An article published on June 3, 2017 in the peer-reviewed journal Food and Chemical Toxicology reported on in silico assessment of potential genotoxicity of substances that may be used in coatings intended for food contact. Birgit Mertens and colleagues from the Department of Food, Medicines and Consumer Safety, Scientific Institute of Public Health, Brussels, Belgium, used several publicly available sources to compile a database of 3,046 unique substances that may be used in coatings. Among these, 1,976 substances were found to have either no toxicological evaluation at all, or an old toxicological evaluation (i.e., before 1991) only, and were therefore considered ‘non-evaluated.’ 836 of these substances were then evaluated for their genotoxic potential using two in silico prediction programs, ToxTree and Derek Nexus™, followed by a literature search to identify any previous evaluations performed in contexts other than food contact materials (FCMs). The remaining 1,140 of the non-evaluated substances could not be subjected to in silico analysis “due to the absence of the CAS number or an incompatibility with the . . . software.” Most of these substances were “polymers, mixtures, or poorly characterized compounds.”

Of the 90 substances that showed a structural alert for genotoxic carcinogenicity in the ToxTree program, 53 compounds also displayed an alert for one or more genotoxic endpoints in the Derek Nexus™. Regulatory evaluation in a context other than FCMs was found only for nine of these 53 compounds, and 25 substances (some overlapping) have also been registered under REACH. However, experimental data on genotoxicity was available only for 22 of these substances.

Out of these 22, 17 compounds were positive in one or more in vitro genotoxicity tests, and for eight substances positive results in vitro were clearly confirmed in a follow-up in vivo test. These eight substances, together with another two which have been classified as Category 2 Mutagens under the Classification, Labeling and Packaging (CLP) regulation, were designated as ‘high concern’ substances. These included aniline (CAS 62-53-3), p-aminophenol (CAS 123-30-8), 2,3-epoxypropanol (CAS 556-52-5), 2,3-epoxypropyl-o-tolyl-ether (CAS 2210-79-9), 2,3-epoxypropyl phenyl ether (CAS 122-60-1), [3-(2,3-epoxypropoxy)propyl]trimethoxysilane (CAS 2530-83-8), 2,3-epoxypropyl neodecanoate (CAS 26761-45-5), fluoroethylene (CAS 75-02-5), glyoxal (CAS 107-22-2), and 1,3,5-tris(oxiranylmethyl)-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (CAS 2451-62-9). The authors concluded that these substances should be urgently investigated regarding their actual use in food contact coatings, since to ensure safety, no migration into the food, or migration below a defined specific migration limit (SML), needs to be demonstrated.

Three compounds were considered to be of ‘medium concern’ because of equivocal in vivo testing results calling for more data. These included [[(2-ethylhexyl)oxy]methyl]oxirane (CAS 2461-15-6), isobutyraldehyde (CAS 78-84-2), and 7-oxabicyclo[4.1.0]hept-3-ylmethyl-7-oxabicyclo[4.1.0]heptane-3-carboxylate (CAS 2386-87-0).

For the remaining nine compounds, the available information suggested the absence of genotoxic effects, therefore these were designated as ‘low concern.’

It has to be reiterated that the presented analysis focused on less than a half of the ‘non-evaluated’ substances potentially used in coatings (836 out of 1,976), and for the 53 compounds identified as positive by both in silico programs, experimental data were available only for 22 compounds discussed above. For the remaining 31 substances, additional toxicological data should be generated to ensure their safe use. Furthermore, the authors emphasized that, due to inherent limitations of in silico prediction programs, “it should be kept in mind that compounds without SA [(structural alert)] for genotoxicity should not be automatically considered as non-genotoxic.” In addition, it should be noted that an in silico analysis can only evaluate the intentionally added substances, but not the non-intentionally added substances such as impurities, reaction products, or degradation products.


Mertens, B., et al. (2017). “Coatings in food contact materials : Potential source of genotoxic contaminants?Food and Chemical Toxicology (published June 3, 2017).