was sent in December 2019. Both were published on the KI Reports website on March 10, 2020.).

In February 2024, French and Canadian researchers warned that silica nanoparticles could promote gluten13Cf. Evaluating the Effects of Chronic Oral Exposure to the Food Additive Silicon Dioxide on Oral Tolerance Induction and Food Sensitivities in Mice, Lamas B. et al., Environmental Health Perspectives, 132, 2, 2024, DOI : 10.1289/EHP12758.

Silver nanoparticles (E174)

Silver nanoparticles are present in the additive E174 but also in antibacterial food packaging or containers; silver nanoparticles injected into the blood of rats have been found in the liver, in the nucleus of hepatocytes, and alter the cells of this vital organ14Cf. Effects of Silver Nanoparticles on the Liver and Hepatocytes in vitro, Gaiser B.K. et al, Toxicol. Sci., 2012.

Another study showed that silver nanoparticles administered orally to mice have damaged the epithelial cells and the intestinal glands of rodents and resulted in a decrease in their weight15cf. Toxic effects of repeated oral exposure of silver nanoparticles on small intestine mucosa of mice, Toxicology Mechanisms and Methods, 23(3), March 2013 ;. A disruption of the intestinal flora has also been observed in zebrafish and mice16Cf. Ingestion of metal-nanoparticle contaminated food disrupts endogenous microbiota in zebrafish (Danio rerio), Environmental Pollution, 174, March 2013as well as in mice17Dietary silver nanoparticles can disturb the gut microbiota in mice, Van den Brule S et al, Particle and fibre toxicology, 13, 2016 (see abstract and analysis in French here: Effects of silver nanoparticles on bacterial communities, Vernis L., Science Watch Bulletin, n°32, October 2017) fed with food containing silver nanoparticles.

It has also been shown that the ingestion of silver nanoparticles causes permanent alterations in the genome in mice and could therefore lead to cancer18Oral ingestion of silver nanoparticles induces genomic instability and DNA damage in multiple tissues, Nanotoxicology, 2014
See also Exposure to silver nanoparticles induces size- and dose-dependent oxidative stress and cytotoxicity in human colon carcinoma cells, Toxicology in Vitro, 28(7), 1280-1289, October 2014
, etc. Other concordant results have been published recently, also showing harmful effects of silver nanoparticles on the kidneys of rats19See for example:
Oral subchronic exposure to silver nanoparticles causes renal damage through apoptotic impairment and necrotic cell death, Rui Deng et al, Nanotoxicology, 11(5): 671-686, 2017
Comparative toxicity of silicon dioxide, silver and iron oxide nanoparticles after repeated oral administration to rats, Journal of Applied Toxicology, 35(6): 681-693, June 2015
.

Gold nanoparticles (E175)

In 2023, French scientists have shown, in E175-exposed femal mice, gut microbiota alterations likely to promote the worsening of metabolic disorders, for example, under an unbalanced diet. They recommend the establishment of toxic reference values for the safe use of gold as food additive (E175) in the human diet20Cf. A 90-day oral exposure to food-grade gold at relevant human doses impacts the gut microbiota and the local immune system in a sex-dependent manner in mice, Evariste L et al., P&FT, 20(27), juillet 2023.

Zinc oxide (ZnO) nanoparticles

Zinc oxide nanoparticles present on the lining of cans get into the food inside and may lead to poorer nutrient absorption and increased permeability of the gut, transferring unwanted compounds into the bloodstream21See in particular:
ZnO nanoparticles affect intestinal function in an in vitro modelMoreno-Olivas F et al, Food Funct., 9: 1475-1491, 2018; see French abstract here : Canned foods could be harmful to our digestion, Top Health, April 10, 2018 and here canned foods interfere with digestion,Bio on the Front Page, April 12, 2018.
.

Cerium dioxide (CeO2) nanocomposites

They can cause an alteration of the metabolism22Cf. “Oxide nanoparticles: what toxicity on intestinal cells?”, work of the CEA-iBEB carried out within the framework of the ANR project AgingNanoTroph, January 3, 2013.

