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. https://doi.org/10.1289/EHP644.

Department of Biological and Environmental Sciences University of Gothenburg Sweden

Department of Chemistry Carnegie Mellon University Pittsburg Pennsylvania USA

Department of Integrative Physiology and Pathobiology Tufts University School of Medicine Boston Massachusetts USA

Department of Pediatrics New York University School of Medicine New York New York USA

DTU Food Technical University of Denmark Copenhagen Denmark

Environmental Health Sciences Charlottesville Virginia USA

Food Packaging Forum Foundation Zurich Switzerland

Independent Consultant Germantown Maryland USA

Institute for Chemical and Bioengineering Swiss Federal Institute of Technology Zurich Switzerland

Institute for the Environment Brunel University London Uxbridge UK

Research Centre for Toxic Compounds in the Environment Masaryk University Brno Czech Republic

Comment In

Environ Health Perspect. 2018 Feb 20;126(2):024002. doi: 10.1289/EHP2602. PubMed

See more in PubMed

Alger HM, Maffini MV, Kulkarni NR, Bongard ED, Neltner T. 2013. Perspectives on How FDA Assesses Exposure to Food Additives When Evaluating Their Safety: Workshop Proceedings. Comprehensive Reviews in Food Science and Food Safety 12(1):90–119, 10.1111/j.1541-4337.2012.00216.x. DOI

Alonso-Magdalena P, Garcia-Arévalo M, Quesada I, Nadal Á. 2015. Bisphenol-A treatment during pregnancy in mice: a new window of susceptibility for the development of diabetes in mothers later in life. Endocrinology 156(5):1659–1670, PMID: 25830705, 10.1210/en.2014-1952. PubMed DOI

Balbus JM, Barouki R, Birnbaum LS, Etzel RA, Gluckman PD Sr, Grandjean P, et al. 2013. Early-life prevention of non-communicable diseases. Lancet 381(9860):3–4, PMID: 23290956, 10.1016/S0140-6736(12)61609-2. PubMed DOI PMC

Begley T, Castle L, Feigenbaum A, Franz R, Hinrichs K, Lickly T, et al. 2005. Evaluation of migration models that might be used in support of regulations for ood-contact plastics. Food Addit Contam 22(1):73–90, PMID: 15895614, 10.1080/02652030400028035. PubMed DOI

Bengtström L, Rosenmai AK, Trier X, Jensen LK, Granby K, Vinggaard AM, et al. 2016. Non-targeted screening for contaminants in paper and board food contact materials using effect directed analysis and accurate mass spectrometry. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 33(6):1080–1093, PMID: 27146477, 10.1080/19440049.2016.1184941. PubMed DOI

Bern H. 1992. The fragile fetus. In: Chemically-Induced Alterations in Sexual and Functional Development: The Wildlife/Human Connection (Colborn T, Clement C, eds). Princeton:Scientific Publishing Co, 9–15.

Bradley E, Coulier L. 2007. An investigation into the reaction and breakdown products from starting substances used to produce food contact plastics FD 07/01 London:Central Science Laboratory.

Bschir K. 2016. Risk, uncertainty and precaution in science: The Threshold of the Toxicological Concern approach in food toxicology. Sci Eng Ethics 23(2):1–20, PMID: 27192993, 10.1007/s11948-016-9773-2. PubMed DOI

Colborn T, vom Saal FS, Soto AM. 1993. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect 101(5):378–384, PMID: 8080506, 10.1289/ehp.93101378. PubMed DOI PMC

Cramer GM, Ford RA, Hall RL. 1978. Estimation of toxic hazard—a decision tree approach. Food Cosmet Toxicol 16(3):255–276, PMID: 357272, 10.1016/S0015-6264(76)80522-6. PubMed DOI

EFSA (European Food Safety Authority). 2012. Scientific Opinion on exploring options for providing advice about possible human health risks based on the concept of Threshold of Toxicological Concern (TTC). EFSA Journal 10(7):2750–2853, 10.2903/j.efsa.2012.2750. DOI

