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

Abstract

Food packaging is of high societal value because it conserves and protects food, makes food transportable and conveys information to consumers. It is also relevant for marketing, which is of economic significance. Other types of food contact articles, such as storage containers, processing equipment and filling lines, are also important for food production and food supply. Food contact articles are made up of one or multiple different food contact materials and consist of food contact chemicals. However, food contact chemicals transfer from all types of food contact materials and articles into food and, consequently, are taken up by humans. Here we highlight topics of concern based on scientific findings showing that food contact materials and articles are a relevant exposure pathway for known hazardous substances as well as for a plethora of toxicologically uncharacterized chemicals, both intentionally and non-intentionally added. We describe areas of certainty, like the fact that chemicals migrate from food contact articles into food, and uncertainty, for example unidentified chemicals migrating into food. Current safety assessment of food contact chemicals is ineffective at protecting human health. In addition, society is striving for waste reduction with a focus on food packaging. As a result, solutions are being developed toward reuse, recycling or alternative (non-plastic) materials. However, the critical aspect of chemical safety is often ignored. Developing solutions for improving the safety of food contact chemicals and for tackling the circular economy must include current scientific knowledge. This cannot be done in isolation but must include all relevant experts and stakeholders. Therefore, we provide an overview of areas of concern and related activities that will improve the safety of food contact articles and support a circular economy. Our aim is to initiate a broader discussion involving scientists with relevant expertise but not currently working on food contact materials, and decision makers and influencers addressing single-use food packaging due to environmental concerns. Ultimately, we aim to support science-based decision making in the interest of improving public health. Notably, reducing exposure to hazardous food contact chemicals contributes to the prevention of associated chronic diseases in the human population.

Full text

C O M M E N T A R Y Open Access
Impacts of food contact chemicals on
human health: a consensus statement
Jane Muncke
1*
, Anna-Maria Andersson
2
, Thomas Backhaus
3
, Justin M. Boucher
4
, Bethanie Carney Almroth
3
,
Arturo Castillo Castillo
5
, Jonathan Chevrier
6
, Barbara A. Demeneix
7
, Jorge A. Emmanuel
8
, Jean-Baptiste Fini
7
,
David Gee
9
, Birgit Geueke
1
, Ksenia Groh
1
, Jerrold J. Heindel
10
, Jane Houlihan
11
, Christopher D. Kassotis
12
,
Carol F. Kwiatkowski
13
, Lisa Y. Lefferts
14
, Maricel V. Maffini
15
, Olwenn V. Martin
16
, John Peterson Myers
17,18
,
Angel Nadal
19
, Cristina Nerin
20
, Katherine E. Pelch
13
, Seth Rojello Fernández
21
, Robert M. Sargis
22
, Ana M. Soto
23
,
Leonardo Trasande
24
, Laura N. Vandenberg
25
, Martin Wagner
26
, Changqing Wu
27
, R. Thomas Zoeller
28
and
Martin Scheringer
4,29
Abstract
Food packaging is of high societal value because it conserves and protects food, makes food transportable and
conveys information to consumers. It is also relevant for marketing, which is of economic significance. Other types
of food contact articles, such as storage containers, processing equipment and filling lines, are also important for
food production and food supply. Food contact articles are made up of one or multiple different food contact
materials and consist of food contact chemicals. However, food contact chemicals transfer from all types of food
contact materials and articles into food and, consequently, are taken up by humans. Here we highlight topics of
concern based on scientific findings showing that food contact materials and articles are a relevant exposure
pathway for known hazardous substances as well as for a plethora of toxicologically uncharacterized chemicals,
both intentionally and non-intentionally added. We describe areas of certainty, like the fact that chemicals migrate
from food contact articles into food, and uncertainty, for example unidentified chemicals migrating into food.
Current safety assessment of food contact chemicals is ineffective at protecting human health. In addition, society is
striving for waste reduction with a focus on food packaging. As a result, solutions are being developed toward
reuse, recycling or alternative (non-plastic) materials. However, the critical aspect of chemical safety is often ignored.
