3.3.5. Limitations, uncertainties and confidence assessment of POBL

38 

HDI* 0.93 - 2.79 µg/L 15 µg/L## Aluminium 1.38 - 9.2 µg/L 57 µg/L Chromium 0.76 µg/L 2.5 - 10 µg/L

# Available in: DOI: 10.1002/3527600418.bb11781e2319 ## Available in (German BAT derivation for HDI, 2011)

Conclusion

5-16 6-41 3-13

The results show that the POBL* derivations were sufficiently sensitive (3 to 41 times more sensitive) in all four case studies to identify potential toxicological risks compared to the refined OBLs* and existing BLVs*. Using a POBL* can lead to risk identification, but we recommend always checking if a refined OBL* can be derived (see chapter 5.5). This will also need a final confidence and reliability assessment (see chapter 3.2.3). This can lead to refined OBL* derivations or improved risk. management options. We recommend deriving POBL* using the urinary mass balance approach as a screening method when relevant POD*s and urinary excretion factor data are available. This limits the use of additional safety factors. In cases where a POBL* is lower than a ROBL*, the POBL* should be set equal to ROBL* for this region to avoid an overestimation of risks.

3.3.5. Limitations, uncertainties and confidence assessment of POBL*

The primary purpose of the POBL* is screening and health-risk identification. The POBL* can lead in some cases to an overestimation of toxicological risks compared to a refined OBL*, as shown by the sensitivity analysis results (Table 11). Therefore, after identifying risk, the potential for derivation of an OBL* should be checked (see chapter 5.5). Nevertheless, the urinary mass balance approach (adapted from Apel et al. (2020) can in principle be used for deriving refined OBLs*. In this case, a medium or high confidence level needs to be assessed for the related PODs* on toxicology and urinary fraction data. A confidence assessment scheme is generally suggested for the refined OBL* derivation (see chapter 3.2.3). The primary limitations and uncertainties in the urinary mass balance approach are related to the quality and confidence assessment of:

 Hazard and dose-response assessments, selection of POD* (see case study scenarios Tables 8-11)  Urinary fraction data (should be based on a steady-state concentration)  Toxicokinetic knowledge for investigated substances

An experienced toxicologist or risk-assessor needs to assess the validity and limitation of the relevant data.

If relevant experimental data are absent, modeling can be helpful. PBK *modeling can help identify target organ peak concentration as the metric for organ toxicity, which can be compared to NOAEL data from toxicity studies. PBK* modelling can simulate inhalation and skin exposures as well as oral intake separately, which will give an understanding of the major route of exposure. This can then be used in designing risk management strategies. PBK* modelling is useful in reaching scientifically sound regulatory decisions, but it still needs to reach regulatory acceptance in many fields. (more information on PBK* is available in chapter 6.5).

OCCUPATIONAL BIOMONITORING GUIDANCE DOCUMENT © OECD 2022