State of the art on the initiatives and activities relevant to risk assessment andrisk management of nanotechnologies in the food and agriculture sectorsMasami T. Takeuchi, Mina Kojima, Manfred LuetzowPII:DOI:Reference:

S0963-9969(14)00191-4doi: 10.1016/j.foodres.2014.03.022FRIN 5138

To appear in:

Food Research International

Received date:Revised date:Accepted date:

5 August 20137 March 201416 March 2014

Please cite this article as: Takeuchi, M.T., Kojima, M. & Luetzow, M., State of theart on the initiatives and activities relevant to risk assessment and risk management ofnanotechnologies in the food and agriculture sectors, Food Research International (2014),doi: 10.1016/j.foodres.2014.03.022

This is a PDF le of an unedited manuscript that has been accepted for publication.As a service to our customers we are providing this early version of the manuscript.The manuscript will undergo copyediting, typesetting, and review of the resulting proofbefore it is published in its nal form. Please note that during the production processerrors may be discovered which could aect the content, and all legal disclaimers thatapply to the journal pertain.

ACCEPTED MANUSCRIPTTitle: State of the art on the initiatives and activities relevant to risk assessment and risk

T

management of nanotechnologies in the food and agriculture sectors.

RIP

Authors: Masami T. Takeuchia (Corresponding author), Mina Kojimab and Manfred

a

SC

Luetzowc

Food and Agriculture Organization of the United Nations (FAO), Viale delle Terme di

NU

Caracallar, 0153 Rome, Italy, Masami.Takeuchi@fao.org. +39 06 570 53076. bWorld Health

MA

Organization (WHO), 20, Avenue Appia, 1211 Geneva 27, Switzerland. cSaqual GmbH, 5432Neuenhof, Switzerland

ED

Abstract

PT

Food and Agriculture Organization of the United Nations (FAO) and World HealthOrganization (WHO) conducted an international expert meeting on the potential food safety

2009.

ACCE

implications of the application of nanotechnologies in the food and agriculture sectors in June

The present report reviews national, regional and international activities on the riskassessment and risk management of nanomaterials in the food and agriculture sectors thathave been carried out between 2009 and 2012. Information and data have been collected onnational and international approaches that identify and implement strategies to addresspotential hazards associated with the use of nanotechnology-related products or techniques.Selected activities by international governmental and nongovernmental organizations werereviewed and the significant achievements are noted. Meta-analysis of scientific reviewsaddressing risk assessment of nanotechnologies in the food and agriculture sectors wasconducted and key principles for the safety assessment of nanomaterials were identified.

ACCEPTED MANUSCRIPTIt was concluded that although the concepts of potential use of nanomaterials in foodand the implied benefits for stakeholders including consumers have not changed significantly

T

since 2009, there are new products being developed and claimed to enter the market and

RIP

national and international interests in considering the needs for applying regulations onengineered nanomaterials are increasing. The number of published risk assessment of

SC

products used in foods that are nanomaterials or contain particles that fall within applicabledefinitions is growing slowly.

NU

Several data gaps with respect to interaction between nanomaterials and food matrices,

MA

behaviours of nanomaterials in human body, methods to determine such interactions andbehaviours, and the relevance of such data for risk assessment continue to exist. Theinternational collaboration in the area of nanomaterials and nanotechnology in food and

ED

agriculture must be strengthened. International efforts on risk assessment and risk

PT

communication may benefit from the experience gained at national and regional level. Shoulda sufficient number of case studies of risk assessment of commercial products become

ACCE

available with time, a review of approaches applied and results obtained could supportdevelopment of risk assessment procedures acceptable at the international level.

Keywords

Nanotechnology; food safety; agriculture; engineered nanomaterials; manufacturednanoparticles; FAO; WHO

2

ACCEPTED MANUSCRIPT1. IntroductionThe food industry is, like any other sector, driven by innovations, competitiveness and

T

profitability. Therefore the industry is seeking new technologies to offer products with

RIP

improved tastes, flavours, textures, longer shelf-life, and better safety and traceability. Theadvent of nanotechnology has unleashed prospects for the development of new products and

SC

applications for a wide range of industrial and consumer sectors (Roco and Bainbridge, 2001).Many countries have identified the potential of nanotechnology in the food and agriculture

NU

sectors and are investing significantly in its applications to food production, although the

MA

current applications in the food and agricultural sectors are relatively few, because the scienceis still newly emergent. Many countries recognize the need for early consideration of the foodsafety implications of the technology as there is a limited data and information on possible

ED

positive and negative effects that the applications may pose to human health. (FAO/WHO,

PT

2010).