Developing solutions for improving the safety of food contact chemicals and for tackling the circular economy
must include current scientific knowledge. This cannot be done in isolation but must include all relevant experts
and stakeholders. Therefore, we provide an overview of areas of concern and related activities that will improve the
safety of food contact articles and support a circular economy. Our aim is to initiate a broader discussion involving
scientists with relevant expertise but not currently working on food contact materials, and decision makers and
influencers addressing single-use food packaging due to environmental concerns. Ultimately, we aim to support
science-based decision making in the interest of improving public health. Notably, reducing exposure to hazardous
food contact chemicals contributes to the prevention of associated chronic diseases in the human population.
Keywords: Food contact material, Migration, Food packaging, Non-intentionally added substance, Chronic disease,
Human health, Mixture toxicity, Endocrine disrupting chemical, Sustainable packaging, Circular economy
© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
* Correspondence: jane.muncke@fp-forum.org
1
Food Packaging Forum Foundation, Zurich, Switzerland
Full list of author information is available at the end of the article
Muncke et al. Environmental Health (2020) 19:25
https://doi.org/10.1186/s12940-020-0572-5

Background
We, as scientists working on developmental biology,
endocrinology, epidemiology, toxicology, and environ-
mental and public health, are concerned that public
health is currently insufficiently protected from harmful
exposures to food contact chemicals (FCCs). Import-
antly, exposures to harmful FCCs are avoidable. There-
fore, we consider it our responsibility to bring this issue
to the attention of fellow scientists with relevant expert-
ise, but currently not engaged in the area of FCMs, as
well as decision makers and influencers in government,
industry and civil society dealing with environmental
and health-related aspects of food packaging. We
propose that a broader, multi-stakeholder dialogue is ini-
tiated on this topic and that the issue of chemical safety
of food packaging becomes a central aspect in the dis-
cussions on sustainable packaging.
Food contact chemicals (FCCs) are the chemical constit-
uents of food contact materials and finished food contact
articles, including food packaging, food storage containers,
food processing equipment, and kitchen- and tableware
[1,2]. We define FCCs as all the chemical species present
in food contact articles, regardless of whether they are
intentionally added or present for other reasons.
It is clearly established by empirical data that FCCs
can migrate from food contact materials and articles into
food, indicating a high probability that a large majority
of the human population is exposed to some or many of
these chemicals [3]. Indeed, for some FCCs there is evi-
dence for human exposure from biomonitoring [4–11],
although some FCCs may have multiple uses and also
non-food contact exposure pathways.
When food contact material regulations were first de-
veloped, it had been generally assumed that low-level
chemical exposures, i.e. exposures below the toxicologic-
ally established no-effect level, pose negligible risks to
consumers, except for carcinogens [12,13]. However,
more recent scientific information demonstrates that
this assumption is not generally valid, with the available
evidence showing that exposure to low levels of endo-
crine disrupting chemicals can contribute to adverse
health effects [14–20]. In addition, chemical mixtures
can play a role in the development of adverse effects
[21–24], and human exposure to chemical mixtures is
the norm but currently not considered when assessing
health impacts of FCCs [1]. The timing of exposures
during fetal and child development is another critical as-
pect for understanding development of chronic disease
[25]. Currently, these new and important insights are
still insufficiently considered in the risk assessment of
chemicals in general, and of FCCs in particular [20]. We
have previously published an in-depth analysis of the sci-
entific shortcomings of the current chemical risk assess-
ment for food contact materials in Europe and the US
[1]. For example, in the European Union (EU) the regu-
lation EU 10/2011 includes a list of authorized sub-
stances for the manufacture of plastic materials and
articles in contact with food and, for some of the chemi-
cals, their permitted maximum concentration, either in
the plastic food contact article or in food (i.e. specific
migration limit) [26]. However, there are still many sub-
stances that are present in plastics and other materials
as non-intentionally added substances (NIAS). Even
though the EU regulations 10/2011 explicitly and EU
1935/2004 generally require a risk assessment of NIAS,
there are many difficulties: first, identification of NIAS is
very demanding [27] and, secondly, studying the effects
on human health is often not possible because for ex-
ample the chemicals are not available as pure substances
or testing would be too expensive [1]. What is more,
there is no regulatory requirement to assess toxic effects
of the chemical mixtures migrating from food contact
articles [1]. To summarize, we are concerned that
current chemical risk assessment for food contact che-
micals does not sufficiently protect public health.
