In a review published on December 21, 2016 in the peer-reviewed journal Food Additives & Contaminants: Part A, Maryam Jokar and colleagues from the National Food Institute at the Technical University of Denmark summarize the current literature on the migration of engineered nano-objects (ENOs) from polymer-based food contact materials (FCMs). The authors identify knowledge gaps and formulate “six open questions” concerning ENO migration from FCMs, and potential human health risks:

  1. «Can ENOs migrate from FCMs at all?»

Currently, there is no agreement on ENO migration from FCMs. Some studies observed no migration of nanoparticles (FPF reported), and modeling studies claimed that migration is highly improbable for ENOs larger than 10 nm (which includes the majority of ENOs in FCMs). However, other experimental studies have reported on detecting the migration of ENOs sized 50, 100, and even up to 1000 nm (FPF reported).

  1. «If migration of ENOs occurs, what is the migration mechanism?»

The review authors point out that currently the most frequently assumed mechanism for ENO migration from FCMs is simple diffusion. However, the diffusion concept has been developed for low molecular weight compounds, which are significantly smaller than most nanoparticles. The authors suggest a rough estimation stating that the molecular weight of nanoparticles with a diameter of 1 and 10 nm would be 314 Da and 314 kDa, respectively. Hence, “diffusion may not be the major responsible mechanism for ENO migration,” the authors conclude. They point out that ENO migration can occur by three other mechanisms, including “(1) desorption of the ENO from the FCM surface, (2) dissolution of the ENO, and (3) degradation of the polymer matrix surrounding the ENO,” and provide examples of experimental evidence in support of these mechanisms. Hence, further research is needed to understand the exact mechanisms as well as external factors governing the release of ENOs from polymeric FCMs.

  1. «What are suitable analytical techniques for studying the migration of ENOs from FCMs?”

Analytical methods are expected to deliver information on the identity and quantity of a migrating substance. The challenge regarding ENOs is that their ‘identity’ is defined not only by their chemical composition itself but also by other parameters such as size, shape, porosity, or surface coating. Hence, ENO analytics should not only detect and quantify ENOs in the food or food simulant, but also characterize their relevant physico-chemical properties. At the moment, no single analytical technique exists that can fulfil all these requirements, the authors conclude. They point out that the analysis of ENO migration suffers from “the lack of validated methods and of suitable reference materials to assure accuracy of the results with respect to determined sizes and concentrations.” The existing difficulties in detection and characterization of ENOs pose a serious limitation to the risk assessment of nanomaterials due to the “general lack of (high-quality) exposure data.”

  1. «Are standard food simulants and migration test conditions for plastic FCMs appropriate for studying the migration of ENOs?»

The authors argue that not only the food simulants, but also the testing conditions recommended by the current regulation for plastic FCMs may not be suitable for testing of ENO migration from FCMs. This is because the size, shape, or chemical composition of ENOs may change depending on the food or food simulant – a ‘novel’ feature of ENOs that is still poorly understood. For example, some studies have suggested that acetic acid could facilitate not only dissolution, but also agglomeration or aggregation of silver nanoparticles. Others have observed secondary formation of nanoparticles following metal migration into food in ionic form. Furthermore, because ENOs are likely to be released by a mechanism other than diffusion, it should be generally questioned whether the ‘worst-case’ migration conditions designed for low molecular weight compounds migrating from plastics can be automatically seen as ‘worst-case’ conditions for ENO migration. Before the proper migration testing conditions are defined for ENOs, more data are needed “to understand how the properties of migrated ENOs change as function of time and temperature.” Furthermore, the authors suggest that, while most nanocomposites may still be tested by conventional immersion-based procedure, there are additional factors that must be considered, such as “mechanical forces (abrasion, vibration), microwave treatment, heating and UV exposure.” These factors, occurring during the ‘real-life’ use of FCMs, may have a large influence on the release of ENOs.

  1. «Can mathematical modelling be applied for predicting the migration of ENOs from FCMs?»

So far, all mathematical models for ENO migration from FCMs have assumed diffusion as the main mechanism for migration, and have consequently predicted negligible migration for ENOs larger than a few nanometers in size. However, as reviewed above in question 2, diffusion is likely not the main mechanism governing the release of ENOs from FCMs, and experimental studies have observed the migration of much larger ENOs from FCMs. Hence, diffusion-based models are only applicable to very small nanoparticles, which are mostly irrelevant for FCM nanocomposites. To deliver a reliable prediction of ENO migration from FCMs, new mathematical models that are able to account for additional migration mechanisms, such as dissolution of the ENO, desorption processes, and polymer degradation, should be developed.

  1. «What are the risks of human exposure associated with migrating ENOs?»

The authors review the three principles relevant for nanoparticle toxicology, including the ‘transport principle,’ the ‘surface principle,’ and the ‘material principle.’ A particular challenge with evaluating the toxicity of ENOs is that “their physico-chemical properties can change in different environments.” Currently, little is known about the behavior and fate of ENOs in the human body, in particular on the interactions and transformations in the gastrointestinal tract, crossing of the gut wall, or distribution to other organs. For example, although in vitro digestion models have been recommended to study these interactions, recent research has demonstrated that “in vitro digestion protocols for nanoparticles without food components may lead to misleading and inconclusive results of ENO uptake” (FPF reported). In addition, the authors suggest that ENOs should also be evaluated for their influence on the food matrix, because they are known to interact with various functional groups of organic molecules.

In conclusion, the authors suggest that the six open questions they have identified should guide further research on the safety of nanocomposite FCMs. Although their review focused on polymer-based FCMs, similar considerations are likely to also apply to ENO migration from non-plastic FCMs.

Read more

Jokar, M., et al (2016). “Six open questions about the migration of engineered nano-objects from polymer-based food-contact materials: a review.Food Additives & Contaminants: Part A (published December 21, 2016).