Hans J.P. Marvin

Review of health safety aspects of nanotechnologies in food production.

Due to new, previously unknown, properties attributed to engineered nanoparticles many new products are introduced in the agro-food area. Nanotechnologies cover many aspects, such as disease treatment, food security, new materials for pathogen detection, packaging materials and delivery systems. As with most new and evolving technologies, potential benefits are emphasized, while little is known on safety of the application of nanotechnologies in the agro-food sector. This review gives an overview of scientific issues that need to be addressed with priority in order to improve the risk assessment for nanoparticles in food. The following research topics are considered to contribute pivotally to risk assessment of nanotechnologies and nanoparticles in food products. Set a definition for NPs to facilitate regulatory discussions, prioritization of research and exchange of study results. Develop analytical tools for the characterization of nanoparticles in complex biological matrices like food. Establish relevant dose metrics for nanoparticles used for both interpretation of scientific studies as well as regulatory frameworks. Search for deviant behavior (kinetics) and novel effects (toxicity) of nanoparticles and assess the validity of currently used test systems following oral exposure. Estimate the consumer exposure to nanoparticles.

Distribution, elimination, and toxicity of silver nanoparticles and silver ions in rats after 28-day oral exposure.

We report the results of a 28-day oral exposure study in rats, exposed to <20 nm noncoated, or <15 nm PVP-coated silver nanoparticles ([Ag] = 90 mg/kg body weight (bw)), or AgNO(3) ([Ag] = 9 mg/kg bw), or carrier solution only. Dissection was performed at day 29, and after a wash-out period of 1 or 8 weeks. Silver was present in all examined organs with the highest levels in the liver and spleen for all silver treatments. Silver concentrations in the organs were highly correlated to the amount of Ag(+) in the silver nanoparticle suspension, indicating that mainly Ag(+), and to a much lesser extent silver nanoparticles, passed the intestines in the silver nanoparticle exposed rats. In all groups silver was cleared from most organs after 8 weeks postdosing, but remarkably not from the brain and testis. Using single particle inductively coupled plasma mass spectrometry, silver nanoparticles were detected in silver nanoparticle exposed rats, but, remarkably also in AgNO(3) exposed rats, hereby demonstrating the formation of nanoparticles from Ag(+)in vivo that are probably composed of silver salts. Biochemical markers and antibody levels in blood, lymphocyte proliferation and cytokine release, and NK-cell activity did not reveal hepatotoxicity or immunotoxicity of the silver exposure. In conclusion, oral exposure to silver nanoparticles appears to be very similar to exposure to silver salts. However, the consequences of in vivo formation of silver nanoparticles, and of the long retention of silver in brain and testis should be considered in a risk assessment of silver nanoparticles.

Climate change and food safety: An emerging issue with special focus on Europe

According to general consensus, the global climate is changing, which may also affect agricultural and livestock production. The potential impact of climate change on food security is a widely debated and investigated issue. Nonetheless, the specific impact on safety of food and feed for consumers has remained a less studied topic. This review therefore identifies the various food safety issues that are likely to be affected by changes in climate, particularly in Europe. Amongst the issues identified are mycotoxins formed on plant products in the field or during storage; residues of pesticides in plant products affected by changes in pest pressure; trace elements and/or heavy metals in plant products depending on changes in their abundance and availability in soils; polycyclic aromatic hydrocarbons in foods following changes in long-range atmospheric transport and deposition into the environment; marine biotoxins in seafood following production of phycotoxins by harmful algal blooms; and the presence of pathogenic bacteria in foods following more frequent extreme weather conditions, such as flooding and heat waves. Research topics that are amenable to further research are highlighted.