EFSA. 2016a. Recent developments in the risk assessment of chemicals in food and their potential impact on the safety assessment of substances used in food contact materials. EFSA Journal 14(1):4357–4365, 10.2903/j.efsa.2016.4357. DOI

EFSA. 2016b. Review of the Threshold of Toxicological Concern (TTC) approach and development of new TTC decision tree. EFSA Supporting Publication 13(3):EN-1006:50, 10.2903/sp.efsa.2016.EN-1006. DOI

EFSA. 2017. Administrative guidance for the preparation of applications for the safety assessment of substances to be used in plastic food contact materials. EFSA Supporting Publication 14(5):1224E, 10.2903/sp.efsa.2017.EN-1224. DOI

EC (European Commission). 2004. Regulation (EC) No 1935/2004 on materials and articles intended to come into contact with food. http://eur-lex.europa.eu/eli/reg/2004/1935/oj.

EC. 2011. Regulation (EU) No 10/2011 on plastic materials and articles intended to come into contact with food. http://eur-lex.europa.eu/legal-content/EN/TXT/?qid=1498596278669&uri=CELEX:32012R0528.

EC. 2017a. Food contact materials database. https://webgate.ec.europa.eu/foods_system/main/?event=display [accessed 8 June 2017].

EC. 2017b. RASFF: Food and feed safety alerts. http://ec.europa.eu/food/safety/rasff_en [accessed 8 June 2017].

Evans RM, Martin OV, Faust M, Kortenkamp A. 2016. Should the scope of human mixture risk assessment span legislative/regulatory silos for chemicals? Sci Total Environ 543(Pt A):757–764. PMID: 26573369, 10.1016/j.scitotenv.2015.10.162. PubMed DOI

Falk-Filipsson A, Hanberg A, Victorin K, Warholm M, Wallén M. 2007. Assessment factors—applications in health risk assessment of chemicals. Environ Res 104(1):108–127, PMID: 17166493, 10.1016/j.envres.2006.10.004. PubMed DOI

Food Additive Amendment of 1958. Food for human consumption. U.S. Code of Federal Regulations. 21 CFR 170.3.

FDA (U.S. Food and Drug Administration). 2002. Guidance for Industry: Preparation of Food Contact Notifications for Food Contact Substances: Toxicology Recommendations. http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/IngredientsAdditivesGRASPackaging/ucm081825.htm [accessed 8 June 2017].

FDA. 2015. Cumulative Estimated Daily Intakes (CEDI) database. http://www.fda.gov/Food/IngredientsPackagingLabeling/PackagingFCS/CEDI/default.htm [accessed 8 June 2017].

FDA. 2016. Compliance & enforcement. https://www.fda.gov/Food/ComplianceEnforcement/default.htm [accessed 8 June 2017].

FDA. 2017. List of available datasets. https://www.accessdata.fda.gov/scripts/fdcc/ [accessed 8 June 2017].

Geueke B, Wagner C, Muncke J. 2014. Food contact substances and chemicals of concern: a comparison of inventories. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 31(1):1438–1450, PMID: 24999917, 10.1080/19440049.2014.931600. PubMed DOI

Goodson WH 3rd, Lowe L, Carpenter DO, Gilbertson M, Manaf Ali A, Lopez de Cerain Salsamendi A, et al. 2015. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogensis 36(suppl 1):S254–S296, PMID: 26106142, 10.1093/carcin/bgv039. PubMed DOI PMC

Grob K. 2014. Work plans to get out of the deadlock for the safety assurance of migration from food contact materials? A proposal. Food Control 46:312–318, 10.1016/j.foodcont.2014.05.044. DOI

Grob K, Biedermann M, Scherbaum E, Roth M, Rieger K. 2006. Food contamination with organic materials in perspective: packaging materials as the largest and least controlled source? A view focusing on the European situation. Crit Rev Food Sci Nutr 46(7):529–535, PMID: 16954061, 10.1080/10408390500295490. PubMed DOI

Hoppe M, de Voogt P, Franz R. 2016. Identification and quantification of oligomers as potential migrants in plastics food contact materials with a focus in polycondensates – a review. Trends Food Sci Tech 50:118–130, 10.1016/j.tifs.2016.01.018. DOI

ILSI Europe 2015. Guidance on best practices on the risk assessment of non-intentionally added substances (NIAS) in food contact materials and articles. ILSI Europe Report Series. 1–70.

