Harmonisation et complémentarité des méthodes de criblage non ciblées dans le contexte de l'exposition professionnelle : leçons tirées d'une vaste étude interlaboratoire de l'UE

Occupational exposure to chemicals poses major challenges for risk assessment and regulatory decision-making. Innovative approaches based on suspect and non-targeted screening (NTS) using high-resolution mass spectrometry (HRMS) have emerged as a promising solution. As part of the European Partnership for the Assessment of Risks from Chemicals (PARC), a project has been launched to conduct a proof of concept study of NTS methods across multiple European laboratories. The first phase involved an interlaboratory study to assess comparability, coverage and complementarity between partners' methods. This activity will support further evaluation of workers' exposure in waste management and healthcare sectors under the PARC project. A quality control mixture of 80 standards was developed to include chemicals commonly found in the environment and in workers from waste management and healthcare sectors. Urine samples (low, medium, high specific gravity: LSG, MSG, HSG) and plasma were spiked with the QA/QC mix at 0, 5, 20, and 100ng/mL, and analyzed by 12 partners using their own sample preparation and LC-HRMS and/or GC-HRMS methods. Comparison was based on the number of substances detected and the assigned identification levels (ID). Preliminary findings revealed variability in detection limits influenced by substance polarity, volatility, and analytical methods used by partners (Figure 1). Despite these differences, consistent detection across laboratories demonstrated the complementarity of approaches and validated the NTS proof of concept for multi-exposure screening. Urine samples with LSG yielded the highest number of detected substances and Level 1 identifications across most methods. Detection rates and identification levels increased with dose, irrespective of urine specific gravity. Reported identification levels varied among partners, despite all receiving the same QA/QC mix with standards, underscoring the need for adherence to ID level guidelines in reporting. The study confirms NTS as a valid approach for screening multiple chemicals in workers, with complementary methods across European labs enhancing comparability. Matrix effects highlight the need for careful preparation, while variability in ID levels stresses the importance of harmonized reporting. Standardizing NTS is key to improving exposure assessment and supporting regulatory decisions in Europe.

Figure 1: Number of substances detected per urine and blood sample for each dose (0, 5, 20, and 100ng/mL) across laboratories, with associated reported identification levels.