An international expert meeting on the potential food safety implications of the

ACCE

application of nanotechnologies in the food and agriculture sectors was convened by the Foodand Agriculture Organization of the United Nations (FAO) and the World HealthOrganization (WHO) in June 2009. In this work, we have summarized and analyzedinformation that has become available since the 2009 expert meeting in order to determinepossible options for actions to be followed by relevant international organizations like FAOand WHO.2. Material and methodsInformation on relevant risk assessment and risk management activities was gathered fromthe websites of national and international institutions, organizations and governments.Countries were selected to represent a spectrum that is representative from regional point ofview. A systematic review was conducted with the keywords such as nanomaterial, food,

3

ACCEPTED MANUSCRIPTregulation and safety. It should be noted that terms used in this paper reflect thedefinitions applied within the various sources of information; no attempt was made to align

T

the terminology with definitions agreed to by the 2009 expert meeting or other definitions

RIP

applied internationally, for example, by the Codex Alimentarius Commission(http://www.codexalimentarius.org/).

SC

Information on actual and planned uses of nanomaterials resulting in human exposurethrough food or food packaging/contact materials since 2009 was collected from a variety of

NU

sources, including the scientific literature, websites, patent databases, market analysis reports

MA

and material presented at conferences, workshops and symposia.3. Results and Discussion

3.1.Application of nanomaterials in food: current status

ED

Current and projected nanotechnology applications in the food and agriculture were

PT

identified by the FAO/WHO expert meeting report (FAO/WHO, 2010) such as nanostructuredingredients, nanodelivery systems for nutrients, nanosized inorganic and organic food

ACCE

additives, food packaging, nanocoating of food surfaces, nano filtration and no new conceptshave been developed since then. For the years of 2009-2011, 183 patents were identified thatcontain the keywords nano* AND food* in the patent title at http://wokinfo.com. Amongthese patents, 47 related to packaging or coating applications, 19 patents concerned nanoadditives, and 10 patents covered nanotechnology applications for the detection of compoundsin food. The use of nanotechnology and nanomaterials in food and agriculture was also thefocus of a number of review monographs that summarize the status quo or state of art(Chaudry et al., 2010; Frewer et al,. 2011; Huang, 2012).In general, more research on the application of nanomaterials in food is expected. Inparticular, research on nanoemulsion will increase because of the transfer from parallel effortsin the drug delivery sector (ObservatoryNano, 2010). However, there are some barriers to

4

ACCEPTED MANUSCRIPTcommercialization for nanoemulsions. First, suitable food-grade ingredients must beidentified for formulating food nanoemulsions. Second, many of the approaches that have

T

been developed within research laboratories may not be suitable for scale-up to industrial

RIP

production; suitable processing operations must be identified for economic production offood-grade nanoemulsions on an industrial scale. Third, as nanodroplets may have an

SC

enhanced bioavailability, in vivo evaluation of nanoemulsion droplets is required; however,such studies are limited (McClements & Jiajia, 2011).

NU

One specific area of interest is the use of nanomaterials in wastewater treatment to

MA

improve the safety and quality of water used for agriculture, aquaculture and humanconsumption. It might be possible to develop, for example, low-costnanofilter/nanomembrane materials that could be of interest to developing countries.

ED

Technological solutions using nanotechnology in packaging to reduce food losses or facilitate

PT

traceability could be also of interest (FAO/WHO, 2012). The future use of nanomaterials,especially for industrial purposes, has recently raised specific concerns regarding their

ACCE

disposal at the end of their life cycle. Such materials may not be degradable and may persistin the environment where they may interact with compounds in the environment. Thispotential hazard is already causing concern in developing countries to which waste containingnanomaterials may be exported (FAO/WHO, 2012).3.2.Relevant activities at the national/regional level since 20093.2.1. Australia/New ZealandFood Standards Australia New Zealand (FSANZ) recently published an articledescribing its regulatory approach to nanoscale materials in the International Food RiskAnalysis Journal (Fletcher & Bartholomaeus, 2011). The primary focus is not on the size ofthe material per se, but on materials likely to exhibit physicochemical and/or biologicalnovelty. FSANZ differentiates between nanoscale materials that undergo dissolution in water

5

ACCEPTED MANUSCRIPTor oil in the final food or in the gastrointestinal tract and nanoscale or microscale materialsthat are insoluble in water and oil and non-biodegradable, particularly those that may not be

T

readily excreted. FSANZ has not yet received any applications to approve any novel type of

RIP

engineered nanoscale particles for food use, therefore no risk assessments have beenundertaken.

SC

3.2.2. Brazil

Experts from the Brazilian Competitiveness Forum on Nanotechnology met in 2011 to

NU

address the issue of regulating nanotechnology for the industrial sector (NIA, 2011). The

MA

topics discussed during the meeting include the development of possible standards, laws andguidelines for nanotechnology regulation in Brazil (ABDI, 2010).3.2.3. Canada

ED

Regulations in Canada make no explicit reference to nanomaterials at this time. Health

PT

Canada considers any manufactured substance or product and any component material,ingredient, device or structure to be a nanomaterial if it is at or within the nanoscale in at least

ACCE

one external dimension or has internal or surface structure at the nanoscale; or it is smaller orlarger than the nanoscale in all dimensions and exhibits one or more nanoscaleproperties/phenomena (Health Canada, 2011). In order to identify and assess potential risksand benefits of nanotechnology-based health and food products, Health Canada encouragesmanufactures to request a pre-submission meeting with the responsible regulatory authority todiscuss the type of information that may be required for their products safety assessment.3.2.4. ChinaThe Food Safety Law, which came into effect in 2009, does not contain any legislationrelating to nanomaterials (Food Safety Law of China, 2009). Until now, applications for usingnanominerals or food ingredients have not been accepted by regulatory authorities, but thesafety evaluation of nanotechnology in foods continues to be discussed.

