Non-intentionally added substances (NIAS) are chemical compounds that are unintentionally included in a product.
NIAS are substances that may be present as a result of manufacturing processes, side reactions, contaminations or migrations from other materials.
Identification and assessment of NIAS is key to ensure the safety and quality of materials used in many sensitive industries and applications, such as food or medical products, where safety and compliance with strict regulations is crucial.
Commission Regulation (EU) No. 10/2011 on plastic materials and articles intended to come into contact with food introduces the concept of non-intentionally added substances (NIAS). Preambles 18 and 20 mention the presence of NIAS, given that substances used in the manufacture of plastic materials may contain impurities originating from their manufacturing or extraction process, and that, during the manufacture and use of plastic materials and articles, reaction and degradation products can be formed.
The different NIAS described, which may be present in different materials, should be assessed by the manufacturer in accordance with internationally recognized scientific principles on risk assessment.
What is a NIAS screening?
With no standardized protocol, the assessment of NIAS in food contact materials is carried out following the recommendations of some international guidelines such as those published by the International Life Sciences Institute (ILSI) in 2015 and 2023.
The phases of the study include the identification of NIAS by chromatographic techniques and their risk assessment by calculating exposure and assessing NIAS toxicity.
Sample preparation can be performed by migration tests using food simulants or under worst-case conditions by simulating a total migration of the NIAS present through solvent extraction. The selection of the technique depends on the aim of the study and client needs. The analytical techniques used for identification vary depending on the nature of the NIAS, although gas chromatography coupled with mass spectrometry (GC-MS) is commonly used for volatile and semi-volatile substances and liquid chromatography coupled with mass spectrometry (LC-MS) is used for non-volatile compounds.
Once the migrating substances in the sample have been identified, the toxicity of each one is evaluated. This estimation can be carried out using two complementary techniques:
- In silico tools: They are based on computational methods that compare the compound of interest with structurally similar compounds for which toxicity studies are available.
- Experimental tools such as in vitro bioassays: They can be very useful for compounds that cannot be correctly identified or to provide additional information on complex mixtures.
The final step in the NIAS study is risk assessment. A bibliographic review is first carried out to see if the substance to be assessed is covered by legislation or whether studies on its toxicity are available. If not, the threshold of toxicological concern (TTC) based on Cramer Classes is used, which assumes that there is a level of exposure below which no significant risks are expected to occur.
Types of tests
- Predicted NIAS: In the early stages of the processing chain, more information is available about the composition and reaction products of the materials. Therefore, predicted NIAS can be detected using targeted screening methods. A typical example is the presence of primary aromatic amines (PAAs), which may be cleavage products of azo pigments, may appear as impurities in dyes or may be formed by the hydrolysis of aromatic isocyanates. Another example are some metals that are not authorized for use in plastic materials but may be present as impurities and therefore must be monitored. Other substances, such as acetaldehyde and formaldehyde, can be byproducts of the manufacture of PET resins and are listed in Annex I of Regulation (EU) No. 10/2011 with their relevant specific migration limit.
- Unpredicted NIAS: For assessment of final articles, non-targeted screening methods are often used to try to identify as many unpredicted NIAS as possible. In this case, analysis is carried out using GC and LC techniques combined with high-resolution mass spectrometry to detect as many substances at very low concentrations as possible.
If we know the potential migration of the substances to food, the daily intake can be estimated so that a toxicological assessment can be performed, and the health risk posed by the detected substances can be characterized.
NIAS and the circular economy
The presence of recycled materials in packaging and articles intended to come into contact with food is part of the circular economy solution. Improved waste sorting systems, as well as increasingly sophisticated recycling processes and the banning of certain substances and groups of substances prevent NIAS from being introduced into the recycling system through cross-contamination and accumulation.
AIMPLAS provides NIAS assessment based on a global vision that includes:
- Review of declarations of conformity of materials
- Selection of test conditions
- Targeted screening for NIAS (e.g. PAAs, metals, listed substances)
- Non-targeted screening for NIAS using high-resolution equipment
- Preliminary toxicological assessment using in silico tools
- In vitro bioassays
Although it is the responsibility of the final manufacturer to verify the suitability of the material intended to come into contact with food, in the case of the presence of NIAS, it is essential for tests to be carried out in the upstream stages of the processing chain to be able to pass on information about NIAS that may be produced or added during their manufacturing processes (e.g. oligomers, contaminants), printing (set-off), gluing and other procedures.
NIAS can occur throughout the packaging manufacturing chain and it is therefore necessary to assess the presence of substances that have been produced in the final stage of theprocess, given that transformations may generate new NIAS or remove them from previous products, as in the case of volatile organic compounds.
Migration tests provide more realistic concentration values by simulating the actual application of packaging. However, these tests are more expensive and may not provide much information in intermediate stages of the packaging conversion process.
Worst-case calculations, which assume a total migration of NIAS scenario, are faster and help estimate all possible NIAS likely to migrate without the need for additional steps. On the other hand, they may overestimate migration when performed on a final product.