Therefore, we would like to bring the following state-
ment to the attention of policy makers and stakeholders,
especially those currently working on the issue of pack-
aging waste but not focusing on the chemical safety of
food contact articles (Table 1). By mapping the challenges
(Table 2), we aim to initiate a broader debate that also in-
volves scientists with different expertise of relevance to
the issue. Importantly, chemical safety must be addressed
in two ways: e.g. (i) a discussion of how chemical safety is
ensured, based on the current scientific understanding
and e.g. (ii) a debate of the chemical safety of food pack-
aging in the circular economy, which aims at minimizing
waste, energy and resources use [28]. Therefore, we pro-
vide an overview of the most pressing challenges based on
current scientific understanding. Ultimately, the public is
to be protected from exposures to hazardous FCCs while
at the same time the aims of the circular economy need to
be achieved. To reach these goals, we think that there is a
need to better inform decision making on future food
packaging research and policy.
Part 1. Facts based on established scientific data
and findings
Chemicals migrate from all types of food contact materials
and articles
Chemicals can transfer from food contact materials and
articles into food. This phenomenon is known as migra-
tion and has been studied since the 1950s [29–33]. All
types of food contact materials may exhibit chemical mi-
gration, but the types of migrating chemicals and their
levels differ significantly. There are around 1200 peer-
reviewed scientific studies clearly demonstrating migra-
tion of multiple FCCs from food contact materials and
Muncke et al. Environmental Health (2020) 19:25 Page 2 of 12

articles (for example [29–32,34–66]). Migration is af-
fected by temperature, storage time, the chemistry of
both the food contact article and food, the thickness of
the food contact layer, and the packaging size (propor-
tionally higher migration from smaller packaging sizes
due to the increasing surface-area-to-volume ratio).
Several thousands of chemicals are intentionally used to
make food contact articles
Analysis of FCC lists issued by legislatures, industry, and
NGOs worldwide indicates that almost 12,000 distinct
chemicals may be used in the manufacture of food con-
tact materials and articles [67]. For example, European
Union (EU) and EU Member State regulations list a total
of 8030 substances for use in different types of food con-
tact articles [68]. In the United States (US), 10,787 sub-
stances are allowed as direct or indirect food additives,
and roughly half of these are FCCs [69]. Many additional
FCCs may be used in the US under the assumption of
being generally recognized as safe (GRAS), but they are
not notified to the US Food and Drug Administration
(FDA) and therefore no public record on their use is
available [70]. In general, information on the actual use
of a chemical in food contact materials (and its levels) is
difficult to obtain [71,72].
Toxicity and exposure information is available only for
few of the intentionally used chemicals
All migrating FCCs have inherent toxicity properties that
can cause different effects at different doses and are re-
lated to the timing of exposure, mode of action, and other
aspects. At the same time, levels of FCCs that humans are
exposed to reflect their use (or presence) in a food contact
article and are associated with its concentration in food.
To evaluate the risk of a given chemical to human health,
information on its inherent toxicity (i.e., its hazard) and
the actual levels of exposure is needed.
Many of the chemicals that are intentionally used in the
manufacture of food contact articles have not been tested
for hazard properties at all, or theavailabletoxicitydataare
limited [67]. Moreover, endocrine disruption, as a specific
hazard of concern, is not routinely assessed for chemicals
migrating from food contact articles, although some chem-
ical migrants are known endocrine disruptors [73–77].
Exposure data are commonly based on assumptions or es-
timates –for example derived from dietary assessments or
unpublished (proprietary) data of an intentionally used FCC’s
concentration in a food contact article [71,78,79]. Thus,
there is significant uncertainty associated with these data. In
short, decisions on the use of a chemical in food contact
materials are commonly made in data-poor situations.