Presence of Nano-Sized Silica during In Vitro Digestion of Foods Containing Silica as a Food Additive

The presence, dissolution, agglomeration state, and release of materials in the nano-size range from food containing engineered nanoparticles during human digestion is a key question for the safety assessment of these materials. We used an in vitro model to mimic the human digestion. Food products subjected to in vitro digestion included (i) hot water, (ii) coffee with powdered creamer, (iii) instant soup, and (iv) pancake which either contained silica as the food additive E551, or to which a form of synthetic amorphous silica or 32 nm SiO(2) particles were added. The results showed that, in the mouth stage of the digestion, nano-sized silica particles with a size range of 5-50 and 50-500 nm were present in food products containing E551 or added synthetic amorphous silica. However, during the successive gastric digestion stage, this nano-sized silica was no longer present for the food matrices coffee and instant soup, while low amounts were found for pancakes. Additional experiments showed that the absence of nano-sized silica in the gastric stage can be contributed to an effect of low pH combined with high electrolyte concentrations in the gastric digestion stage. Large silica agglomerates are formed under these conditions as determined by DLS and SEM experiments and explained theoretically by the extended DLVO theory. Importantly, in the subsequent intestinal digestion stage, the nano-sized silica particles reappeared again, even in amounts higher than in the saliva (mouth) digestion stage. These findings suggest that, upon consumption of foods containing E551, the gut epithelium is most likely exposed to nano-sized silica.

Characterization of Translocation of Silver Nanoparticles and Effects on Whole-Genome Gene Expression Using an In Vitro Intestinal Epithelium Coculture Model

Applications of nanoparticles in the food sector are eminent. Silver nanoparticles are among the most frequently used, making consumer exposure to silver nanoparticles inevitable. Information about uptake through the intestines and possible toxic effects of silver nanoparticles is therefore very important but still lacking. In the present study, we used an in vitro model for the human intestinal epithelium consisting of Caco-2 and M-cells to study the passage of silver nanoparticles and their ionic equivalents and to assess their effects on whole-genome mRNA expression. This in vitro intestine model was exposed to four sizes of silver nanoparticles for 4 h. Exposure to silver ions was included as a control since 6-17% of the silver nanoparticles were found to be dissociated into silver ions. The amount of silver ions that passed the Caco-2 cell barrier was equal for the silver ion and nanoparticle exposures. The nanoparticles induced clear changes in gene expression in a range of stress responses including oxidative stress, endoplasmatic stress response, and apoptosis. The gene expression response to silver nanoparticles, however, was very similar to that of AgNO(3). Therefore, the observed effects of the silver nanoparticles are likely exerted by the silver ions that are released from the nanoparticles.

Minimal analytical characterization of engineered nanomaterials needed for hazard assessment in biological matrices

Abstract This paper presents the outcomes from a workshop of the European Network on the Health and Environmental Impact of Nanomaterials (NanoImpactNet). During the workshop, 45 experts in the field of safety assessment of engineered nanomaterials addressed the need to systematically study sets of engineered nanomaterials with specific metrics to generate a data set which would allow the establishment of dose-response relations. The group concluded that international cooperation and worldwide standardization of terminology, reference materials and protocols are needed to make progress in establishing lists of essential metrics. High quality data necessitates the development of harmonized study approaches and adequate reporting of data. Priority metrics can only be based on well-characterized dose-response relations derived from the systematic study of the bio-kinetics and bio-interactions of nanomaterials at both organism and (sub)-cellular levels. In addition, increased effort is needed to develop and validate analytical methods to determine these metrics in a complex matrix.

Characterization of Titanium Dioxide Nanoparticles in Food Products: Analytical Methods To Define Nanoparticles

Titanium dioxide (TiO2) is a common food additive used to enhance the white color, brightness, and sometimes flavor of a variety of food products. In this study 7 food grade TiO2 materials (E171), 24 food products, and 3 personal care products were investigated for their TiO2 content and the number-based size distribution of TiO2 particles present in these products. Three principally different methods have been used to determine the number-based size distribution of TiO2 particles: electron microscopy, asymmetric flow field-flow fractionation combined with inductively coupled mass spectrometry, and single-particle inductively coupled mass spectrometry. The results show that all E171 materials have similar size distributions with primary particle sizes in the range of 60-300 nm. Depending on the analytical method used, 10-15% of the particles in these materials had sizes below 100 nm. In 24 of the 27 foods and personal care products detectable amounts of titanium were found ranging from 0.02 to 9.0 mg TiO2/g product. The number-based size distributions for TiO2 particles in the food and personal care products showed that 5-10% of the particles in these products had sizes below 100 nm, comparable to that found in the E171 materials. Comparable size distributions were found using the three principally different analytical methods. Although the applied methods are considered state of the art, they showed practical size limits for TiO2 particles in the range of 20-50 nm, which may introduce a significant bias in the size distribution because particles <20 nm are excluded. This shows the inability of current state of the art methods to support the European Union recommendation for the definition of nanomaterials.