6

ACCEPTED MANUSCRIPT3.2.5. European Union (EU)Based on the opinion that was published by the Scientific Committee on Emerging

T

and Newly Identified Health Risks Scientific basis for the definition of the term nanomaterial

RIP

(SCENIHR, 2010), the European Commission (EC) adopted the following recommendationon the definition of nanomaterials: Nanomaterial means a natural, incidental or

SC

manufactured material containing particles, in an unbound state or as an aggregate or as anagglomerate and where, for 50% or more of the particles in the number size distribution, one

NU

or more external dimensions is in the size range 1 nm 100 nm (EC, 2011). A common

MA

system for authorisation of food additives in Europe requires re-evaluation of the safety ofany food additive to ensure that, once permitted, food additives are kept under continuousobservation and re-evaluation. This assures that an approved additive produced by a different

ED

production process (e.g. to generate nano-form) will undergo re-evaluation of safety.

PT

The European Food Safety Authority (EFSA) published a scientific opinion with thetitle Guidance on the risk assessment of the application of nanoscience and nanotechnologies

ACCE

in the food and feed chain (EFSA Scientific Committee, 2011). EFSA concluded that the riskassessment paradigm including hazard identification and hazard characterisation followed byexposure assessment and risk characterisation is appropriate for these applications ofnanoscience and nanotechnologies in the food and feed chain (EFSA, 2009). The EFSA hasset up a scientific network on the risk assessment of nanotechnology in food and feed, inwhich all member states are represented, to create an overview of national research activitiesto facilitate collaboration and exchange of information[http://www.efsa.europa.eu/en/supporting/pub/362e.htm].3.2.6. JapanNanotechnology was specified as one of the priority research targets in the thirdScience and Technology Basic Plan for 2006-2010 by the Japanese government (Government

7

ACCEPTED MANUSCRIPTof Japan Council for Science and Technology Policy, 2006). A survey results on the use ofnanotechnology in the food sector funded by the Food Safety Commission Japan (FSCJ)

T

reported that there was no need for specific nanomaterial regulation at present in Japan (FSCJ,

RIP

2010). However the report concluded that there were questions on the classification ofnanotechnology-using food products as well as significant data gaps, which precluded the

SC

drawing from firm conclusions. If any regulation needed to be introduced, safety assessmentmethods would need to be established first.

NU

3.2.7. Malaysia

MA

Nanotechnology has been identified by the National Innovation Council as anessential element to meet the countrys objective to turn Malaysia into a high incomedeveloped nation by 2020. Under the National Nanotechnology Directorate, legal instruments,

ED

appropriate parameters and monitoring mechanisms ensure compliance with all aspects of

PT

nanotechnology development and commercialization. Malaysia is formulating a clearroadmap to comply with any future global safety standards relevant to nanotechnology.

ACCE

At present there are no specific regulations applicable to the risk assessment ofnanotechnology in Malaysia. Risk assessment is conducted to address potential health risks ingeneral and is not limited to nanotechnology.3.2.8. Republic of Korea

No regulations relating to nanomaterials were found on government websites , the 3rdInternational Nanomaterials Ethics Workshop in 2011, topics including changes in safetyregulation regarding nanomaterials in European countries were discussed (Korean Ministry ofEducation, Science and Technology, 2011). The Korean Ministry of the Environmentdeveloped a document on the Guideline for the life cycle assessment (LCA) for nanomaterials,as reported in Organisation for Economic Co-operation and Development (OECD) (OECD,2011).

8

ACCEPTED MANUSCRIPT3.2.9. Russian FederationThe control of nanomaterials in various industry sectors, including food and

T

agricultural production receive attention by the Federal Service for Surveillance of Consumer

RIP

Rights Protection and Human Well-Being (Rospotrebnadzor) since 2007. Several federalministries and scientific bodies developed the concept of toxicological researches,

SC

methodology of risk assessment, methods of identification and quantitative determination ofnanomaterials (No. 79, 31.10. 2007) which notes that the set of the stated factors testifies to

NU

nanomaterials processing physical and chemical properties and biological (including toxic)

MA

action, differing from substances in a usual physical and chemical condition. In thisconnection they have to be referred in all cases to new types of materials and production,which characteristic of potential risk for human health and environment is compulsory in all

ED

cases.

