In an article published on January 1, 2022, in the journal Food and Chemical Toxicology, Chia-Chi Wang from National Taiwan University, Taipei, Taiwan, and co-authors present a machine-learning based approach to evaluate food contact chemicals (FCCs) for carcinogenicity and prioritize the chemicals of highest concern.

The scientists compiled a list of 1623 unique chemicals with annotated chemical structures based on an indirect food additive list from the US FDA Center for Food Safety and Applied Nutrition (CFSAN). For each FCC, structural alerts (SAs), statistically based quantitative structure-activity relationships (QSAR, FPF reported), and in silico toxicogenomics (TGx) results were generated and integrated by a weight-of-evidence approach. Wang et al. identified 44 FCCs of high concern of carcinogenicity of which 33 are included in the International Agency for Research on Cancer’s (IARC’s) list as carcinogens or suspected carcinogens. For the remaining 11 chemicals, the carcinogenicity potential is unknown, making the authors suggest “further experimental investigation for the 11 FCCs […] to ensure food safety.” The scientists expect their developed weight-of-evidence approach could also be useful when evaluating carcinogenicity of chemicals beyond FCCs.

On December 21, 2021, the U.S. Department of Health and Human Services (HHS) released the 15th Report on Carcinogens prepared by the National Toxicology Program (NTP). Eight substances were newly listed, including the flame-retardant and polyethylene terephthalate (PET) catalyst antimony trioxide (CAS 1309-64-4, FPF reported and here), such that the report now includes 256 chemicals occurring in the environment that are considered to cause cancer.

In another article published on December 28, 2021, in the journal Chemosphere, Pietro Cozzini and colleagues from University of Parma, Italy, used physicochemical characteristics to identify FCCs for their potential interaction with nuclear receptors and, thus, with the human endocrine system. Using different European and North American sources, including Food Packaging Forum’s (FPF’s) Food Contact Chemicals database (FCCdb), Cozzini and co-authors compiled a database of 8091 substances that can come into contact with food including their three-dimensional structures. They classified the chemicals into 11 subclasses such as phthalates (361 chemicals), bisphenols (51), dioxins (75), furans (133), polychlorinated biphenyls (PCBs, 209), flavorings (2091) and those within the FCCdb (4268). The researchers applied a molecular docking approach and different scoring functions to identify the substances that can bind to 31 selected nuclear receptors and are therefore most probable to act as endocrine disruptors.

Cozzini et al. reported that “more than 50% of food contact chemicals are good interactors of liver X receptor β (LXRβ), pregnane X receptor (PXR), progesterone receptor (PR), farnesoid X receptor (FXR), retinoic acidrelated orphan receptor γ (RORγ), and peroxisome proliferator activated receptor α (PPARα).” Looking at the different chemical classes, almost all dioxins, furans, and PCBs were found to have a high binding affinity to more that 15 nuclear receptors while many flavorings, bisphenols, and FCCdb substances were rated as “medium interactors” with the receptors. The authors emphasized that these findings show “the potential capability of these molecules to cause a very broad endocrine effect on the human body.”

Computational methods can serve as a time- and cost-effective approach to screen the large number of existing chemicals to prioritize the chemicals of concern for further experimental evaluation (FPF reported and here).



Wang, C.-C. (2021). “A machine learning-driven approach for prioritizing food contact chemicals of carcinogenic concern based on complementary in silico methods.Food and Chemical Toxicology. DOI: 10.1016/j.fct.2021.112802

Cozzini, P. (2021). “Computational methods on food contact chemicals: Big data and in silico screening on nuclear receptors family.Chemosphere. DOI: 10.1016/j.chemosphere.2021.133422

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U.S. Department of Health and Human Services (December 21, 2021). “15th Report on Carcinogens.”