Introduction: The NIAS concept and the regulatory context
Ensuring the chemical safety of packaging materials that come into contact with food is not limited to controlling substances intentionally added during the manufacturing process (Intentionally Added Substances - IAS). Article 3 of the Framework Regulation (EC) No 1935/2004 of the European Union and Regulation (EU) No 10/2011 on plastics materials oblige the manufacturers to unintentionally added substances (non-intentionally added Substances – NIAS) and conduct a risk assessment. Nias can come from contaminants in the starting materials, from reaction by-products, degradation products or environmental contaminants produced during production. With the introduction of the PPWR, this obligation has become even clearer, so that packaging manufacturers have to tackle the NIAS assessment with a systematic approach. Nano-Test Labor Services offer a comprehensive and GLP-compliant service portfolio in the area of NIAS assessment, ranging from screening and identification studies with advanced analysis techniques to toxicological risk assessment.
Definition, sources and classification of NIAS
NIAS is a broad term that encompasses all chemical substances that are not intentionally added to the formulation of a packaging material, but may be present in the final product. The sources of these substances are diverse and can arise throughout the entire lifecycle of the packaging. A correct understanding of NIAS is crucial for the development of an effective analysis strategy and the performance of a risk assessment.
Classification of NIAS sources
The following table systematically summarizes the most important mechanisms of formation, sources and typical examples for each source:
| NIAS source | Mechanism of formation | Typical NIAS examples |
|---|---|---|
| Contaminations in the starting materials | Residues from the manufacturing process of monomers, additives or residues of solvents originating from the production process | Monomer isomers, solvent residues, catalyst residues, contaminations in chemicals of technical quality |
| Reaction by-products | Undesired compounds formed during polymerization, cross-linking or curing reactions undesired compounds | Oligomers (dimers, trimers), polymerization by-products, degradation products |
| Decomposition products | Thermal, photochemical or hydrolytic degradation of the polymer or additives | Degradation products of antioxidants, degradation products of UV stabilizers, depolymerization oligomers |
| Contaminations from recycling</ strong> | Foreign substances that enter the recycled raw material or residues from previous use | Printing ink components, adhesive residues, residues of previous products, MOSH/MOAH |
| Environmental contaminants | Substances that occur during production, storage or transport from the environment | PAH (polycyclic aromatic hydrocarbons), PCB, pesticide residues |
Note: The scope of the NIAS assessment is determined on a case-by-case basis based on the composition of the packaging material, the manufacturing process and the intended conditions of use. The guidelines published by the EFSA provide the basic methodological framework for the NIAS assessment.
Analytical strategy in NIAS assessment
The NIAS assessment represents one of the most complex areas of analytical chemistry due to the need to screen and identify a variety of known and unknown substances simultaneously. In the Nano-Test laboratory, the NIAS assessment is carried out using the following multi-stage and systematic approach.
Step-by-step NIAS assessment strategy
The NIAS assessment process applied by Nano-Test consists of four main phases, which are summarized in the following table:
| Phase | Step | Explanation |
|---|---|---|
| 1. Pre-evaluation and data collection | Review of information on formulation and manufacturing process | Theoretical determination of all raw materials, additives, production parameters, and potential NIAS sources (impurities, reaction by-products, decomposition products). In this phase, supplier declarations and safety data sheets (SDS) provided by the customer are also evaluated. |
| 2. Non-targeted screening (non-targeted screening) | Comprehensive screening using high-resolution mass spectrometry (HRMS) | The extract obtained after a suitable extraction and/or migration test is analyzed with LC-QTOF-MS and GC-QTOF-MS systems. The obtained data are evaluated with advanced data processing software to perform a library match and identify unknown peaks. |
| 3. Identification and semiquantitative determination | Structural elucidation of identified NIAS candidates | The structural characterization of unknown compounds is based on the exact mass obtained from the HRMS data, the isotope distribution and the MS/MS fragmentation pattern. As far as possible, validation is based on reference standards. The semi-quantitative estimate is based on an approach based on internal standards or structural analogues. |
| 4. Toxicological Risk Assessment | Evaluation of the identified NIAS with regard to food safety | For each identified NIAS, a risk assessment is performed using the EFSA's Threshold of Toxicological Concern (TTC) approach or substance-specific toxicological data. The Cramer classification and genotoxicity warnings (QSAR) are taken into account. |
Nano Test NIAS Analysis Platforms
The main analytical platforms used in the Nano Test Laboratory for the NIAS assessment, as well as their specific roles in NIAS analysis, are shown in the following table:
| Analytical Platform | Technical properties | Role in NIAS analysis | Target network profile |
|---|---|---|---|
| LC-QTOF-MS | High Resolution (‚30,000 FWHM), High Mass Accuracy (±3 ppm), MS/MS Fragmentation | Target-free screening and identification of polar and moderately polar NIAS | Oligomers, degradation products, antioxidants and their metabolites, plasticizers, lubricants |
| GC-QTOF-MS | High Resolution, Egg and Ci Ionization, Extensive Library (NIST, Wiley) | Targets Free Screening and Identification of Volatile and Semi-Flecked NIAS | Volatile organic compounds (VOCs), low molecular weight oligomers, solvent residues |
| LC-MS/MS (QQQ) | Triple-quadrupole, MRM mode, high selectivity and sensitivity | Targeted quantitative determination and validation of identified NIAS | Specific NIAS compounds (BPA, phthalates, PAA, etc.) |
| Headspace GC-MS | Headspace sampling, optimized for volatile connections | Screening and Quantification of Volatile NIAS | Residual monomers (styrene, butadiene), solvents, volatile degradation products |
Toxicological risk assessment and TTC approach
The ultimate goal of the NIAS assessment is to determine whether the identified substances pose a risk to consumer health. The “Threshold of Toxicological Concern” (TTC) approach adopted by EFSA offers a scientifically based risk assessment tool for substances whose structure is known but for which only limited toxicological data are available.
