Following a request from the European Commission the Scientific Committee was asked to prepare a guidance document for the safety assessment of applications involving the application of nanoscience and nanotechnology to food and feed. This scientific opinion offers practical guidance for the risk assessment of applications involving the use of Engineered Nanomaterials (referred to as the ENM Guidance) in the food and feed chain (including food additives, enzymes, flavourings, food contact materials, novel foods, feed additives and pesticides).
The risk assessment paradigm (hazard identification and hazard characterisation followed by exposure assessment and risk characterisation) is appropriate for these applications. Consequently relevant data and information for the various steps should be made available to the risk assessor to carry out a risk assessment.
Adequate characterisation of ENM is essential for establishing its identity and physico-chemical forms in food/feed products and under testing conditions. The physico-chemical parameters may change in various environments and the characterisation of ENM should ideally be determined in five stages, i.e. as manufactured (pristine state), as delivered for use in food/feed products, as present in the food/feed matrix, as used in toxicity testing, and as present in biological fluids and tissues.
The risk of an ENM will be determined by its chemical composition, physico-chemical properties, its interactions with tissues, and potential exposure levels. The physico-chemical characterisation is needed to identify an ENM and decide whether the ENM Guidance is appropriate. If the ENM Guidance is applicable, the results from the testing will give information to assess the hazard which, combined with the exposure assessment, will form the basis for the risk characterisation. The absorption, distribution, metabolism and excretion (ADME) parameters are likely to be influenced by both the chemical composition of the ENM as well as its physico-chemical properties (e.g. size, shape, solubility, surface charge and surface reactivity).
Prior to commencing the detailed risk assessment of the nanomaterial, anticipated exposure scenarios from the proposed uses should be outlined. These exposure scenarios will contribute to decisions on the extent of the hazard characterisation and will provide parameters for the exposure assessment required in risk assessment.
Six cases are presented which outline different toxicity testing approaches. Where convincing evidence is provided indicating that ENM use does not result in presence of the ENM or its degradation/solubilisation products in the food/feed then there is no need for any additional testing. When transformation of the ENM into a non-nanoform in the food/feed matrix is judged to be complete before ingestion, then EFSA guidance for non-nanoforms for the specific intended use should be applied. When it can be demonstrated that an ENM completely dissolves/degrades in the gastro-intestinal tract without absorption of the ENM, the hazard identification and hazard characterisation can rely on data for the non-nanoform substance (if available). When information on a non-nanoform of the same substance is available and where some or all of the ENM persists in the food/feed matrix and in gastrointestinal fluids, a testing approach is recommended which is based on comparing information on ADME, toxicity and genotoxicity of the non-nanoform with ADME , repeated-dose 90-day oral toxicity study and genotoxicity information of the ENM. When information on a non-nanoform is not available and where some or all of the ENM persists in the food/feed matrix and in gastrointestinal fluids, the approach for toxicity tests on the ENM should follow the relevant EFSA guidance for the intended use with the modifications in the present ENM Guidance to take into account the nanoproperties.
Appropriate in vitro and in vivo studies on the ENM should be undertaken to identify hazards and obtain dose-response data to characterise the hazards. Some test models and standard testing protocols used for non-nanoform substances may not necessarily be appropriate or optimal for the testing of ENM, and ongoing efforts in the research community are currently addressing these issues.
The starting point for determining the amount of ENM for the exposure assessment currently has to rely on information on the material added to food/feed or that is in contact with food/feed. The initial characteristics of the added ENM can be used as an assumption in the exposure assessment, but it is preferable to determine the amount of the ENM present in the food/feed matrix. Currently it is not possible to routinely determine ENM in situ in the food or feed matrix, which increases the uncertainty in the exposure assessment. In the absence of exposure data, and where it is not possible to determine the nanoform in the food/feed matrix, it should be assumed that all added ENM, is present, ingested and absorbed as the nanoform, although the structure/properties of the ENM remain undetermined and difficult to relate to the structure/properties of the ENM used in the toxicity studies.
There are currently uncertainties related to the identification, characterisation and detection of ENM that are related to the lack of suitable and validated test methods to cover all possible applications, aspects and properties of ENM. Similarly, there are a number of uncertainties related to the applicability of current standard biological and toxicological testing methods to ENM. For these reasons, this ENM Guidance will need to be updated based on experience and acquired knowledge. It is acknowledged that the field is under fast development, and consequently this guidance document will be revised as appropriate.