Scientific challenges in the risk assessment of food contact materials

Muncke J., Backhaus T., Geueke B., Maffini M.V., Martin O.V., Myers J.P., Soto A.M., Trasande L., Trier X., and Scheringer, M.
2017, Environmental Health Perspectives; Volume 125(9) (published September 11, 2017)

BACKGROUND: Food contact articles (FCAs) are manufactured from food contact materials (FCMs) that include plastics, paper, metal, glass, and printing inks. Chemicals can migrate from FCAs into food during storage, processing, and transportation. Food contact materials’ safety is evaluated using chemical risk assessment (RA). Several challenges to the RA of FCAs exist.
OBJECTIVES: We review regulatory requirements for RA of FCMs in the United States and Europe, identify gaps in RA, and highlight opportunities for improving the protection of public health. We intend to initiate a discussion in the wider scientific community to enhance the safety of food contact articles.
DISCUSSION: Based on our evaluation of the evidence, we conclude that current regulations are insufficient for addressing chemical exposures from FCAs. RA currently focuses on monomers and additives used in the manufacture of products, but it does not cover all substances formed in the production processes. Several factors hamper effective RA for many FCMs, including a lack of information on chemical identity, inadequate assessment of hazardous properties, and missing exposure data. Companies make decisions about the safety of some food contact chemicals (FCCs) without review by public authorities. Some chemical migration limits cannot be enforced because analytical standards are unavailable.
CONCLUSION: We think that exposures to hazardous substances migrating from FCAs require more attention. We recommend a) limiting the number and types of chemicals authorized for manufacture and b) developing novel approaches for assessing the safety of chemicals in FCAs, including unidentified chemicals that form during or after production.

Food contact materials and gut health: Implications for toxicity assessment and relevance of high molecular weight migrants

Groh K., Geueke B., and Muncke J.
2017, Food and Chemical Toxicology (published August 19, 2017)

Gut health is determined by an intact epithelial barrier and balanced gut microbiota, both involved in the regulation of immune responses in the gut. Disruption of this system contributes to the etiology of various non-communicable diseases, including intestinal, metabolic, and autoimmune disorders. Studies suggest that some direct food additives, but also some food contaminants, such as pesticide residues and substances migrating from food contact materials (FCMs), may adversely affect the gut barrier or gut microbiota. Here, we focus on gut-related effects of FCM-relevant substances (e.g. surfactants, N-ring containing substances, nanoparticles, and antimicrobials) and show that gut health is an underappreciated target in the toxicity assessment of FCMs. Understanding FCMs’ impact on gut health requires more attention to ensure safety and prevent gut-related chronic diseases. Our review further points to the existence of large population subgroups with an increased intestinal permeability; this may lead to higher uptake of compounds of not only low (<1000 Da) but also high (>1000 Da) molecular weight. We discuss the potential toxicological relevance of high molecular weight compounds in the gut and suggest that the scientific justification for the application of a molecular weight-based cut-off in risk assessment of FCMs should be reevaluated.

In vitro toxicity testing of food contact materials: State-of-the-art and future challenges

Groh K. and Muncke J.
2017, Comprehensive Reviews in Food Science and Food Safety (published July 14, 2017)

Currently, toxicological testing of food contact materials (FCMs) is focused on single substances and their genotoxicity. However, people are exposed to mixtures of chemicals migrating from food contact articles (FCAs) into food, and toxic effects other than genotoxic damage may also be relevant. Since FCMs can be made of more than 8 thousand substances, assessing them one-by-one is very resource-consuming. Moreover, finished FCAs usually contain non-intentionally added substances (NIAS). NIAS toxicity can only be tested if a substance’s chemical identity is known and if it is available as a pure chemical. Often, this is not the case. Nonetheless, regulations require safety assessments for all substances migrating from FCAs, including NIAS, hence new approaches to meet this legal obligation are needed. Testing the overall migrate or extract from an FCM/FCA is an option. Ideally, such an assessment would be performed by means of in vitro bioassays, as they are rapid and cost-effective. Here, we review the studies using in vitro bioassays to test toxicity of FCMs/FCAs. Three main categories of in vitro assays that have been applied include assays for cytotoxicity,
genotoxicity, and endocrine disruption potential. In addition, we reviewed studies with small multicellular animal-based bioassays. Our overview shows that in vitro testing of FCMs is in principle feasible. We discuss future research needs and FCM-specific challenges. Sample preparation procedures need to be optimized and standardized. Further, the array of in vitro tests should be expanded to include those of highest relevance for the most prevalent human diseases of concern.