PT

Under the umbrella of a federal programme bythe development of infrastructure ofNanoindustry in the Russian Federation for 2008-2010, in total 50 standard and methods

ACCE

document (guidelines and recommendations) for safety assessment and risk evaluation of thenanotechnologies and nanomaterials were developed and approved. A predictive assessmentallows to classify nanomaterials as having high, average or low level of potential hazard. Therisk evaluation of nanoparticles and nanomateirals in the food sector is based on thetraditional scheme which was developed and approved for the assessment of chemical andother technological hazards. The risk assessment processes are carried out in accordance withguidelines and recommendations generally harmonized with requirements of OECD, EFSA,FAO/WHO and other international and national bodies.As of 2012 safety assessment of a number of nanomaterials used in production of foodand agricultural designation were carried out by the Institute of Nutrition of the RussianAcademy of Medical Science. Until now such work allowed to characterise nanoparticles of

9

ACCEPTED MANUSCRIPTtitanium dioxides, silicon, aluminium and iron, the nanostructured clays (nanoexfoliated clay),fullerene C60, metal silver (Tutelyan, 2013)

T

3.2.10. South Africa

RIP

No safety assessment or regulations specific to nanomaterials in the food andagriculture sectors were found on the Government of the Republic of South Africas website

SC

(Government of the Republic of South Africa, 2008). South Africas national nanotechnologystrategy runs until 2014 to support long-term nanoscience research (Department of Science

NU

and Technology of the Republic of South Africa, 2011)3.2.11. Switzerland

MA

The Swiss Federal Council launched the Action Plan for Synthetic Nanomaterialsthat illustrate the work required for the safe handling of nanomaterials which serves as a

ED

framework until 2015. The plan addresses development of regulatory framework conditions

PT

for the responsible handling of synthetic nanomaterials, creation of scientific and methodicaltools aimed at identifying and preventing potential harmful effects of synthetic nanomaterials

ACCE

on health and the environment, and the promotion of the public dialogue on opportunities andrisks of nanotechnology. Safety provisions for use of nanomaterials in foods is covered byexisting regulations and procedures. Pesticides are subject to an approval procedure whichspecifically asks for nanospecific information. So far the Federal Office of Public Health hasnot received any requests for approval of food additives containing nanomaterials. Possiblefuture requests would be handled analogously to those for a new, as-yet unlisted additives.The same would apply to requests for packaging materials containing nanomaterials whichcome into contact with foodstuffs.3.2.12. United States of AmericaIn addressing issues raised by nanomaterials, United States (US) agencies adhere tothe principles for regulation and oversight of emerging technologies, as summarized by

10

ACCEPTED MANUSCRIPTHoldren, Sunstain & Siddiqui (2011). The United States Food and Drug Administration(FDA) is in the process to finalize a guidance document on considering whether an FDA

T

regulated product contains nanomaterials or otherwise involves the use of nanotechnology.

RIP

The draft guidance on substances to be used in dietary supplements proposes to include issuesrelated to nanotechnology, if such use of nanotechnology results in new or altered properties

SC

of the ingredient (FDA, 2011). Another guidance document is also being developed, whichaddresses the impact that manufacturing changes, including a change in particle size, would

NU

have on the regulatory status of authorized materials, which will address nanomaterials (FDA,

MA

2012). The FDA does not maintain a list of nanomaterials that it has assessed (A. McCarthy,FDA, personal communication, 2011).

The nanomaterial research strategy from 2009 defines the US Environmental Protection

ED

Agency (EPA)s nanotechnology research programme to conduct focused research on

PT

nanomaterial safety (EPA, 2009). The EPA has identified five nanomaterial types forinvestigation that are widely used in products or have been recognized for their potential uses

ACCE

(EPA, 2011). The materials being studied include carbon tubes and fullerenes, cerium oxide,titanium dioxide and silver.

3.3.Relevant activities by international governmental and nongovernmentalorganizations since 2009In the last few years, the Institute of Food Technologists (IFT) has supported research andpublished several articles on nanotechnology relating to an ongoing project on safetyassessment. IFT offers an on-demand online courses including Introduction to Nanoscience.There have been many scientific literature published on the IFT journals and IFT conferenceshave featured many sessions on the topic of nanotechnology.The NanoRelease project from the International Life Sciences Institute (ILSI) ResearchFoundations Center for Risk Science Innovation and Application aims to promote the safe

11

ACCEPTED MANUSCRIPTdevelopment of nanomaterials by supporting the development of methods to understand therelease of nanomaterials used in products. As part of the NanoRelease project, data, methods,

T

guidance, standards and links are collected(ILSI, 2011). NanoCharacter is another project

RIP

aimed at developing a framework and road map for implementing widespread adoption ofprinciples of reporting characteristics of nanomaterials in studies of commercial nanoproducts.

SC

The project builds on other international efforts to establish the list of what to measure andwill lay out how to get from concept to reality of consistent reporting. ILSI Europe initiated

NU

the Novel Foods and Nanotechnology Task Force (ILSI Europe, 2011), which started its work

MA

focusing on new technologies for the safety/nutritional assessment of novel foods and foodingredients. ILSI Europe has developed a peer-reviewed article on the safety assessment ofengineered nanomaterials in food (Cockburn et al., 2012).

