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.