Update: use of the benchmark dose approach in risk assessment

Hardy, Anthony and Benford, Diane and Halldorsson, Thorhallur and Jeger, Michael John and Knutsen, Katrine Helle and More, Simon and Mortensen, Alicja and Naegeli, Hanspeter and Noteborn, Hubert and Ockleford, Colin and Ricci, Antonia and Rychen, Guido and Silano, Vittorio and Solecki, Roland and Turck, Dominique and Aerts, Marc and Bodin, Laurent and Davis, Allen and Edler, Lutz and Gundert-Remy, Ursula and Sand, Salomon and Slob, Wout and Bottex, Bernard and Abrahantes, Jose Cortiñas and Marques, Daniele Court and Kass, George and Schlatter, Josef R. (2017) Update: use of the benchmark dose approach in risk assessment. EFSA Journal, 15 (1): 04658. ISSN 1831-4732

Abstract

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.