Nano cellulose

In addition to the health repercussions of nanoparticle ingestion, it should be noted that the environmental risks are also poorly understood and a cause for concern.

Many scientific uncertainties

Much is still unknown today about the impact that ingestion of nanomaterials can have on human health. Oral toxicity studies of nanoparticles are rare and many may have had methodological weaknesses that make their results difficult to use . Experimental conditions still poorly reflect how consumers are actually exposed. The nanomaterials considered are often synthesized in the laboratory and thus different from the nanomaterials (and nanomaterial residues) that consumers actually ingest. In addition, the physicochemical characteristics of the tested nanoparticles and their interactions with the food matrix are insufficiently documented. Nevertheless, progress has recently been made, thanks to improvements in researchers’ practices, tools and protocols.

The complexity of assessing the risks associated with the ingestion of nanomaterials

One of the problems that is likely to remain, however, is the great complexity of assessing the risks associated with the ingestion of nanomaterials: the toxicity of nanoparticles differs according to their physicochemical characteristics (size, shape, degree of agglomeration, etc.). However, these characteristics vary greatly from one nanomaterial to another and can change throughout their life cycle:

  • depending on the conditions under which the nanomaterials are synthesized, stored, and possibly coated
  • by the transformations they undergo during cooking and preparation of dishes or in the digestive system23Mammalian gastrointestinal tract parameters modulating the integrity, surface properties, and absorption of food-relevant nanomaterials, Bellmann S et al, WIREs Nanomed Nanobiotechnol, 2015 (e.g. contact with the acidic environment of the stomach, etc.)
  • during interactions with packaging and/or with other ingredients and chemical substances with which nanomaterials are mixed (before and during ingestion and digestion); for example, a “cocktail effect” with certain other synthetic molecules could occur24Could nanomaterials, combined with other substances, become (more) dangerous? Toxicologists often work by isolating substances, which does not allow them to establish the interaction effects of a plurality of substances entering the body.

In addition, the risk assessment should consider:

Since 2009, there has been a broad consensus on the need to strengthen research on the risks associated with ingested nanos

In 2009, the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) convened an expert meeting on the food safety implications of nanotechnology: the report which was published in 2011, lists the research needed to better assess risks in this field.

Since 2009, ANSES has been calling for improved knowledge about the hazards and consumer exposure to nanomaterials. In October 2016, ANSES was asked by its supervisory ministries to study the risks associated with nanoparticles in food, and more specifically:

  • to carry out a detailed study of the agri-food sector with regard to the use of nanos in food
  • to prioritize the substances and/or end products of interest according to relevant criteria determined during the expertise
  • to review the available data (toxicological effects and exposure data)
  • and depending on availability, to study the feasibility of a health risk assessment for certain products.

A “working group” (“WG nano food”) composed of independent experts was set up during 2017. The first results of the expertise, initially expected by the end of 201728Response to question No. 85181 by Deputy Yves Daniel, Ministry of Social Affairs, Health and Women’s Rights, October 2016; see also. Anses calls for applications from scientific experts to form a working group (WG) “Nanos & Food”, ANSES, January 2017, was published mid-2020 in a report identifying food products that contain (or may contain) nanomaterials29Cf. ANSES, Nanomaterials in food products; collective expertise report, May 2020.
In 2021, ANSES published a second report: a specific guide to assess the health risks of nanomaterials in food that complements the report on the same subject published a few months earlier by EFSA.

At the end of 2022, Anses published its opinion and report on the risk assessment of the nanometric fraction of the food additive E171 which points out the lack of toxicological data available to perform a complete assessment of the additive E171 and recommends limiting the uses and exposures of workers and consumers to nanomaterials, “by promoting the use of safe products, free of manufactured nanomaterials, and by limiting these uses to those considered in fine as duly justified and subject to a documented demonstration of risk acceptability”.