ED

International Organization for Standardization (ISO) established the Technical

PT

Committee 229 Nanotechnologies with the scope of standardization in the field ofnanotechnologies. Specific tasks include developing standards for: terminology and

ACCE

nomenclature; metrology and instrumentation, including specification for reference materials;test methodologies; modelling and simulations; and science-based health, safety, andenvironmental practices (http://isotc.iso.org/livelink/livelink/open/tc229).Organisation for Economic Co-operation and Development (OECD) has two relevantworking parties: (1) the Working Party on Nanotechnology and (2) the Working Party onManufactured Nanomaterials. Both working parties do not have food as a main subject;nevertheless, OECDs work on the testing and assessment of nanomaterials can be used forfood-related nanomaterial applications (M. Gonzalez, OECD, personal communication, 2011).OECDs main activities are on: hosting database on research into the safety of manufacturednanomaterials; safety testing of representative set of manufactured nanomaterials; defining therole of alternative test methods in nanotoxicology; developing manufactured nanomaterials

12

ACCEPTED MANUSCRIPTand test guidelines; developing voluntary schemes and regulatory programmes; conductingprojects to evaluate environmental risk assessment approaches; and conducting projects to

T

investigate the potential benefits of applications based on the use of manufactured

RIP

nanomaterials for environmentally sustainable use of nanotechnology.

Overall there have been a number of meetings, symposia and workshops on the topic of

SC

nanomaterials organized by several international or regional bodies at global, regional andnational levels. In many unique ways, these events discussed the current status of the

NU

technology and future possible needs, however there has not been a conclusive remarks on

MA

how the risk assessment and risk management of nanomaterials in food and agriculture sectorsshould be conducted. This confirms that this is the area that requires further active dialoguesamong various stakeholders in many parts of the world.

ED

3.4.Scientific reviews addressing risk assessment of nanotechnologies in the food and

PT

agriculture sectors

Recent scientific reviews on risk assessment of nanotechnologies in the food and agriculture

ACCE

sectors confirm that information on this topic is limited (Tran & Chaudhry, 2010; Card et al.,2011; Horie & Fujita, 2011; Magnuson, Jonaitis & Card, 2011; Morris, 2011; Rico et al.,2011; Krug & Wick, 2011). A review on the interaction of nanoparticles with edible plantsfound that understanding of plant toxicity is at the early stages. Few studies have beenperformed on the accumulation of engineered nanomaterials in crop plants such as rape,radish, lettuce, corn and cucumber (Rico et al., 2011). Rico et al. (2011) noted that among thestudied nanomaterials, the carbon-based nanomaterials fullerenes C70 and fullerols C60(OH)20and most of the metal-based nanomaterials (titanium dioxide, cerium oxide, magnetite, zincoxide, gold, silver, copper and iron) accumulated in the plants. These compounds stored in theplants can be transferred to consumers. Depending on the studied nanomaterial and plant,

13

ACCEPTED MANUSCRIPTnegative effects of the nanoparticles on the food crops were observed, such as reducedgermination, reduced root growth and delayed flowering.

T

Card et al. (2011) evaluated published literature on the safety of oral exposure to food-

RIP

related nanomaterials and found that there are currently insufficient reliable data to allow aclear safety assessment. Card et al. (2011) also considered that non-food-related engineered

SC

nanomaterials require evaluation of oral toxicity in light of possible contamination of the foodsupply. Morris (2011) concluded that the lack of information on the possible toxicity of

NU

nanomaterials makes it difficult to assess the safe or Acceptable Daily Intake. According to

MA

Magnuson, Jonaitis & Card (2011), the literature on the safety of oral exposure tonanomaterials inadequately characterizes nanomaterials with insufficient physicochemicalparameters, concluding that Unless nanomaterials are adequately characterized, the results of

ED

the toxicology studies cannot be utilized to predict toxicity of other nanomaterials as changes

PT

in any of the characteristics may result in changes in biological activity.The safety assessment of nanomaterials will depend on their adequately characterized

ACCE

chemical properties; critical parameters include biopersistence and digestibility. Based on thedevelopment of nano forms of trace minerals, the group led by D. Pereira (2012) at MedicalResearch Council, UK Human Nutrition Research identified three different scenarios.

Digestible, non-biopersistent nanomaterials such as nano forms of a salt will be digested(dissolve) prior to any cellular exposure; for cells and tissues, there will be no difference ifcompared with conventional forms. A second type of digestible, non-biopersistentnanomaterial, such as micellar nano formulations or ferritin, will only partially degrade in thegut; they may therefore be absorbed as nano structures but will be rapidly broken down incells (Powel et al 2013). A third type, non-digestible, biopersistent nanomaterials, may remainintact and will raise different issues, an important one being their adsorbed surface materials,

14

ACCEPTED MANUSCRIPTwhich may be removed in the stomach and replaced in the gut by luminal molecules before

T

cellular uptake (FAO/WHO, 2012).