Nano Test uses the following systematic approach in this crucial phase of NIAS assessment:
Cramer Classification and TTC Thresholds
The following table summarizes the toxicological potential of the substances according to the Cramer classification system and the corresponding TTC thresholds:
| Cramer class | Toxicity potential | TTC threshold (μg/kg body weight/day) | Typical chemical structures |
|---|---|---|---|
| Class I | Low toxicity potential | 30 | Simple aliphatic hydrocarbons, normal metabolic products |
| Class II | Mean toxicity potential | 9 | Compounds with functional groups without aromatic rings, esters, ethers |
| Class III | High toxicity potential | 1, 5 | Aromatic compounds, heterocyclic structures, conjugated systems |
| Genotoxic substances | Suspected DNA-reactive genotoxicity | 0.0025 (for a lifetime risk of cancer of 1:10⁵) | Aflatoxin-like structures, N-nitroso compounds, DNA intercalators |
Note: EFSA does not recommend using the TTC approach for genotoxic carcinogens. Minimizing exposure (Alara principle) is of fundamental importance for such substances. In addition, the TTC approach may not be suitable for substance groups with potentially neurotoxic effects, such as organophosphates and carbamates.
Nano-Test's integrated NIAS assessment service
As Nano-Test Labor Services, we offer the NIAS assessment with a multidisciplinary and integrated approach. Our service model consists of the components summarized in the following table:
Nias Değerlendirmesi, Yalnızca Analitik Bir Test Değil, Aynı Zamanda Derinlemesine Bir Kimyasal Ve Toksilojik Uzmanlık straightened Çok Boyutlu bir Sureçtir. Nano-Test Olarak, Bu Sürecin Her Aşamasında, GLP Prensiplerine Bağlılık, Bilimsel Titizlik ve Müşteri Odaklı Danışmanlık Anlayışıyla Hareket etmekteyiz. The NIAS assessment is not only an analytical test, but a multi-layered process that requires well-founded chemical and toxicological expertise. As a nano test, at every stage of this process, we act in accordance with the GLP principles, scientific care and a customer-oriented approach to consulting. and to ensure that the relevant EU regulations are applied and to carry out their screening and risk assessment processes with a reliable partner, you can contact our team of experts for detailed information on Nano-Test's Nias Valuation Services.
| Service Component | Scope | Benefit for the customer |
|---|---|---|
| Formulation and Process Testing | Detailed investigation of the raw materials used, additives and the production process; Theoretical mapping of potential NIAS sources | The correct design of the analysis strategy, avoidance of unnecessary analyses |
| Target Independent Screening (HRMS) | Comprehensive, target-free chemical screening using LC-QTOF-MS and GC-QTOF-MS | Detection of unexpected contaminants and unknown NIAS |
| Structural lighting and half quantification | Structural characterization based on HRMS data and semi-quantitative estimate based on internal standards | Reliable identification of unknown peaks and determination of their approximate concentrations |
| Toxicological risk assessment | Comprehensive Risk Assessment Using TTC Approach, Cramer Classification and QSAR Toxicity Prediction (in Silico) | Scientifically based assessment of the food safety risk of defined NIAS |
| Report on compliance with regulatory regulations | Comprehensive report for the DOC (Declaration of Conformity), which contains all analytical results and the risk assessment | Full documentation for official applications and customer reviews |
In order to ensure the NIAS conformity of your packaging exported to the European market within the framework of the PPWR Regulation and the relevant EU legislation, and to conduct your procedures for targeted review and risk assessment together with a reliable partner, you can contact our team of experts for detailed information on the Get NIAS assessment services from Nano-Test.