|1.||Definition and types of NIAS|
|2.||Analytical methods and risk assessment|
1. Definition and types of NIAS
Non-intentionally added substances (NIAS) are chemical compounds that are present in a material but have not been added for a technical reason during the production process. Their presence in food contact materials (FCM) is generally not known by the consumer and often is a challenge for the FCM producer. NIAS originate from break-down products of food contact materials, impurities of starting materials, unwanted side-products and various contaminants from recycling processes (Figure 1). Generally, it is accepted that only compounds <1000 Da are considered NIAS, because substances with a higher molecular weight are regarded as inert towards migration due to their larger size.
Break-down products may originate from both the polymers and the additives. Break-down processes may occur during manufacture processing, storage and/or in contact with the food itself. The properties of certain food types may for example initiate the hydrolysis of BADGE to BADGE∙2H2O in the food . Raw materials and additives used in the production of FCMs often contain impurities. Major impurities are generally known by the producer, but minor impurities may remain unknown . Nevertheless the supplier has to guarantee the safety of the final product (Art. 3, Framework Regulation EC 1935/2004). Side products may be created, as FCMs are produced in several steps and contain additives such as antioxidants, UV protectors, adhesives and dyes. Side-reactions occur during each of these production steps, many of which are difficult to predict and can form novel reaction by-products. Finally, contaminants may arise from recycling processes. They originate from non-food contact recycled material, the previously packaged food, and/or misuse of the packaging before recycling [3, 4]. Materials intended for recycling, such as paper and board, PET and polyolefins [5, 6], generally contain additives, dyes, adhesives and NIAS that also enter the recycling process. The mixtures of chemicals present during recycling can react and form new unwanted compounds. Furthermore, accumulation of chemicals might play a role when materials are recycled several times. The identification and management of NIAS in recycled materials is a particular challenge because of the difficulty in tracing their origin.
2. Analytical Methods and Risk Assessment
When investigating the NIAS of a FCM, usually not all compounds of interest can be detected with state-of-the-art analytical techniques (Figure 2).
The analysis of NIAS is complicated by the lack of knowledge concerning the chemical properties of unidentified substances. Extracted samples can be separated chromatographically and analyzed by mass spectrometry. As in many chemical analyses, sample extraction is one of the most crucial steps, because incomplete transfer hinders full analysis. Furthermore, new mass spectra might not be assigned to a known chemical structure. Applying direct thermal desorption techniques prevent the extraction step, but the results are even more difficult to interpret due to complicated fragmentation patterns. Finally, knowledge about the concentrations of NIAS is needed to carry out risk assessment. However, often analytical standards are missing and the use of internal standards for quantification results in high uncertainties .
The risk assessment of NIAS may either be done using the classical approach which entails the screening of migrates, the identification of unknowns, and their subsequent toxicological evaluation. This procedure is very complex and expensive. Furthermore, it is simply not applicable for substances that cannot be identified by current analytical techniques or produced in sufficient amounts for toxicological testing. Alternatively, the whole migrate may be examined in bioassays for specific toxicological endpoints. However, this method does not generate knowledge about specific substances and results may change from whole migrate batch to batch. Thirdly, applying the Threshold of Toxicological Concern (TTC) to NIAS has been suggested. Human exposure thresholds that have a very low probability of causing adverse health effects could be assigned to those NIAS with known chemical structures, according to recent recommendations on the application of the TTC . By contrast, NIAS with unknown chemical structures have to be proven not to be carcinogenic, mutagenic, reprotoxic (CMR) or bioaccumulative and must not exceed an exposure level of 90 μg/person/day. This task might be achieved by applying suitable chromatographic techniques, sample preparation and/or detection methods . A combination of these risk assessments might help to decrease the uncertainties of each single method.
In the coming years, the detection and identification of NIAS will become easier due to advances in analytical techniques and growing databases. However, many open questions have to be answered: Is it necessary to perform the classical approach including full identification and toxicological tests of all detected substances? Should the TTC concept be adopted to evaluate the safety on NIAS? Are bioassays with the migrates necessary to cover possibly hazardous substances that are either not detected at all or lie below the threshold and do not give a structural alert? Should intermediate and/or tiered approaches be developed? For all concepts, a better information transfer through the whole value chain would largely facilitate the identification of unknown compounds.
It is in accordance with the current European legislation that also non-authorized substances are present in FCMs when they are non-intentionally added (EC 10/2011), but the FCM manufacturer is obliged to ensure NIAS safety, according to the Framework Regulation EC 1935/2004, Art. 3 and the Plastics Regulation EC 10/2011, Art. 19. Consequently, the safety of NIAS has to be assessed. At the moment, no levels of migration or exposure are set for which compliance with this requirement can be demonstrated. As specified in EC 10/2011, unauthorized substances may be used in FCM plastics, provided they do not migrate at levels above 10 µg/kg food. Therefore, in practice a threshold of 10 µg/kg food is used for NIAS. Substances that are known CMRs or have nanomaterial properties are excluded from this practice.
In the United States substances that have been shown to result in, or are expected to result in dietary concentrations at or below 0.5 ppb, have not been shown to be carcinogenic and have no other health or safety concern are exempted from authorization as an indirect food additive (21 C.F.R. §170.39). Theoretically, NIAS could be regulated accordingly, but their presence, concentrations and some basic information on the structure and toxicity have to be provided to fulfill these requirements. Furthermore, FDA specifically exempts impurities of indirect food additives from the Delaney Clause which prohibits the presence of carcinogens in food .
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