RIP

4. Conclusions

The concepts of potential use of nanomaterials in food and the implied benefits for

SC

stakeholders including consumers have not changed significantly since 2009. New productsare being developed and claimed to enter the market, but the available data from published

NU

sources and databases do not allow verifying whether product ideas are just concepts,

MA

unsubstantiated claims, or are already resulting in exposure of consumers to food beingproduced with nanotechnology/nanomaterials at any significant rate.The statement by the FAO/WHO expert meeting (FAO/WHO, 2010) that current risk

ED

assessment approaches were suitable to assess nanomaterials and nanotechnologies used in

PT

food is supported by those agencies/institutions that have investigated this issue in more detail.National and regional food safety agencies increased their focus during the past few years on

ACCE

investigating the implications of nanomaterials added to or used with food. Policies andguidance documents have been published that allow a better understanding of how riskassessment of nanomaterials will be performed in the future. OECD reviewed their testingguidelines for hazard identification and characterization of food chemicals and found them tobe generally applicable for the testing of nanomaterials. Other research-oriented projectsinitiated by OECD will provide valuable insights into aspects of risk assessment specific toengineered nanomaterials. The approach to be published by ILSI for nanomaterials to be usedin food is interesting, as it tries to systematically review the information already available forconventional material and discusses what properties would allow extrapolation fromconventional to novel nanomaterials. Further development and implementation of this conceptmay lead to reduced animal testing. The main areas of chemical risk assessment at the

15

ACCEPTED MANUSCRIPTinternational level address food additives, pesticide residues, veterinary drug residues, someprocessing aids, such as enzymes, and occasionally micro-nutrients. Nanomaterials would be

T

within the scope of such activities; for example, a nanoscale food additive could be addressed

RIP

by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), and residues from ananoscale pesticide could be addressed by the Joint FAO/WHO Meeting on Pesticide

SC

Residues (JMPR). There are, however, some areas of food chemicals, such as materials incontact with foods (e.g. food packaging), that occasionally are addressed by FAO/WHO

NU

expert bodies, but for which no comprehensive and systematic programme is in place; for a

MA

nano-plastic material to be used in food packaging, there is no risk analysis framework atthe international level currently in place. Several data gaps with respect to interaction betweennanomaterials and food matrices, behaviours of nanomaterials in human body, methods to

ED

determine such interactions and behaviours, and the relevance of such data for risk assessment

PT

continue to exist. Coordinated international collaboration and information exchange between

useful.

ACCE

scientists from academia, industry and authorities, to address such gaps may be necessary and

A key finding of the FAO/WHO expert meeting was that public confidence in engineerednanomaterials can be supported through institutional efforts to provide an overview ofapplications of nanotechnology in food and packaging that are transparent and allow publicinvolvement (FAO/WHO, 2010). It was found that the mandatory labelling would lead togreater transparency for the consumer and enable consumer freedom of choice. However,mandatory labelling could also lead to the avoidance of the use of nanotechnologies inconsumer products, including those that are beneficial (Grure, 2011). So far, apart from theEU, no country has set a regulatory framework for the mandatory labelling of nanomaterialsin food (EU, 2011). The mandatory labelling of materials that meet a definition that reflectsonly dimension (i.e. is not risk based) provides a new element in the discussion that might be

16

ACCEPTED MANUSCRIPTof interest to the Codex Alimentarius Commission, as it could result in technical barriers totrade of foods to which nanomaterials have been added. In a report on the ECs public online

T

consultation among key stakeholders about nanomaterials, the majority of the 716

RIP

respondents regarded applications in agriculture and food with more scepticism than

SC

applications in other areas (EC, 2010).

Acknowledgements

NU

This work was conducted jointly by FAO and WHO, however the opinions or assertions

MA

contained herein are our private views and are not to be construed as official or as reflectingthe view of FAO or WHO. M. Luetzow designed and conducted the research and analyzedand organized the information/data collected. M. Takeuchi facilitated the development

ED

process of the research and analysis, and prepared the article. M. Kojima contributed in

PT

reviewing the information and the article. We acknowledge the responses and commentsprovided by various international experts. Technical contributions from several FAO and

ACCE

WHO colleagues are also gratefully appreciated.

References

ABDI (Brazilian Agency for Industrial Development). (2010). Estudo ProspectivoNanotecnologia. Braslia, Brazilian Agency for Industrial Development, Available atAccessed 23 November 2011.Card, J. W., Jonaitis, T. S., Tafazoli, S. & Magnuson, B. A. (2011). An appraisal of thepublished literature on the safety and toxicity of food-related nanomaterials. Critical Reviewsin Toxicology, 41(1), 2049.

17

ACCEPTED MANUSCRIPTChaudhry, Q., Castle, L. & Watkins, R. (eds.) (2010). Nanotechnologies in Food. London:Royal Society of Chemistry Publishers.

T

Cockburn, A., Bradford, R., Buck, N., Constable, A., Edwards, G., Haber, B., Hepburn, P.,

RIP

Howlett, J., Kampers, F., Klein, C., Radomski. M., Stamm, H., Wijnhoven, S. & Wildemann.T. (2012). Approaches to the safety assessment of engineered nanomaterials (ENM) in food.