Notwithstanding the broad consensus on the need to strengthen research on the risks of ingested nanomaterials, research is still limited.

Pending conclusive evaluations, marketing of food products containing nanoparticles continues

In the meantime, consumers continue to ingest nanoparticles of titanium dioxide, silica, silver, etc., most often without knowing it, due to the lack of enforcement of the labeling obligation by the industry.

In presenting its risk assessment guide for nanos in food (2021) as well as its opinion and report on the risk assessment of the nanometric fraction of the food additive E171 (2022), Anses reiterated “the need to limit the exposure of workers, consumers and the environment to nanomaterials” and recommended “to favor safe products, free of these substances”.

Certainly, the additive E171 containing nanoparticles of titanium dioxide has been banned in food in France in 2020 and in the European Union in 2022, but it remains authorized for the moment in medicines and cosmetics (despite the fact that in toothpastes or lipsticks and balms for example, it is likely to be ingested).

In the light of these dangers, calls for caution and the precautionary principle

Recommendations of public authorities on nanos in food

Faced with the numerous uncertainties concerning the risks of nanos in food, many public or para-public organizations have issued recommendations concerning the use of nanomaterials or nanotechnologies in the food sector30See in particular the numerous government reports listed in our bibliography. Among the most comprehensive reports is theOpinion on the ethical issues of nanotechnologies in the agri-food sector of the Commission de l’éthique en science et en technologie du Québec published as early as 2011, with nine concrete recommendations that provide a good overview of recommendations issued by various actors in other settings, with the advantage of being relatively well articulated and almost exhaustive here..

These recommendations can be summarized as follows:

  • to carry out a scientific and technological watch on nanotechnological applications in the agri-food industry and the associated risks;
  • to carry out further research on risks
  • to inform the public
  • to consult the population
  • to develop an interdepartmental exchange of information on the state of scientific knowledge on risks
  • to allow public evaluation of the safety and legal framework of the products concerned
  • to demand transparency from manufacturers and labeling of the products concerned.

NGOs have been calling for a moratorium on nanos in food for years

Among the NGOs that have spoken out against the use of nanomaterials in everyday consumer products31See among the 51 stakeholder papers from organizations that took a position during the 2009-2010 national public debate on nanotechnology., various NGOs32See in particular the NGO reports listed in our bibliography have specifically called for a moratorium on the use of nanomaterials in food, including:

Consumers unwilling to be guinea pigs

In a general context where consumers are increasingly suspicious of industrial food34See for example Alimentation : face aux doutes, les internautes s’organisent, Le Monde, April 15, 2013, the reluctance and distrust of consumers towards nanoparticles in food are growing. In general, consumers expect more transparency and do not want to be “guinea pigs” for nano-food35“Nanotechnologies: all guinea pigs of nano-food?“, Basta!, January 14, 2010. However, they are already, unwillingly, since our food already contains nanomaterials – and not only “virtual” nano objects like those used at INRA for the above-mentioned study conducted in 2011.

Since 2016, the petition “Stop nanoparticles on our plates!” launched by Agir pour l’Environnement, demanding a moratorium on nanoparticles in common food products, has gathered more than 52,000 signatures.

In 2011, INRA researchers concluded that “in situations of uncertainty and controversy, decision-makers should pay particular attention to participatory or deliberative modes of communication”. In this respect, the association Sciences Citoyennes has been campaigning for several years for the setting up of citizens’ conventions whose recommendations should be taken into account by the authorities.

The INRA researchers add that “this communication must be accompanied by a strong policy guaranteeing the safety of nanofoods in a context of mistrust among European consumers“. It remains to be seen who should bear the cost of such a safety policy aimed at reassuring the population about applications whose advantages have yet to be proven and from which the agri-food industry and certain research laboratories seem to be the main beneficiaries: should taxpayers pay or should it be companies hoping to profit from their sales ?

Any questions or comments? This information sheet compiled by AVICENN is intended to be completed and updated. Please feel free to contribute.

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Information sheet initially created in May 2013


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