New scientific opinion on genotoxic potential of acrylamide

The Senate Commission on Food Safety (SKLM) of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) has recently published, on the peer-reviewed journal Food and Chemical Toxicology, an opinion paper presenting arguments for an updated risk assessment of diet-related exposure to acrylamide (AA), a chemical that naturally forms in starchy food products during high-temperature cooking.    

The aim of this work was to complement earlier opinions and statements by specifically considering low dose AA exposure and to provide arguments in favor of the derivation of a health-based guidance value for AA based on a tolerable day intake (TDI).    

The authors state that, “as long as an appropriate exposure limit for AA is not exceeded, genotoxic effects resulting in carcinogenicity are unlikely to occur”. SKLM considers it scientifically justified to derive a TDI as a health-based guidance value.    

The manuscript presents SKLM’s reasons in support of a TDI value for AA, based on a critical review of scientific evidence relevant to low dose exposure to better reflecting realistic human dietary exposure scenarios.  In this article, AA doses ≥1 mg/kg bw/day (which are several orders of magnitude above the estimated human exposure; estimated as 0.4–1.9 μg/kg bw/day) are considered to be high doses from a toxicological point of view.    

The approach used by SKLM is driven by evidence arguing for the existence of nonlinear, thresholded dose-response relationships inherent in the toxicological characteristics of AA in the low dose range.    

In the opinion of the SKLM, new data have become available that justify the classification of AA as a chemical that does not significantly contribute to cancer risk in humans, provided an appropriate exposure limit is not exceeded. The SKLM substantiates the recommendation to reconsider the risk assessment of AA by the following science-based arguments (which are outlined in detail in the article):  
- Glycidamide (GA), the main metabolite of AA, is a weak mutagen/genotoxic agent.  
- At low dose level, AA only induces minimal DNA damage in vivo, which does not exceed the background range of similar human DNA damage.  
- At low dose level, metabolically formed GA is almost entirely scavenged by coupling with glutathione.  
- AA is formed endogenously in the body at concentrations in the lower range of human dietary exposure.    

SKLM concluded underlining the need to fill the gaps in the scientific knowledge, focusing on:  
- Advanced biomarker monitoring with reverse dosimetry, also considering endogenous background exposure in humans, its source(s) and variables of influence.  
- Physiologically based biokinetic (PBBK) modelling with a focus on defining thresholds of biomolecular key events with consequences for cancer induction in systems of high predictivity for humans.  
- Non-genotoxic effects.  
- Elucidation of the mechanisms and dose dependence underlying potential reproductive effects and other adverse outcomes.  
- Dose-related toxicogenomics in vitro and in vivo using experimental systems predictive for humans.      

 

Source:  

https://www.sciencedirect.com/science/article/pii/S0278691523000340?via%3Dihub