Update: use of the benchmark dose approach in risk assessment

Abstract

The Scientific Committee (SC) reconfirms that the benchmark dose (BMD) approach is a scientifically more advanced method compared to the NOAEL approach for deriving a Reference Point (RP). Most of the modifications made to the SC guidance of 2009 concern the section providing guidance on how to apply the BMD approach. Model averaging is recommended as the preferred method for calculating the BMD confidence interval, while acknowledging that the respective tools are still under development and may not be easily accessible to all. Therefore, selecting or rejecting models is still considered as a suboptimal alternative. The set of default models to be used for BMD analysis has been reviewed, and the Akaike information criterion (AIC) has been introduced instead of the log-likelihood to characterise the goodness of fit of different mathematical models to a dose-response data set. A flowchart has also been inserted in this update to guide the reader step-by-step when performing a BMD analysis, as well as a chapter on the distributional part of dose-response models and a template for reporting a BMD analysis in a complete and transparent manner. Finally, it is recommended to always report the BMD confidence interval rather than the value of the BMD. The lower bound (BMDL) is needed as a potential RP, and the upper bound (BMDU) is needed for establishing the BMDU/BMDL per ratio reflecting the uncertainty in the BMD estimate. This updated guidance does not call for a general re-evaluation of previous assessments where the NOAEL approach or the BMD approach as described in the 2009 SC guidance was used, in particular when the exposure is clearly smaller (e.g. more than one order of magnitude) than the health-based guidance value. Finally, the SC firmly reiterates to reconsider test guidelines given the expected wide application of the BMD approach.

Risks for human health related to the presence of pyrrolizidine alkaloids in honey, tea, herbal infusions and food supplements

“…The CONTAM Panel agreed that an update of the dose response analysis performed for the chronic effects of PAs in the previous opinion is warranted in view of the updated guidance of the EFSA Scientific Committee on the use of benchmark modelling in risk assessment (EFSA Scientific Committee, 2017).…”

EFSA Scientific Colloquium 23 – Joint European Food Safety Authority and Evidence‐Based Toxicology Collaboration Colloquium Evidence integration in risk assessment: the science of combining apples and oranges 25–26 October 2017 Lisbon, Portugal

“…After introducing some illustrative examples, the guidelines regarding the current practice for a single end-point and a single study and their extension to multiple settings, as provided by the Update: EFSA Scientific Committee Guidance on the use of the benchmark dose approach in risk assessment (EFSA Scientific Committee et al, 2017c) and by US EPA Benchmark Dose Technical Guidance (US EPA, 2012), were briefly discussed. After introducing some illustrative examples, the guidelines regarding the current practice for a single end-point and a single study and their extension to multiple settings, as provided by the Update: EFSA Scientific Committee Guidance on the use of the benchmark dose approach in risk assessment (EFSA Scientific Committee et al, 2017c) and by US EPA Benchmark Dose Technical Guidance (US EPA, 2012), were briefly discussed.…”

Appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms

“…The dose‐dependent incidences of emesis upon administration of T2 and HT2 in mink in the study from Wu et al. () has been selected for derivation of a BMD for T2 and HT2 by applying expert knowledge and following the new EFSA guidance on the use of the BMD (EFSA Scientific Committee, ). The findings selected for deriving a BMD are described extensively in Sections 8, 11 and 13 of this opinion.…”