Substances of very high concern in food contact materials: Migration and regulatory background

Geueke B. and Muncke J.
2017, Packaging Technology and Science (published online February 28, 2017)

Food contact materials (FCMs) are needed to produce, transport, process and store our food. Although essential for handling and protecting food from farm to fork, FCMs are often not inert, and chemical components may partition into food. In Europe, FCMs are regulated under the FCM Framework Regulation 1935/2004 which covers their effects on human health. Environmental effects of FCM substances are included in the scope of the European Chemicals Regulation [Regulation (EC) No 1907/2006 on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)] which aims at substituting Substances of Very High Concern (SVHCs) by safer alternatives. In this study, we focus on 10 FCM substances that are SVHCs and already included in the authorization list of REACH (Annex XIV): We show their possible application in the manufacture of FCMs and give evidence or highlight the absence thereof for migration into food or food simulants. An overview on migration of four phthalates (diisobutyl phthalate, dibutyl phthalate, benzyl butyl phthalate and bis(2-ethylhexyl) phthalate) and 4,4′-methylenedianiline from FCMs is provided, based on peer-reviewed studies and notifications from the Rapid Alert System for Food and Feed. Different approaches in evaluating and handling SVHCs under REACH and the European FCM legislation are discussed, and recommendations on how to increase the safety of FCMs are included. Combining better enforcement, an explicit ban of SVHCs without specific authorization for use in FCMs, and re-evaluations of previously authorized FCM substances could lead to safer FCMs. In conclusion, a harmonization between REACH and European FCM legislation is desirable for improving legal certainty for FCM users as well as in the interest of public health.

Food contact substances and chemicals of concern: A comparison of inventories

Geueke B., Wagner C.C. and Muncke J.
2014, Food Additives and Contaminants, Part A; Volume 31(8), pages 1438-1450.

Food contact materials (FCMs) are intended to be in contact with food during production, handling or storage. They are one possible source of food contamination, because chemicals may migrate from the material into the food. More than 6000 FCM substances appear on regulatory or non-regulatory lists. Some of these substances have been linked to chronic diseases, whilst many others lack (sufficient) toxicological evaluation. The aim of this study was the identification of known FCM substances that are also considered to be chemicals of concern (COCs). The investigation was based on the following three FCM lists: (1) the 2013 Pew Charitable Trusts database of direct and indirect food additives legally used in the United States (or Pew for short), (2) the current European Union-wide positive list for plastic FCMs (or Union for short), and (3) the 2011 non-plastics FCM substances database published by EFSA (or ESCO for short). These three lists of food contact substances (Pew, Union, ESCO lists) were compared with the Substitute It Now! (SIN) list 2.1, which includes chemicals fulfilling the criteria listed in article 57 of Regulation (EC) No. 1907/2006 (REACH), and the TEDX database on endocrine-disrupting chemicals. A total of 175 chemicals used in FCMs were identified as COCs. Fifty-four substances present on the SIN list 2.1 were also found on the Union and/or ESCO lists. Twenty-one of those 54 substances are candidates for Substances of Very High Concern (SVHC), and six of these 21 are listed on Annex XIV and intended for phase-out under REACH. In conclusion, COCs used in FCMs were identified and information about their applications, regulatory status and potential hazards was included.

Food packaging and migration of food contact materials: will epidemiologists rise to the neotoxic challenge?

Muncke J., Myers J.P., Scheringer M. and Porta M.
2014, Journal of Epidemiology & Community Health; Volume 68(7), pages 592-594.

Food contact materials (FCMs) are needed to produce, transport, process and store our food. Although essential for handling and protecting food from farm to fork, FCMs are often not inert, and chemical components may partition into food. In Europe, FCMs are regulated under the FCM Framework Regulation 1935/2004 which covers their effects on human health. Environmental effects of FCM substances are included in the scope of the European Chemicals Regulation [Regulation (EC) No 1907/2006 on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)] which aims at substituting Substances of Very High Concern (SVHCs) by safer alternatives. In this study, we focus on 10 FCM substances that are SVHCs and already included in the authorization list of REACH (Annex XIV): We show their possible application in the manufacture of FCMs and give evidence or highlight the absence thereof for migration into food or food simulants. An overview on migration of four phthalates (diisobutyl phthalate, dibutyl phthalate, benzyl butyl phthalate and bis(2-ethylhexyl) phthalate) and 4,4′-methylenedianiline from FCMs is provided, based on peer-reviewed studies and notifications from the Rapid Alert System for Food and Feed. Different approaches in evaluating and handling SVHCs under REACH and the European FCM legislation are discussed, and recommendations on how to increase the safety of FCMs are included. Combining better enforcement, an explicit ban of SVHCs without specific authorization for use in FCMs, and re-evaluations of previously authorized FCM substances could lead to safer FCMs. In conclusion, a harmonization between REACH and European FCM legislation is desirable for improving legal certainty for FCM users as well as in the interest of public health.