3.2.3. Confidence assessment of OBLs

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3. Use of PBK* modelling to estimate biomarker levels from external intake.

4. Use of simple approaches, such as the urinary mass balance approach to calculate corresponding biomarker levels for PODs* (NOAELs* etc.), and applying assessment factors to account for uncertainties. (see chapter 3.3) PBK* needs to cover all relevant exposure pathways (inhalation, skin uptake, and ingestion) and should predict the urinary biomarker excretion concentrations as well as central compartment (blood) concentrations. PBK* models should as far as possible incorporate human parameters and be adjusted or calibrated with human data. PODs* relevance and reliability Urinary fraction data Confidence assessment

3.2.3. Confidence assessment of OBLs*

The confidence of the OBL* derivation needs to be assessed to allow appropriate risk-management. Confidence assessments have been applied in HBM4EU guidance value setting and in WHO/ICPS, ANSES, US-EPA, and Health Canada when setting limit values for the general population. Confidence assessment within HBM4EU has been described by (Apel et al., 2020). The level of confidence is considered in the following aspects for both occupationally exposed adults and the general population:

 nature and quality of the data  choice of the critical effect and the mode of action  key study  critical dose & point of departure (POD*)  extrapolations across and within species

In addition, HBM4EU (Apel et al., 2020) also highlights two main elements described earlier for assessing the confidence in the Biomonitoring Equivalent (BE*) values:

Understanding of the relationship between the measured biomarker and the critical or relevant target tissue dose metric; and robustness of the available toxicokinetic models and data.

The first five aspects are very much related to the general uncertainties related to the hazard and doseresponse assessment and apply to any limit values (i.e., are not specific for OBLs*). Only the two latter aspects (1, 2) are specific for the OBL setting. The OECD working group considered that more emphasis could be put on aspects specific for the OBL* setting. One of the main issues highlighted by the OECD working group was whether deriving an OBL* (instead of an OEL*or OELV*) will or will not bring significant additional uncertainty to the overall uncertainties already caused by the uncertainties related to the hazard data. Thus, the OECD working group proposes to use three main aspects when assessing uncertainties:

Table 6. Confidence assessment categories for OBL*derivations

1st confidence category 2nd confidence category

3rd confidence category

Hazard and dose-response assessment, selection of POD*

Selection of biomarker (covering aspects related to the specificity and sensitivity of the biomarker, and e.g., analytical aspects including the likelihood of pre-analytical errors (like confounding exposure sources, contamination) Toxicokinetic aspects, including excretion kinetics; quality & robustness of the toxicokinetic data, quality & robustness of the established correlations between external and internal levels or correlations between toxicological effects and biomarker levels, urinary fraction data

OCCUPATIONAL BIOMONITORING GUIDANCE DOCUMENT © OECD 2022