Assessment of the genotoxicity of acrylamide

Abstract

EFSA was requested to deliver a statement on a recent publication revisiting the evidence for genotoxicity of acrylamide (AA). The statement was prepared by a Working Group and was endorsed by the CONTAM Panel before its final approval. In interpreting the Terms of Reference, the statement considered the modes of action underlying the carcinogenicity of AA including genotoxic and non‐genotoxic effects. Relevant publications since the 2015 CONTAM Panel Opinion on AA in food were reviewed. Several new studies reported positive results on the clastogenic and mutagenic properties of AA and its active metabolite glycidamide (GA). DNA adducts of GA were induced by AA exposure in experimental animals and have also been observed in humans. In addition to the genotoxicity of AA, there is evidence for both secondary DNA oxidation via generation of reactive oxygen species and for non‐genotoxic effects which may contribute to carcinogenesis by AA. These studies extend the information assessed by the CONTAM Panel in its 2015 Opinion, and support its conclusions. That Opinion applied the margin of exposure (MOE) approach, as recommended in the EFSA Guidance for substances that are both genotoxic and carcinogenic, for risk characterisation of the neoplastic effects of AA. Based on the new data evaluated, the MOE approach is still considered appropriate, and an update of the 2015 Opinion is not required at the present time.

Impact of polyacrylamide supplementation on intake, nutrient digestion and growth of lambs

“…Therefore, in this experiment, the AA level in the diet for sheep with 50 kg BW was below 500 μg/kg, which was similar to that of french fries (ready-to-eat). European Food Safety Authority has declared the BMDL 10 (benchmark dose level 10) for AA in human as 170 μg/day/kg BW [ 43 , 44 ]. In this experiment, the amount of AA taken by sheep (with BW of 50 kg, 1.5 kg diet per day) through feed was below 15 μg/day/kg BW, therefore, it could be speculated that PAM level was safe for lamb and lambs meat could be safe for human consumption.…”

Quantitative in vitro to in vivo extrapolation of genotoxicity data provides protective estimates of in vivo dose

“…Glycidamide and acrylamide have AEDs on the same order of magnitude but very different exposure estimates (Table S4), the latter exposure estimate of acrylamide being more applicable to the existing risk assessment on acrylamide. In the EFSA's Scientific Opinion on acrylamide in food (EFSA Panel on Contaminants in the Food Chain (CONTAM), 2015; European Food Safety Authority (EFSA) et al, 2022), it was concluded that the MOEs for cancer‐related effects of acrylamide (425 for adults; 50 for toddlers) were in a range that was indicative of a concern for public health. Interestingly, the BER for acrylamide based on the median and minimum AEDs were 361 and 38 and these BERs were slightly lower than the MOE for adults and toddlers, respectively.…”

Multiobjective Optimization of a Frying Process Balancing Acrylamide Formation and Quality: Solution Analysis and Uncertainty Propagation

“…For a detailed review see [ 45 ] in which, among others, data on toxicology are included. EFSA in its latest report on the assessment of the genotoxicity of acrylamide [ 47 ], considered the possible modes of action of acrylamide carcinogenicity, including genotoxic and non-genotoxic effects. The paper concludes that there is substantial evidence for acrylamide genotoxicity mediated by metabolite formation, in addition to a possible contribution of non-genotoxic effects to acrylamide carcinogenicity.…”