Known hazardous chemicals are authorized for use in
food contact
Substances of very high concern (SVHC) are defined
under the EU regulation on the Registration, Evaluation,
Authorisation and Restriction of Chemicals (REACH) as
chemicals with unacceptable hazard properties (like
carcinogenicity, mutagenicity, toxicity for reproduction,
persistence and bioaccumulation, or endocrine disruption).
The human health effects of chemicals used in the manu-
facture of food contact materials are not covered by
Table 1 Overview of relevant stakeholders from the food contact and circular economy domains. Inter-governmental organizations
could convene these stakeholders from different backgrounds and initiate topical discussions on the issues detailed in Table 2
Stakeholder group Description
Intergovernmental organization Staff and expert working groups of the World Health Organization, Food and Agriculture Organization,
United Nations Environment Programme, etc.
Regulatory Global government officials and regulatory authority experts in the areas of food contact and
circular economy
Enforcement Enforcement officers
Risk assessment Experts in government agencies, third-party labs, industry and international working groups
Packaging and product design Experts designing and developing new “sustainable packaging”or business models for food
products in circular economies
Global food production Multinational food (processing) industry experts and decision makers
Local food production Farmers and primary producers, hospitality sector representatives
Retail Decision makers and experts on distribution of locally and globally produced foods
Food packaging manufacturing Chemical manufacturers (polymers, additives), converters, packaging manufacturers and their
supply chains
Food contact article manufacturing Chemical manufacturers, food processing equipment manufacturers, kitchen- and tableware
manufacturers, other food contact article producers and their supply chains
Waste management Government officials, industry experts and providers
Civil society Environmental and health NGOs, consumer advocacy groups, food movements
Science Academics, researchers in industry, governments, and NGOs, independent scientific consultants
Muncke et al. Environmental Health (2020) 19:25 Page 3 of 12

Table 2 Topics of concern (based on Table 2[1]) and examples of activities addressing them. This is not a complete and
comprehensive overview but rather a starting point for further discussions that essentially need to involve many stakeholders
(see Table 1)
Area Topic Description Example
A. DATA GAPS 1. Information on chemicals used in food contact
materials
Characterize types of chemicals used in
the manufacture of FCMs and FCAs, their
functions and levels
[67]
2. Information on non-intentionally added
substances
Compile existing information, develop strategies
and work plans to fill data gaps
[139,
140]
3. Information on migration of food contact
chemicals
Provide systematic overview of evidence for
migration from FCMs and FCAs
[130]
4. Empirical exposure data Measure migration into actual foods, assess intake
for different demographics (age groups, ethnic and
regional diversity)
B. METHODOLOGY
GAPS AND NEEDS
5. Comprehensive definition of adverse effects Expand the scope of toxicological testing requirements
to include non-cancer related endpoints such as
effects on the nervous, immune and endocrine systems,
and cardiovascular and metabolic effects
6. Approaches to addressing non-monotonic dose
response
Develop practical tools for use in chemical risk
assessment of FCCs
[119]
7. Approaches to addressing mixture toxicity Develop overall migrate testing for finished FCAs that can
be used in the regulatory context, including standardized
sample preparation
[141]
8. Develop a framework to address aggregate
exposures
Integrate exposure information from different legislative
areas when setting safe exposure thresholds
[142]
9. Develop a framework to address cumulative
exposures
Assess the safety of exposures to different chemicals
through the same or different exposure routes
10. Modernize tiered approach for screening and
prioritization
Include additional relevant endpoints for toxicity testing,
include testing of finished FCA
11. Compile information on human health
outcomes of exposure to FCCs
Assess systematically the available evidence for how
FCCs adversely impact human health; highlight data
gaps showing the need for appropriate longitudinal
studies that assess food contact chemicals
[130]
C. UPDATE
REGULATORY
PROCESSES
12. Overall regulatory framework for evaluation