GMDD: a database of GMO detection methods

BackgroundSince more than one hundred events of genetically modified organisms (GMOs) have been developed and approved for commercialization in global area, the GMO analysis methods are essential for the enforcement of GMO labelling regulations. Protein and nucleic acid-based detection techniques have been developed and utilized for GMOs identification and quantification. However, the information for harmonization and standardization of GMO analysis methods at global level is needed.ResultsGMO Detection method Database (GMDD) has collected almost all the previous developed and reported GMOs detection methods, which have been grouped by different strategies (screen-, gene-, construct-, and event-specific), and also provide a user-friendly search service of the detection methods by GMO event name, exogenous gene, or protein information, etc. In this database, users can obtain the sequences of exogenous integration, which will facilitate PCR primers and probes design. Also the information on endogenous genes, certified reference materials, reference molecules, and the validation status of developed methods is included in this database. Furthermore, registered users can also submit new detection methods and sequences to this database, and the newly submitted information will be released soon after being checked.ConclusionGMDD contains comprehensive information of GMO detection methods. The database will make the GMOs analysis much easier.

Identification of potentially emerging food safety issues by analysis of reports published by the European Community’s Rapid Alert System for Food and Feed (RASFF) during a four-year period

The SAFE FOODS project undertakes to design a new approach towards the early identification of emerging food safety hazards. This study explored the utility of notifications filed through RASFF, the European Commissions Rapid Alert System for Food and Feed, to identify emerging trends in food safety issues. RASFF information and alert notifications published in the four-year period of July 2003-June 2007 were assigned to categories of products and hazards. For chronological trend analysis, a basic time unit of three months was chosen. Data within each hazard category were analyzed for chronological trends, relationships between product and hazard categories, regions of origin, and countries filing the notifications. Conspicuous trends that were observed included a rise in the incidence of food contact substances, particularly 2-isopropyl-thioxanthone, as well as of chemical substances migrating from utensils and fraud-related issues. Temporary increases were noted in the incidences of the unauthorized dye Para Red, genetically modified organisms, the pesticide isophenfos-methyl, and herring worm, Anisakis simplex. National and European authorities themselves have signaled these conspicuous trends and taken measures. It is recommended to add complementary data to RASFF data, including safety assessments, risk management measures, background data on hazards and surveillance patterns, for a holistic approach towards early identification of emerging hazards.

Single particle ICP-MS combined with a data evaluation tool as a routine technique for the analysis of nanoparticles in complex matrices

Detection and characterization of nanoparticles (NPs) in complex media as consumer products, food and toxicological test media is an essential part of understanding the potential benefits and risks of the application of nanoparticles. Single particle ICP-MS (spICP-MS) was studied as a screening tool for the detection and characterization of nanoparticles in complex matrices such as food and biological tissues. A data evaluation tool was created for the calculation of particle size, concentration and size distribution from the raw data. spICP-MS measurements were carried out on a standard quadrupole instrument as well as on a sector-field instrument. Performance characteristics were determined for four types of NPs. For the quadrupole instrument the size detection limits were 20 nm (Au and Ag), 50 (TiO2) and 200 nm (SiO2). For the sector-field instrument size detection limits are lower, 10 nm (Au). Concentration detection limits ranged from 1 ng L−1 for 60 nm Au NPs to 0.1 μg L−1 for 500 nm SiO2 particles. The dynamic range of spICP-MS is limited to two orders of magnitude and as a consequence sample dilution is often required. The precision of the method was found to be <5% and <10% for the determination of particle size and concentration, respectively while the accuracy for particle size (Au NP only) was <10%. The robustness against potential sample matrix components was investigated. The applicability to routine samples was demonstrated by four examples (food, waste water, culture media and biological tissues). The presented combination of spICP-MS measurements with a powerful data evaluation tool enables the use of this technique as a fast, cost efficient and easy to use screening tool for metal and metal oxide NPs that can be widely implemented in the statutory monitoring of food and consumer products for the presence of NPs, as well as in the analytical evaluation of toxicological studies.