Jacobsen PR, Axelstad M, Boberg J, Isling LK, Christiansen S, Mandrup KR, et al. 2012. Persistent developmental toxicity in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides. Reprod Toxicol 34(2):237–250, PMID: 22677472, 10.1016/j.reprotox.2012.05.099. PubMed DOI

Kortenkamp A, Faust M, Scholze M, Backhaus T. 2007. Low-level exposure to multiple chemicals – reason for human health concern? Environ Health Perspect 115(suppl 1):106–114, PMID: 18174958, 10.1289/ehp.9358. PubMed DOI PMC

Koster S, Rennen M, Leeman W, Houben G, Muilwijk B, van Acker F, et al. 2014. A novel safety assessment strategy for non-intentionally added substances (NIAS) in carton food contact materials. Food Addit Contam Part A 31(3):422–443, PMID: 24237267, 10.1080/19440049.2013.866718. PubMed DOI

Kroes R, Renwick AG, Cheeseman M, Kleiner J, Mangelsdorf I, Piersma A, et al. 2004. Structure-based Thresholds of Toxicological Concern (TTC): guidance for application to substances present at low levels in the diet. Food Chem Toxicol 42(1):65–83, PMID: 14630131, 10.1016/j.fct.2003.08.006. PubMed DOI

Magnuson B, Munro I, Abbot P, Baldwin N, Lopez-Garcia R, Ly K, et al. 2013. Review of the regulation and safety assessment of food substances in various countries and jurisdictions. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 30(7):1147–1220, PMID: 23781843, 10.1080/19440049.2013.795293. PubMed DOI PMC

Markey CM, Coombs MA, Sonnenschein C, Soto AM. 2003. Mammalian development in a changing environment: exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs. Evol Dev 5(1):67–75, PMID: 12492412, 10.1046/j.1525-142X.2003.03011.x. PubMed DOI

McCombie G, Hötzer K, Daniel J, Biedermann M, Eicher A, Grob K. 2016. Compliance work for polyolefins in food contact: results of an official control campaign. Food Control 59:793–800, 10.1016/j.foodcont.2015.06.058. DOI

Muncke J. 2009. Exposure to endocrine disrupting compounds via the food chain: is packaging a relevant source? Sci Total Environ 407(16):4549–4559, PMID: 19482336, 10.1016/j.scitotenv.2009.05.006. PubMed DOI

Munro IC, Ford RA, Kennepohl E, Sprenger JG. 1996. Correlation of structural class with no-observed-effect levels: a proposal for establishing a threshold of concern. Food Chem Toxicol 34(9):829–867, PMID: 8972878, 10.1016/S0278-6915(96)00049-X. PubMed DOI

Nelson CP, Patton GW, Arvidson K, Lee H, Twaroski ML. 2011. Assessing the toxicity of polymeric food-contact substances. Food Chem Toxicol 49(9):1877–1897, PMID: 21723908, 10.1016/j.fct.2011.06.054. PubMed DOI

Neltner TG, Kulkarni NR, Alger HM, Maffini MV, Bongard ED, Fortin ND, et al. 2011. Navigating the U.S. Food Additive Regulatory Program. Compr Rev Food Sci F 10(6):342–368, 10.1111/j.1541-4337.2011.00166.x. DOI

Neltner TG, Alger HM, Leonard JE, Maffini MV. 2013a. Data gaps in toxicity testing of chemicals allowed in food in the United States. Reprod Toxicol 42:85–94, PMID: 23954440, 10.1016/j.reprotox.2013.07.023. PubMed DOI

Neltner TG, Alger HM, O’Reilly JT, Krimsky S, Bero LA, Maffini MV. 2013b. Conflicts of interest in approvals of additives to food determined to be generally recognized as safe: out of balance. JAMA Intern Med 173(22):2032–2036, PMID: 23925593, 10.1001/jamainternmed.2013.10559. PubMed DOI

Nerin C, Alfaro P, Aznar M, Domeño C. 2013. The challenge of identifying non-intentionally added substances from food packaging materials: a review. Anal Chim Acta 775:14–24, PMID: 23601971, 10.1016/j.aca.2013.02.028. PubMed DOI

Nordic Council of Ministers. 2005. Threshold of Toxicological Concern (TTC): Literature Review and Applicability. Copenhagen, Denmark:Nordic Council of Ministers.

