Suitability of the Ames test to characterise genotoxicity of food contact material migrates

Evaluation of the Suitability of Mammalian In Vitro Assays to Assess the Genotoxic Potential of Food Contact Materials

“…This means that a genotoxic response at this level cannot be detected for a broad range of DNA reactive substances, possibly leading to the underestimation of a genotoxic risk. In contrast, a literature survey on the suitability of the Ames assay for FCM screening [50] concluded that a level of 10 ppb was feasible for about 50% of genotoxic standard substances out of a given pool of 16 genotoxins, making this assay currently better suited for the characterization of directly DNA-damaging substances in FCM migrates. For other substances, such as aneugens or those interfering with DNA synthesis, the mammalian assays could detect 29% to 63% at concentrations below the threshold of 0.09 mg•L −1 , and therefore would be likely to detect them in FCM migrates as well.…”

“…In vitro assays can either be based on prokaryotic or eukaryotic cells and, depending on the mechanism of interest, different assays are suitable. Prokaryotic assays would exceed the scope of this review as the bacterial reverse mutation test (Ames) assay in the FCM context was recently evaluated [50]. For reasons of comparison, this assay will only be introduced for direct DNA reactive substances as it is recommended by the regulatory bodies for the testing of FCMs for mutagenic substances [11].…”

“…Finally, a solvent exchange takes place, where the migrated sample is transferred into a suitable solvent for bioassay application (e.g., dimethyl sulfoxide (DMSO)). Hence, the assumptions for the sample yield obtained are the following, which were also concluded by [50] • a theoretical concentration factor of 1000 [ With these assumptions, an overall factor of 10 is achieved for mammalian assays and 40 for the Ames test as it uses a dilution factor of 25 by applying 4% sample. To obtain the cLOBDs for the mammalian assays, the LECs found in the literature were divided by a factor of 10 to determine the theoretical detection in the FCM extract.…”

“…In order to perform the FCM exposure correlation, the TTC exclusion criteria thresholds should be considered for (1) structural genotoxicity alert (0.15 µg/person per day; by assuming a consumption of 1 kg or 1 L of the food per day, this corresponds to 0.00015 mg•L −1 for direct and indirect DNA-damage); and (2) aneugenic substances, which are threshold dependent as Cramer Class III [26] with 90 µg•person −1 per day, corresponding to 0.09 mg•L −1 . As a cLOBD of 0.00015 mg•L −1 is beyond reach with currently available bioassays, as concluded by [50], instead, a technical limit is used by applying European Regulation (EU) 10/2011. As already mentioned before, the EU proposes an analytical LOD of 10 ppb corresponding to 0.01 mg•L −1 [10].…”

Review of analytical approaches for the identification of non-intentionally added substances in paper and board food contact materials

“…The vendor specific software was used to find many suggestions for molecular formulas of a single m/z in the spectra, after which the isotope distribution was used to select the most matching one. They concluded that both isotope distribution and hits in the accurate mass database greatly increased the possibility of a correct percentage of the genotoxic substances that may be present at levels of 0.01 mg/kg (Rainer et al, 2018;Bolognesi et al, 2017).…”