APROBA-Plus: A probabilistic tool to evaluate and express uncertainty in hazard characterization and exposure assessment of substances

Abstract

To facilitate the application of probabilistic risk assessment, the WHO released the APROBA tool. This tool applies lognormal uncertainty distributions to the different aspects of the hazard characterization, resulting in a probabilistic health-based guidance value. The current paper describes an extension, APROBA-Plus, which combines the output from the probabilistic hazard characterization with the probabilistic exposure to rapidly characterize risk and its uncertainty. The uncertainty in exposure is graphically compared with the uncertainty in the target human dose, i.e. the dose that complies with the specified protection goals. APROBA-Plus is applied to several case studies, resulting in distinct outcomes and illustrating that APROBA-Plus could serve as a standard extension of routine risk assessments. By visualizing the uncertainties, APROBA-Plus provides a more transparent and informative outcome than the more usual deterministic approaches, so that risk managers can make better informed decisions. For example, APROBA-Plus can help in deciding whether risk-reducing measures are warranted or that a refined risk assessment would first be needed. If the latter, the tool can be used to prioritize possible refinements. APROBA-Plus may also be used to rank substances into different risk categories, based on potential health risks without being compromised by different levels of conservatism that may be associated with point estimates of risk.

Keywords: Communicating uncertainty; Exposure assessment; Probabilistic risk assessment.

Figure 1

Hypothetical example of an APROBA-Plus graph. In this example, the incidence goal related to the HD_M^I is 1%, and the exposure estimate relates to the 95^th percentile of the adult population (see legend). See text for further explanation.

Figure 2

Comparison of nivalenol’s HD_M^I relating to an incidence goal of 1% and the 95^th percentile exposure of toddlers (black, ellipse on right hand side) and adults (blue) in APROBA-Plus. The blue diamond and black triangle indicate the risk based on the deterministic RfD (of 1.2 µg/kg bw/day) and reported upper confidence limits of exposure of adults and toddlers respectively.

Figure 3

Comparison of HD_M^I (I=1% and M=5%) and exposure for the two other illustrative examples (tropane alkaloids, left panel, and Allura Red, right panel) in the APROBA-Plus analysis. In the right plot the two ellipses relate to two subpopulations, in the left plot to two different data sources. The blue diamonds and black triangles indicate the risk ratios of these compounds. For more details, see Supplemental Material.

Figure 4

Illustration of the additional information from APROBA-Plus as compared to a deterministic risk assessment which are indicated by the marks (triangle, diamond). The deterministic risk ratio in both cases is close to unity (see diamonds) and would be regarded as “ties” in risk ranking. However, the ellipse for novaluron (right plot) extends further into the green area than for imidacloprid (left plot), implying that there is a considerable chance that the distance between exposure and target human dose is greater for novaluron than for imidacloprid. Thus, with the probabilistic approach risk ranking is possible in this case.