Oldring P, O'Mahony C, Dixon J, Vints M, Mehegan J, Dequatre C, et al. 2014. Development of a new modelling tool (FACET) to assess exposure to chemical migrants from food packaging. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 31(3):444–465, PMID: 24215584, 10.1080/19440049.2013.862348. PubMed DOI

Pieke EN, Granby K, Trier X, Smedsgaard J. 2017. A framework to estimate concentrations of potentially unknown substances by semi-quantification in liquid chromatography electrospray ionization mass spectrometry. Anal Chim Acta 975:30–41, PMID: 28552304, 10.1016/j.aca.2017.03.054. PubMed DOI

Pinalli R, Croera C, Theobald A, Feigenbaum A. 2011. Threshold of toxicological concern approach for the risk assessment of substances used for the manufacture of plastic food contact materials. Trends Food Sci Tech 22(9):523–534, 10.1016/j.tifs.2011.07.001. DOI

Rancière F, Lyons JG, Loh VH, Botton J, Galloway T, Wang T, et al. 2015. Bisphenol A and the risk of cardiometabolic disorders: a systematic review with meta-analysis of the epidemiological evidence. Environ Health 14:46, PMID: 26026606, 10.1186/s12940-015-0036-5. PubMed DOI PMC

Seltenrich N. 2015. A hard nut to crack. Reducing chemical migration in food-contact materials. Environ Health Perspect 123(7):A174–A179, PMID: 26133041, 10.1289/ehp.123-A174. PubMed DOI PMC

Simoneau C. 2015. Annual report 2014 of the EURL-FCM on activities carried out for the implementation of Regulation (EC) No 882/2004. Joint Research Centre.

Simoneau C, Raffael B, Garbin S, Hoekstra E, Mieth A, Lopes JA, et al. 2016. Non-harmonised food contact materials in the EU: Regulatory and market situation. EUR 28357. https://ec.europa.eu/jrc/en/publication/eur-scientific-and-technical-research-reports/non-harmonised-food-contact-materials-eu-regulatory-and-market-situation-baseline-study [accessed 8 June 2017].

Shanklin AP, Cahill S. 2008. How FDA's Threshold of Regulation program works. http://www.foodsafetymagazine.com/magazine-archive1/december-2008january-2009/how-fdas-threshold-of-regulation-program-works/ [accessed 8 June 2017].

Trasande L, Zoeller RT, Hass U, Kortenkamp A, Grandjean P, Myers JP, et al. 2015. Estimating burden and disease costs of exposure to endocrine-disrupting chemicals in the European Union. J Clin Endocrinol Metab 100(4):1245–1255, PMID: 25742516, 10.1210/jc.2014-4324. PubMed DOI PMC

Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR Jr, Lee DH, et al. 2012. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev 33(3):378–455, PMID: 22419778, 10.1210/er.2011-1050. PubMed DOI PMC

WHO (World Health Organization). 2015. Noncommunicable diseases. Fact sheet. http://www.who.int/mediacentre/factsheets/fs355/en/ [accessed 8 June 2017].

Yang CZ, Yaniger SI, Jordan VC, Klein DJ, Bittner GD. 2011. Most plastic products release estrogenic chemicals: a potential health problem that can be solved. Environ Health Perspect 119(7):989–996, PMID: 21367689, 10.1289/ehp.1003220. PubMed DOI PMC

Evidence for widespread human exposure to food contact chemicals

Impacts of food contact chemicals on human health: a consensus statement