The role of the food matrix and gastrointestinal tract in the assessment of biological properties of ingested engineered nanomaterials (iENMs): State of the science and knowledge gaps

Highlights

• Many foods contain organic or inorganic engineered nanomaterials (ENMs), added either intentionally or unintentionally.

• There is presently a poor understanding of how ingested ENMs (iENMs) behave or interact in foods or the GI tract.

• Understanding the transformations and behavior of iENMs in food and the GI tract are critical to assessing impacts on health.

• Current understanding of the fate of iENMs in the GI tract and critical knowledge gaps requiring research are reviewed.

• Development of standardized methodologies is required to accurately assess the toxicological properties and risks of iENMs.

Abstract

Many foods contain appreciable levels of engineered nanomaterials (ENMs) (diameter < 100 nm) that may be either intentionally or unintentionally added. These ENMs vary considerably in their compositions, dimensions, morphologies, physicochemical properties, and biological responses. From a toxicological point of view, it is often convenient to classify ingested ENMs (iENMs) as being either inorganic (such as TiO₂, SiO₂, Fe₂O₃, or Ag) or organic (such as lipid, protein, or carbohydrate), since the former tend to be indigestible and the latter are generally digestible. At present there is a relatively poor understanding of how different types of iENMs behave within the human gastrointestinal tract (GIT), and how the food matrix and biopolymers transform their physico-chemical properties and influence their gastrointestinal fate. This lack of knowledge confounds an understanding of their potential harmful effects on human health. The purpose of this article is to review our current understanding of the GIT fate of iENMs, and to highlight gaps where further research is urgently needed in assessing potential risks and toxicological implications of iENMs. In particular, a strong emphasis is given to the development of standardized screening methods that can be used to rapidly and accurately assess the toxicological properties of iENMs.

Introduction

Many foods contain organic or inorganic particles that have dimensions in the nanoscale range, generally defined as having at least one dimension < 100 nm (Fig. 1). It is worth pointing out that the 100 nm size cut off is arbitrarily selected and that other properties in addition to size may contribute to the unique properties of such materials. These nanoparticles may be naturally present in foods, intentionally added to achieve a particular functional attribute, or unintentionally introduced through the environment, ingredients, packaging or processing operations (Bellmann et al., 2015, Szakal et al., 2014a, Yada et al., 2014b). Naturally occurring nanoparticles in food include the casein micelles found in milk, which typically have dimensions in the range from a few tens of nanometers to a few hundred nanometers (Holt et al., 2003, Livney, 2010). Organic engineered nanomaterials (ENMs) are often intentionally added to foods or beverages to encapsulate vitamins, nutraceuticals, flavors, colors, or antimicrobials (Livney, 2015, McClements et al., 2015, Shin et al., 2015, Yao et al., 2015b). Inorganic ENMs are intentionally added to foods for numerous reasons: TiO₂ is added to provide opacity and brightness (Weir et al., 2012); SiO₂ nanoparticles are added to modify food texture and powder flow characteristics (Dekkers et al., 2011, Peters et al., 2012); iron oxides (Fe₂O₃ or Fe₃O₄) are added to provide bioavailable iron for nutritional purposes (Raspopov et al., 2011, Zimmermann and Hilty, 2011) or as colorants; and, Ag nanoparticles are added as antimicrobial agents (Hajipour et al., 2012).

ENMs may also be introduced into food products unintentionally during the food manufacturing process. There may be nanoparticles present in the air or the water used within a food processing facility that find their way into the final product. Certain food ingredients containing micron-sized particles have been approved for use in food by regulatory authorities, and are generally regarded as safe (GRAS), without the need of characterization or definition of particle size. However, these ingredients may also contain ENMs that the food manufacturer is unaware of. For example, food grade TiO₂ particles are used as lightening agents to increase the whiteness of foods, and so they are usually designed to have dimensions similar to the wavelength of light (a few hundred nanometers) so as to maximize their light scattering efficiency. However, there may be a population of nano-scale particles present within commercial ingredients (Warheit et al., 2015). For example, food grade TiO₂ (E171 – European designation) contains nano-scale particles (Athinarayanan et al., 2015), and the presence of nano-sized TiO₂ has been reported in dietary supplements (Lim et al., 2015) and certain food products (Peters et al., 2014). Likewise, nanoscale SiO₂ particles have been reported in food grade SiO₂ ingredients (E551) and at levels of up to 14.4 μg/g in commercial foods and dietary supplements (Athinarayanan et al., 2015, Athinarayanan et al., 2014; Dekkers et al., 2011; Lim et al., 2015). Furthermore, mechanical size reduction operations commonly used in the food industry, such as grinding, homogenization, or spray drying, typically produce a distribution of particle sizes, and some of these particles may also fall in the nanoscale range (McClements, 2011). In addition, packaging materials may contain functional ENMs that migrate into a food or beverage product during storage (Abdul Khalil et al., 2016; Aulin et al., 2012; Costa et al., 2014; Dehnad et al., 2014; El-Wakil et al., 2015; Pezzuto et al., 2015). It is also possible that solutes could migrate into a food and precipitate due to the change in their thermodynamic environment, thereby leading to the formation of nanoparticles in a food.

The physicochemical and physiological properties of particles may change considerably when their dimensions fall within the nanoscale range, e.g., chemical reactivity, mechanical strength, digestibility, transport properties, and cellular uptake, accumulation, and distribution (Acosta, 2009; Buzea et al., 2007; Cohen et al., 2014a; Davidson et al., 2016; Konduru et al., 2014, Konduru et al., 2015, Konduru et al., 2016; Lu et al., 2016a, Lu et al., 2016b; Ma et al., 2015; Pirela et al., 2016a, Pirela et al., 2016b; Sisler et al., 2015; Sotiriou et al., 2014; Watson et al., 2014; Yokel et al., 2014; Zhou et al., 2014). These changes are associated with the smaller particle dimensions and higher surface areas of nanoparticles compared to larger particles, as well as to quantum effects taking place in the nanoscale (Pyrgiotakis et al., 2013, Pyrgiotakis et al., 2014).

Consequently, food consumers, manufacturers, and regulators are concerned about the potential health risks associated with ENMs in foods (Bouwmeester et al., 2009; Bugusu et al., 2009; Yada et al., 2014b). Knowledge of the impact of ingested ENM characteristics on their GI fate is currently rather limited. In addition, there is a lack of standardized protocols and methodologies to assess the GI fate of ingested engineered nanomaterials (iENMs), and their potential toxicity (Contado, 2015; Szakal et al., 2014a, Szakal et al., 2014b).

The purpose of this article is to provide a brief overview of the current understanding of the GI fate of iENMs, to outline major knowledge gaps and challenges in assessing their potential toxicological effects, to highlight areas where there is a lack of knowledge, and to indicate where further research is needed.