TY - JOUR

T1 - Opinion on the impact of non-monotonic dose responses on EFSA′s human health risk assessments

AU - EFSA Scientific Committee, null

AU - More, Simon John

AU - Benford, Diane

AU - Hougaard Bennekou, Susanne

AU - Bampidis, Vasileios

AU - Bragard, Claude

AU - Halldorsson, Thorhallur I

AU - Hernández-Jerez, Antonio F

AU - Koutsoumanis, Kostas P

AU - Lambré, Claude

AU - Machera, Kyriaki

AU - Mullins, Ewen

AU - Nielsen, Søren Saxmose

AU - Schlatter, Josef Rudolf

AU - Schrenk, Dieter

AU - Turck, Dominique

AU - Tarazona, Jose

AU - Younes, Maged

N1 - © 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

PY - 2021/10/21

Y1 - 2021/10/21

N2 - Abstract 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.

AB - Abstract 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.

KW - non-monotonic dose response (NMDR)

KW - statistical analysis

KW - probabilistic analysis

KW - biological relevance

KW - reference dose

KW - human health risk assessment

U2 - 10.2903/j.efsa.2021.6877

DO - 10.2903/j.efsa.2021.6877

M3 - Journal article

C2 - 34712366

VL - 19

JO - E F S A Journal

JF - E F S A Journal

SN - 1831-4732

IS - 10

M1 - e06877

ER -