NANOTECHNOLOGY-FOOD SAFETY ISSUES

Reproduced below is a contribution from Dr Ramesh V Bhat, an internationally eminent food safety expert which dwells upon the safety issues that confront the food industry because of the application of emerging nanotechnology processes and products. He is Hyderabad based and can be contacted through this blog.

V H Potty
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Maintaining a safe and nutritious food supply is an essential pre-requisite to achieve food security, nutrition and safeguard the general health of the population. Though food is the most regulated commodity in the world, rapid advances in food technology in the globalized era are posing newer challenges to food safety.

Nanosciences and nanotechnologies are new approaches to research and development that concern the study of phenomena and manipulation of materials at atomic, molecular and macromolecular scales, where properties differ significantly from those at a larger scale. Applications for the use of nanotechnology in food products, dietary supplements and their packaging offer tremendous potential. The potential health and environmental risks of nanoscale materials need to be assessed before they are introduced into food. At present there is insufficient data publicly available to reach meaningful conclusions on the potential toxicity of food or color additives incorporating nanomaterials. Nanoparticles may be handled differently in the body than their previously approved, macro counterparts. Information on the bioaccumulation and potential toxic effects of inhalation and/or ingestion of free engineered nanoparticles and their long-term implications for public health is needed. Nanoscale materials may also present new challenges in relation to exposure assessment, including measurement of nanoparticles in the body and in complex food matrices.

Nano-sized particles were found to traverse through heart, lung, transported along nerves, pass through blood brain, blood retinal and blood placental barriers etc. opening the area of nano-toxicology. Potential toxicity could include, generation of reactive oxygen species with concurrent inflammatory response, mitochondrial perturbation producing inner membrane damage, Uptake by reticuloendothelial cells in various organs producing asymptomatic enlargement and potential dysfunction, Protein denaturation and degradation, Uptake in neuronal tissue and DNA damage.

In the past, approval systems for food additives have not generally taken into consideration the particle size of the additive. For nanoparticles, this is obviously an important aspect Future food regulations may therefore need to be more specific in relation to such issues. In 2007, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) affirmed that neither the specifications nor the ADIs for food additives that have been evaluated in other forms are intended to apply to nanoparticulate materials. Recently WHO had provided more information on the safety of Nanoparticles in food.

The European Food Safety Authority (EFSA) has issued a draft opinion that there are broad uncertainties over the safe use of nanotechnology for foodstuffs, and more research is recommended. According to it only a limited number of oral toxicity studies using Engineered Nano Materials (ENM) have been published. Potential intracellular targets of ENM toxicity are e.g. plasma membranes, mitochondria and nucleus. The general mechanisms of injury have been shown to include e.g. lipid peroxidation, ion channel blockage, pore formation, physical disruption, oxidative stress; protein aggregation and DNA damage There are preliminary indications of association of GI disorders with absorption of ENM. There are reports of increased uptake of ENM during GI inflammation, findings of particles in colon tissue in subjects suffering from ulcerative colitis and speculations that ENM exposure might be associated with Crohn’s disease.

Several studies report oral toxicity of 20-60 nm selenium nanoparticles (Se-NP) in rats. With single gavage dosing, sodium-selenite ions were more toxic than the Se-NP . This was confirmed when the Se-NP were administered in feed to rats (2-5 mg/kg; appearance in the feed not defined) for 13 weeks. Single gavage administration to mice of copper nanoparticles (Cu-NP) with average size 23.5 nm was compared to microparticle (MP)-Cu (17 μm) and Cu ions .The doses were high (up to 1,080 mg/kg bw), which caused agglomeration of particles, with intestinal obstruction.. Dose-dependent pathology occurred in kidney, liver, spleen and blood (but not lung, heart, brain, testes or ovaries) in animals exposed to nanoparticles (but not in those exposed to microparticles). After single gavage administration of high doses (5 g/kg bw) of zinc as nanoparticles (58 nm) and MP (1.08 μm) to mice there was GI inflammation in both groups, in spite of attempts to avoid particle agglomeration The toxicity patterns were not consistent: in some aspects, the nanoparticles were more toxic (anemia, kidneys, heart) than the MP, which seemed to be more hepatotoxic. In a later single-dose oral toxicity study of ZnO (1-5 g/kg bw) in mice, two sizes of ENM (20 and 120 nm) were compared to conventional macroscale material. The sizes of the ENM were checked in the gavage, and were found to average 44.8 and 187.5 nm, respectively. Again, the toxicity pattern was complex: the 120 nm ENM were most toxic in stomach, liver, heart, spleen, kidneys and blood, while the 20 nm ENM were similar to the toxicity of the macroscale material (except in pancreas, where they were the most toxic). However, no dose-dependency was observed.

Titanium dioxide (TiO2) nanoparticles (25, 80 and 155 nm) administered as single high-dose 682 gavage (5 g/kg bw) to mice resulted in frequent oesophagus rupture. Titanium dioxide (TiO2) nanoparticles (25, 80 and 155 nm) administered as single high-dose gavage (5 g/kg bw) to mice resulted in frequent oesophagus rupture. The 80 nm particles accumulated predominantly in the liver, the 25 and 155 nm ones accumulated primarily in spleen. Kidney, liver and heart damage was observed with all sizes, with 80 and 155 nm particles producing the most pronounced effects, while blood effects (e.g. increased serum lactate dehydrogenase and alpha-hydroxybutyrate dehydrogenase levels) were most pronounced for the 25 nm particles.

The presence of ENM in food might affect normal food components or contaminants. Lectins used for coatings of nano encapsulates can be cytotoxic or induce inflammatory responses carbon nanotubes with similar characteristics to asbestos, in terms of fibre length, rigidity and persistence, were shown to induce "asbestos-like" granulomatous inflammation after intraperitoneal administration in a mouse model which indicates that the morphology of the ENM affects toxicity. Numerous in vitro studies have shown that some ENM induce oxidative stress at high concentrations. There are some data to indicate possible genotoxic and inflammatory responses in vitro.

A recent intraperitoneal study indicates that fibrous shape of some ENM might be important in determining toxicity. A common finding in the in vitro assays, independent of the ENM studied, seems to be the generation of reactive oxygen species A major consequence of oxidative stress is damage to nucleic acid bases, membrane lipids and proteins. Immune and inflammatory effects can be triggered by oxidative stress and/or production of pro-inflammatory cytokines in the lungs, liver, heart and brain Effects of inhaled ENM on the cardiovascular system include heart rate changes, pro-thrombosis and acute myocardial infarction.

It is prudent to conclude, after taking into account the above observations of the EFSA that more food safety studies and risk analysis carried out before accepting use of nanotechnology for food and beverage.

Dr Ramesh V Bhat