SC

Food and Chemical Toxicology, 50(6), 22242242.

Department of Science and Technology of the Republic of South Africa. (2011). The national

NU

nanotechnology strategy. Pretoria, Department of Science and Technology, Available atAccessed 23 November 2011.

MA

EC. (2010). Report on the European Commissions public online consultation. Towards astrategic nanotechnology action plan (SNAP) 20102015. European Commission, Available

ED

at Accessed 6 December 2011.

PT

EC. (2011). Commission Recommendation of 18 October 2011 on the definition ofnanomaterial. Official Journal of the European Union, L 275, 3840, Available at Accessed25 October 2011.

EFSA. (2009). Scientific opinion of the Scientific Committee on a request from the EuropeanCommission on the potential risks arising from nanoscience and nanotechnologies on foodand feed safety. EFSA Journal, 958, 139, Available atAccessed 25 October 2011.EFSA Scientific Committee. (2011). Scientific Opinion on Guidance on the risk assessmentof the application of nanoscience and nanotechnologies in the food and feed chain. EFSAJournal, 9(5), 2140, Available atAccessed 25 October 2011.

18

ACCEPTED MANUSCRIPTEPA. (2009). Nanomaterial research strategy. Washington, DC, United States EnvironmentalProtection Agency, Office of Research and Development (EPA 620/K-09/011), Available at

T

Accessed 7

RIP

November 2011.

EPA. (2011). Types of nanomaterials under investigation by the EPA. Washington, DC,

SC

United States Environmental Protection Agency, Available at

Accessed 7 November

NU

2011.

MA

EU. (2011). Regulation (EU) No 1169/2011 of the European Parliament and of the Council of25 October 2011 on the provision of food information to consumers, amending Regulations(EC) No 1924/2006 and (EC) No 1925/2006 of the European Parliament and of the Council,

ED

and repealing Commission Directive 87/250/EEC, Council Directive 90/496/EEC,

PT

Commission Directive 1999/10/EC, Directive 2000/13/EC of the European Parliament and ofthe Council, Commission Directives 2002/67/EC and 2008/5/EC and Commission Regulation

ACCE

(EC) No 608/2004. Official Journal of the European Union, L 304. 1863, Available atAccessed6 December 2011.

FAO/WHO. (2010). FAO/WHO expert meeting on the application of nanotechnologies in thefood and agriculture sectors. Potential food safety implications. Meeting report. Rome: FAOand WHO, Available at Accessed 15 July 2013.FAO/WHO. (2012). Joint FAO/WHO Seminar on Nanotechnologies in food and agriculture,27 March 2012. Rome: FAO. Available at

19

ACCEPTED MANUSCRIPT

Accessed 15 July 2013.

T

FDA. (2011). Draft guidance for industry: Dietary supplements: New dietary ingredient

RIP

notifications and related issues. Silver Spring, MD, United States Food and DrugAdministration, Center for Food Safety and Applied Nutrition, Available at

SC

Accessed 16 February 2012.

NU

FDA. (2012). Guidance for Industry. Assessing the Effects of Significant Manufacturing

MA

Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status ofFood Ingredients and Food Contact Substances, Including Food Ingredients that are Color

Administration, Available at

ED

Additives (Draft guidance for industry). Silver Spring, MD, United States Food and Drug

PT

rma>tion/GuidanceDocuments/UCM300927.pdf>Accessed 1 February 2013.

ACCE

Fletcher, N. & Bartholomaeus, A. (2011). Regulation of nanotechnologies in food in Australiaand New Zealand. International Food Risk Analysis Journal, 1(2), 33-40.Food Safety Law of China. (2009). The Food Safety Law of the Peoples Republic of China.Procedural Law Research Institution at China University of Political Science and Law,Available atAccessed 4January 2012.Frewer, L., Norde, N., Fischer, A. & Kampers, F. (eds.) (2011). Nanotechnology in the AgriFood Sector: Implications for the future. Weinheim: Wiley-VCH Verlag.FSCJ. (2010). A basic survey report on safety assessment information on the use ofnanotechnology in the food sector. Conducted by the Toray Research Center as A

20

ACCEPTED MANUSCRIPTcomprehensive study for ensuring food safety under the Cabinet Office Food SafetyCommission (FY 2009) for the Food Safety Commission of Japan, Available at

T

Accessed 16

RIP

January 2012.

Government of Japan Council for Science and Technology Policy. (2006). Science and

SC

technology basic plan [provisional translation]. Tokyo, Government of Japan, Council forScience and Technology Policy, Available at Accessed 8 November 2011.

MA

Government of the Republic of South Africa. (2008). Foodstuffs, Cosmetics and DisinfectantsAmendment Act, 2007. Government Gazette, Vol. 512, No. 30822, 28 February 2008,Available at Accessed 23

ED

November 2011.