beyond sector-specific regulations
Combine chemical hazard and possibly risk assessment
for different sectors in one legal framework
13. Requirements for data on use of FCCs Based on the principles of REACH, set legal requirement
to provide information about chemical use for market access
14. Need to reassess substances authorized for use
and/or generally recognized as safe
Policy instruments for removing authorized chemicals
e.g. indirect food additives, EU starting substances and
additives for plastic FCMs
15. Address bias in risk assessment Ensure that scientific judgement is placed in context of
personal values, acknowledge other sources of bias and
balance expert groups accordingly
16. Ensure transparency of decisions Communicate potential or real bias of decision makers
and experts making recommendations for decision makers
17. Improve enforcement Raise awareness to provide resources for enforcement
authorities to expand activities
[136]
18. Multi-stakeholder dialogues on practical
solutions
Address two key topics: 1.) Definition of safety for
FCCs: update according to current scientific knowledge;
2.)Food packaging in the circular economy: chemical
safety considerations
19. Integrate food packaging waste and safety
considerations
Policy must address both aspects simultaneously to avoid
conflicting goals
[138]
Muncke et al. Environmental Health (2020) 19:25 Page 4 of 12

REACH. However, the toxicity properties of SVHCs are
identical regardless of their use. Several SVHCs (i.e., known
hazardous chemicals) are authorized for use in food
contact in Europe and other countries [80]. For several
SVHCs, as well as other known hazardous substances,
there is evidence for migration from food contact articles
[73], for example migration of several ortho-phthalates
[81], per- and polyfluoroalkyl substances [63,82–84], and
perchlorate [85]. Notably, for substances classified as
SVHCs there is a societal consensus in Europe that their
use shall be phased out. Furthermore, in a circular
economy, where food packaging is made from recycled
materials, it is essential to ensure that no hazardous
chemicals are present in the materials because it will be very
difficult, if not impossible, to manage their risks effectively.
Food contact articles contain non-intentionally added
substances (NIAS) and most are unknown
In addition to intentionally used chemicals, food contact
articles also contain non-intentionally added substances
(NIAS) that may or may not have a technical function.
NIAS are impurities of starting substances or additives,
reaction by-products generated during manufacture along
the entire supply chain, or break-down products, e.g. from
additives [86]. More and more NIAS, including those with
evidence for migration, have been detected by modern
analytical methods, but many remain unidentified due to
prevailing limitations in structure elucidation [27,55,74,
87–95]. However, it is well known that for several types of
food contact materials, migration of NIAS is more
significant than migration of intentionally used substances
[3,96]. In conclusion, there are many unknown and/or
untested chemicals present in food contact articles.
Risk assessment of unknown chemicals is not possible
under the current regulatory approach
All migrating FCCs need to be assessed for their risk to
human health, and this requires information on both
hazard and exposure levels. But these data cannot be
generated for chemicals with unknown identity. There-
fore, the conventional risk assessment approach cannot
be applied to assessing the safety of these unidentified
FCCs [1]. Moreover, these NIAS contribute to the mix-
ture of migrating chemicals, which likewise cannot be
evaluated by conventional risk assessment strategies.
This implies that the human population is exposed to
unknown and/or untested chemicals migrating from
food contact articles, with unknown health implications.
Humans are exposed daily to mixtures of chemicals
migrating from food contact articles into food
A chemical mixture can cause adverse effects even if all
individual components of the mixture are present at
individually safe levels. Mixture toxicity is a scientifically
well-described phenomenon [23]. In general, FCCs
migrating from food contact articles are assessed for their
safety on a substance-by-substance basis. However, chem-
ical migration occurs in mixtures, therefore humans are
also exposed to chemical mixtures [1]. In addition to che-
micals migrating from food contact articles, humans are
exposed to chemicals from other sources, such as personal
care products, food contaminants or textiles.
