3.5.4. Outlook and AOP-validated effect biomarker follow up

48 

specifically 100 Euro/samples for the majority of the effect biomarkers (twelve of sixteen). Six of sixteen effect biomarkers were assessed with very good sensitivity, specificity, and robustness. Many effect biomarkers have not been assessed due to the absence of data and missing reference compounds for their evaluation in terms of sensitivity and specificity.

Effect biomarker applications:

To make effective use of effect biomarkers, they need to be sufficiently characterized with regard to relevance, predictability of adversity, sensitivity, specificity and robustness. The questions outlined above can be used for this purpose. Furthermore, they should lead to a causal relationship with the combined occupational exposures of chemicals. We suggest using biomonitoring of effect biomarkers in a tiered approach and with similar terminology (ROBEL*, POBEL*, OBEL*) as for biomonitoring of exposure biomarkers (ROBL*, POBL*, OBL*). The tiered approach and proposed terminologies are briefly described in chapter 5.6 and 1.3.1.

We suggest reporting biomonitoring of effect biomarkers for Similar Exposure Groups (SEG*) to ensure a consistent interpretation of occupational exposure data and to avoid over-interpretation of individual results. This approach is analogous to (Technical Committee CEN 137, 2020) for Occupational Exposure Limits (OEL* or OELV*) and the SEG* can be applied with some small effect biomarker modifications provided in see chapter 9.2 in Annex B in Table B3. This will allow to identify with the SEG* where intervention is needed first.

3.5.4. Outlook and AOP-validated effect biomarker follow up

Validated effect biomarkers can be used to address mixture effects and many relevant health effect endpoints and adverse MoAs* in humans. Some are not yet covered under current chemical labelling and classification systems. Biomonitoring of effect biomarkers can be used to assess exposures to chemical mixtures of known and unknown sources. For most of the recommended effect biomarkers, we found a strong link to the growing Adverse Outcome Pathway (AOP*) knowledge. AOPs* describe chains of key events from a Molecular Initiating Events (MIE*) to Adverse Outcomes (AO). This knowledge offers a systematic understanding of effects that can be translated into regulatory use by defining relevant biological effect thresholds for relevant MoAs*. These thresholds need to be related to concentrations/levels of well-understood, prototypical stressors (focusing primarily on chemicals), that produce the MoA* effect. A need to derive mixture threshold levels (OBEL*) for well-characterized effect biomarkers was identified and in the International Society of Exposure Sciences (ISES) Europe HBM group (Zare Jeddi et al., 2021a, HBM4EU, 2021). Moreover, we recommend developing guiding principles for their derivation within WPHA/WPEA and OECD* Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST) in an interdisciplinary follow-up activity called: Using Adverse Outcome Pathways (AOP*) to address combined exposures to chemicals with relevant effect biomarkers. The follow up activity was adopted in 2021 and is briefly described in (Zare Jeddi et al. 2021b). A systematic understanding of both the relevance and interpretation of effect biomarker data will lead to increased protection for workers.

OCCUPATIONAL BIOMONITORING GUIDANCE DOCUMENT © OECD 2022