RT Journal Article
T1 Opinion on the impact of non-monotonic dose responses on EFSA's human health risk assessments.
A1 EFSA Scientific Committee, 
A1 More, Simon
A1 Benford, Diane
A1 Hougaard Bennekou, Susanne
A1 Bampidis, Vasileios
A1 Bragard, Claude
A1 Halldorsson, Thorhallur
A1 Hernandez-Jerez, Antonio
A1 Koutsoumanis, Kostas
A1 Lambré, Claude
A1 Machera, Kyriaki
A1 Mullins, Ewen
A1 Nielsen, Søren Saxmose
A1 Schlatter, Josef
A1 Schrenk, Dieter
A1 Turck, Dominique
A1 Tarazona, Jose
A1 Younes, Maged
K1 biological relevance
K1 human health risk assessment
K1 non‐monotonic dose response (NMDR)
K1 probabilistic analysis
K1 reference dose
K1 statistical analysis
AB This Opinion assesses the biological relevance of the non-monotonic dose responses (NMDR) identified in a previous EFSA External Report (Beausoleil et al., 2016) produced under GP/EFSA/SCER/2014/01 and the follow-up probabilistic assessment (Chevillotte et al., 2017a,b), focusing on the in vivo data sets fulfilling most of the checkpoints of the visual/statistical-based analysis identified in Beausoleil et al. (2016). The evaluation was completed with cases discussed in EFSA assessments and the update of the scientific literature. Observations of NMDR were confirmed in certain studies and are particularly relevant for receptor-mediated effects. Based on the results of the evaluation, the Opinion proposes an approach to be applied during the risk assessment process when apparent non-monotonicity is observed, also providing advice on specific elements to be considered to facilitate the assessment of NMDR in EFSA risk assessments. The proposed approach was applied to two case studies, Bisphenol A and bis(2-ethylhexyl phthalate (DEHP) and these evaluations are reported in dedicated annexes. Considering the potential impact of NMDRs in regulatory risk assessment, the Scientific Committee recommends a concerted international effort on developing internationally agreed guidance and harmonised frameworks for identifying and addressing NMDRs in the risk assessment process.
YR 2021
FD 2021-10-20
LK https://hdl.handle.net/10668/26743
UL https://hdl.handle.net/10668/26743
LA en
DS RISalud
RD Apr 5, 2025