PT

Grure, G. P. (2011). Labeling nano-enabled consumer products. Nano Today, 6(2), 117121.Health Canada. (2011). Policy statement on Health Canadas working definition for

ACCE

nanomaterial. Ottawa, Health Canada, Available at Accessed 8 November 2011.Holdren, J. P., Sunstein, C. R. & Siddiqui, I. A. (2011). Principles for regulation andoversight of emerging technologies. Memorandum for the heads of executive departments andagencies from the Office of Science and Technology Policy, the United States TradeRepresentative and the Office of Information and Regulatory Affairs, Available at Accessed 8 November 2011.Horie, M. & Fujita, K. (2011). Chapter 4: Toxicity of metal oxides nanoparticles. In Fishbein,J. C. (ed.), Advances in molecular toxicology, Vol. 5. Amsterdam: Elsevier B.V.

21

ACCEPTED MANUSCRIPTHuang, Q. (Ed.) (2012). Nanotechnology in the Food, Beverage and Nutraceutical Industries.Cambridge, UK: Woodhead Publishing Ltd.

T

ILSI. (2011). Developing methods to measure release of nanomaterials from solid matrices.

RIP

Washington, DC, International Life Sciences Institute Research Foundation, Availalble at Accessed 26 October

SC

2011.

Sciences Institute Europe, Available at

NU

ILSI Europe. (2011). Novel Foods and Nanotechnology Task Force. International Life

MA

Accessed 26 October 2011.Korean Ministry of Education, Science and Technology. (2011). The 3rd International

Technology, Available at

ED

Nanomaterials Ethics Workshop. Seoul, Korean Ministry of Education, Science and

PT

Accessed 23 November 2011.Krug, H. F. & Wick, P. (2011). Nanotoxikologie eine interdisziplinre Herausforderung.Angewandte Chemie, 123, 12941314.Magnuson, B. A., Jonaitis, T. S. & Card, J. W. (2011). A brief review of the occurrence, use,and safety of food-related nanomaterials. Journal of Food Science, 76(6), R126R133.McCarthy, FDA (2011) Personal communication. Interview by M. Luetzow [Telephone].Food and Agriculture Organization of the United Nations, Rome, Italy.McClements, D. J. & Jiajia, R. (2011). Food-grade nano-emulsions; formulation, fabrication,properties, performance, biological fate, and potential toxicity. Critical Reviews in FoodScience and Nutrition, 51(4), 285-330.

22

ACCEPTED MANUSCRIPTMorris, V. J. (2011). Emerging roles of engineered nanomaterials in the food industry. Trendsin Biotechnology, 29(10), 509516.

T

NIA (Nanotechnology Industries Association). (2011). Brazilian Competitiveness Forum on

RIP

Nanotechnology discusses nanotechnology regulation. Brussels: Nanotechnology IndustriesAssociation, Available at Accessed 23 November2011.

NU

ObservatoryNANO. (2010). Observatory Nano factsheets 2009-2010. Project funded by the

MA

European Unions framework programme, Available at

Accessed 15 July 2013.OECD. (2011). National activities on life cycle assessment of nanomaterials. Paris,

ED

Organisation for Economic Co-operation and Development, Available at

PT

Accessed 2 January 2012.

ACCE

Pereira (2012). Personal communication. FAO/WHO Seminar. Food and AgricultureOrganization of the United Nations, Rome, Italy.Powell, J. J., Bruggraber, S. F. A., Faria, N., Poots, L. K., Hondow, N., Pennycook, T. J.,Latunde-Dada, G. O., Simpson, R. J., Brown, A. P. & Pereira, D. I. A. A nano-disperseferritin-core mimetic that efficiently corrects anemia without luminal iron redox activityNanomedicine. 6 January 2014 (in Press).Rico, C. M., Majumdar, S., Duarte-Gardea, M., Peralta-Videa, J. R. & Gardea-Torresdey, J. L.(2011). Interaction of nanoparticles with edible plants and their possible implications in thefood chain. Journal of Agricultural and Food Chemistry, 59(8), 34853498.Roco, M. C. & Bainbridge, W. S. (eds.) (2001). Societal implications of nanoscience andnanotechnology. Boston: Kluwer Academic Publishers, (pp. 3-4).

23

ACCEPTED MANUSCRIPTSCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks, EuropeanCommission). (2010). Scientific basis for the definition of the term nanomaterial. European

T

Commission, Directorate-General for Health & Consumers, Scientific Committee on

RIP

Emerging and Newly Identified Health Risks, Available at

SC

Accessed 28 October 2011.

Tran, L. & Chaudhry, Q. (2010). Chapter 8: Engineered nanoparticles and food: an

NU

assessment of exposure and hazard. In Chaudhry, Q., Castle, L. & Watkins, R. (eds.),

MA

Nanotechnologies in food. Cambridge, UK: The Royal Society of Chemistry, RSC Publishing.Tutelyan, V. A. (2013). The control over nanomaterials. Russian Federation. Letter sent in

ACCE

PT

ED

response to the request for public review.

24