Guidance on the use of the benchmark dose approach in risk assessment
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Guidance on the use of the benchmark dose approach in risk assessment. / EFSA Scientific Committee; More, Simon John; Bampidis, Vasileios; Benford, Diane; Bragard, Claude; Halldorsson, Thorhallur Ingi; Hernández-Jerez, Antonio F; Bennekou, Susanne Hougaard; Koutsoumanis, Kostas; Lambré, Claude; Machera, Kyriaki; Mennes, Wim; Mullins, Ewen; Nielsen, Søren Saxmose; Schrenk, Dieter; Turck, Dominique; Younes, Maged; Aerts, Marc; Edler, Lutz; Sand, Salomon; Wright, Matthew; Binaglia, Marco; Bottex, Bernard; Abrahantes, Jose Cortiñas; Schlatter, Josef.
In: EFSA Journal, Vol. 20, No. 10, e07584, 2022, p. 1-67.Research output: Contribution to journal › Journal article › Research
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TY - JOUR
T1 - Guidance on the use of the benchmark dose approach in risk assessment
AU - EFSA Scientific Committee, null
AU - More, Simon John
AU - Bampidis, Vasileios
AU - Benford, Diane
AU - Bragard, Claude
AU - Halldorsson, Thorhallur Ingi
AU - Hernández-Jerez, Antonio F
AU - Bennekou, Susanne Hougaard
AU - Koutsoumanis, Kostas
AU - Lambré, Claude
AU - Machera, Kyriaki
AU - Mennes, Wim
AU - Mullins, Ewen
AU - Nielsen, Søren Saxmose
AU - Schrenk, Dieter
AU - Turck, Dominique
AU - Younes, Maged
AU - Aerts, Marc
AU - Edler, Lutz
AU - Sand, Salomon
AU - Wright, Matthew
AU - Binaglia, Marco
AU - Bottex, Bernard
AU - Abrahantes, Jose Cortiñas
AU - Schlatter, Josef
PY - 2022
Y1 - 2022
N2 - Abstract The Scientific Committee (SC) reconfirms that the benchmark dose (BMD) approach is a scientifically more advanced method compared to the no-observed-adverse-effect-level (NOAEL) approach for deriving a Reference Point (RP). The major change compared to the previous Guidance (EFSA SC, 2017) concerns the Section 2.5, in which a change from the frequentist to the Bayesian paradigm is recommended. In the former, uncertainty about the unknown parameters is measured by confidence and significance levels, interpreted and calibrated under hypothetical repetition, while probability distributions are attached to the unknown parameters in the Bayesian approach, and the notion of probability is extended to reflect uncertainty of knowledge. In addition, the Bayesian approach can mimic a learning process and reflects the accumulation of knowledge over time. Model averaging is again recommended as the preferred method for estimating the BMD and calculating its credible interval. The set of default models to be used for BMD analysis has been reviewed and amended so that there is now a single set of models for quantal and continuous data. The flow chart guiding the reader step-by-step when performing a BMD analysis has also been updated, and a chapter comparing the frequentist to the Bayesian paradigm inserted. Also, when using Bayesian BMD modelling, the lower bound (BMDL) is to be considered as potential RP, and the upper bound (BMDU) is needed for establishing the BMDU/BMDL 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 or 2017 Guidance was used, in particular when the exposure is clearly lower (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 wide application of the BMD approach.
AB - Abstract The Scientific Committee (SC) reconfirms that the benchmark dose (BMD) approach is a scientifically more advanced method compared to the no-observed-adverse-effect-level (NOAEL) approach for deriving a Reference Point (RP). The major change compared to the previous Guidance (EFSA SC, 2017) concerns the Section 2.5, in which a change from the frequentist to the Bayesian paradigm is recommended. In the former, uncertainty about the unknown parameters is measured by confidence and significance levels, interpreted and calibrated under hypothetical repetition, while probability distributions are attached to the unknown parameters in the Bayesian approach, and the notion of probability is extended to reflect uncertainty of knowledge. In addition, the Bayesian approach can mimic a learning process and reflects the accumulation of knowledge over time. Model averaging is again recommended as the preferred method for estimating the BMD and calculating its credible interval. The set of default models to be used for BMD analysis has been reviewed and amended so that there is now a single set of models for quantal and continuous data. The flow chart guiding the reader step-by-step when performing a BMD analysis has also been updated, and a chapter comparing the frequentist to the Bayesian paradigm inserted. Also, when using Bayesian BMD modelling, the lower bound (BMDL) is to be considered as potential RP, and the upper bound (BMDU) is needed for establishing the BMDU/BMDL 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 or 2017 Guidance was used, in particular when the exposure is clearly lower (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 wide application of the BMD approach.
KW - BMD
KW - BMDL
KW - benchmark response
KW - NOAEL
KW - dose–response modelling
KW - BMD software
KW - Bayesian model averaging
U2 - 10.2903/j.efsa.2022.7584
DO - 10.2903/j.efsa.2022.7584
M3 - Journal article
C2 - 36304832
VL - 20
SP - 1
EP - 67
JO - E F S A Journal
JF - E F S A Journal
SN - 1831-4732
IS - 10
M1 - e07584
ER -
ID: 324363774