European Food Safety Authority’s (EFSA) draft opinion reviews literature on assessment of non-monotonic dose responses (NMDRs), finds lack of standards for statistical approaches; suggests stepwise approach for ambiguous ‘apparent’ NMDRs; approach applied in two case studies finds no NMDR for bisphenol A (BPA) but does for di(2-ethylhexyl)phthalate (DEHP); open for comments until February 4, 2021
On December 10, 2020 news provider Chemical Watch reported on a draft opinion on non-monotonic dose-response (NMDR) by the European Food Safety Authority (EFSA) that is open for consultation until February 4, 2021.
The draft opinion represents a follow-up to an external EFSA review (FPF reported) which concluded that “… criteria for evidence of NMDR, evaluation of data and importance for risk assessment had to be further evaluated.”
In their current review, the authors found, among others, that there is a lack of standards for statistical assessment approaches, which may lead to diverging conclusions for risk assessments.
Furthermore, the authors note that when assessing different NMDR studies, for some cases, biological effects clearly indicate an NMDR and therefore are well covered by current risk assessment principles. However, they also observed ambiguous cases with so-called ‘apparent’ NMDR where studies detected only effects at the molecular level, but these could possibly also lead to adverse effects in humans.
For this ‘apparent’ non-monotonicity, the authors suggest a step-wise evaluation approach. The draft opinion suggests, among other recommendations, that further investigation is needed if the effects are present in the whole organism and not supported by further experimental work. It is also important whether or not a mechanistic sequence (e.g. an adverse outcome pathway; AOP) could be partially or fully established. If one has been established, then-current methodologies for risk assessment may need to be reevaluated.
In the draft opinion, this proposed approach has been applied to two case studies on bisphenol A (BPA; CAS 80-05-7) and di(2-ethylhexyl)phthalate (DEHP; CAS 117-81-7). The authors concluded that no indications of NMDR were detected for BPA, while there were indications of a biologically plausible NMDR for DEHP.
EFSA is calling for feedback on their draft opinion. The call for comments will remain open until February 4, 2021.
Food Packaging Forum, 17 December 2020