Part 2. Areas of uncertainty
FCCs from food contact articles are a significant source of
chemical exposure
In the US, 40,655 chemicals are used in commerce today
[97] and in Europe 22,169 substances have been registered
under REACH [98]. Human exposure has been systema-
tically assessed for a fraction of these chemicals, including
for some FCCs [4,99–105]. However, for the majority of
FCCs it remains unknown if humans are exposed and at
what levels. At least 3221 exogenous chemicals have been
measured in human blood [106]. Various xenobiotics have
frequently been found in pregnant women, in the placenta
and cord blood, indicating that fetal exposure to mixtures
Table 2 Topics of concern (based on Table 2[1]) and examples of activities addressing them. This is not a complete and
comprehensive overview but rather a starting point for further discussions that essentially need to involve many stakeholders
(see Table 1)(Continued)
Area Topic Description Example
D. REPLACING
HAZARDOUS FCCs
20. Developing safer alternatives Based on revised definition of safety and updated toxicity
testing; develop screening assays for endocrine disruption
and other relevant endpoints
[134,
143]
21. Testing finished food contact articles Use combination of toxicity testing and chemical analysis
(“Effect-directed analysis”) to screen for hazardous but
unknown FCCs
[95]
22. Integrating human health with environmental
considerations: life cycle approach
Develop integrative assessment for environmental and
human health impacts, e.g. using life cycle analysis or
other method
[144]
23. Update sustainable packaging concept Define sustainable packaging to also include aspects
of human health protection that are based on current
scientific understanding
Muncke et al. Environmental Health (2020) 19:25 Page 5 of 12

of xenobiotics is the norm [107–111], and the health
impacts of this mixture exposure during early life remain
largely unknown, but effects on the human brain (i.e. de-
creased intelligence in children that were exposed pre-
natally to a mixture of EDCs) have been shown [21]).
Approximately 12,000 intentionally added substances
[67] and 30,000 to 100,000 non-intentionally added sub-
stances potentially migrate into food from various food
contact articles [112]. Appropriate chemical-analytical
methods are lacking for most of them [27,90,95,113,
114], which makes it currently impossible to discern the
contribution of these chemicals to the overall human
exposure to xenobiotics. However, food packaging is
estimated to be the most relevant source of human
exposure to plasticizers [71,115]. For comparison: it is
well known that the concentrations of FCCs in food-
stuffs exceed the concentrations of e.g. pesticide residues
in food by at least a factor of 100 [3]. Moreover, there
are fewer than 1000 pesticides in commercial use, and
chemical-analytical methods are available for all of them,
including their main metabolites.
Using generic thresholds for the safety assessment of
FCCs is inadequate
For FCCs without hazard data, generic concentration
thresholds are commonly used in their risk assessment.
For example, in Europe unauthorized chemicals may be
used in food contact plastics if their migration into food
is below the detection limit of 10 ppb (10 μg/kg food),
and if they are not genotoxic, mutagenic, toxic to
reproduction, or substances in nano-form [26]. In
practice this detection limit is often interpreted as a
safety threshold, for example in the revised Japanese
FCM legislation [116]. In the US, 0.5 ppb (0.5 μg/kg
food) is the Threshold of Regulation: for FCCs migrating
below this threshold, no hazard data need to be provided
if the chemical’s structure has no alerts for genotoxicity
[117]. But this approach is inadequate because it
assumes that “the dose makes the poison”. According to
the current scientific understanding of non-monotonic
dose responses, this is clearly not always the case
[18,19].Derivingasafethresholdmaynotbe
straightforward for chemicals with non-monotonic dose
responses, such as for endocrine disrupting chemicals
[14], because the results of standard high-dose toxicity
testing cannot simply be extrapolated to the low-dose
range. Chemicals with non-monotonic dose responses not
only have increasing effects with increasing dose but may
also have effects in the low-dose range [15,19]. A study
commissioned by the European Food Safety Authority
concluded that non-monotonic dose responses for several
food-related chemicals (such as FCCs) could neither be
confirmed nor rejected, and further investigation has been
recommended [118]. Guidance for addressing this
difficulty in chemical risk assessment has been published
[119]. Therefore, we find it concerning that this aspect is
not being taken up in general by (regulatory) chemical risk
assessment as it implies that humans are unnecessarily
exposed to hazardous chemicals.
Humans may be exposed to FCCs also from sources that
are non-food contact articles
Exposure levels to a given FCC need to be known to
determine if there is a risk, as a chemical’s risk is related
to both exposure and hazard. But in practice, obtaining
exposure data for FCCs is difficult, as the European
research project FACET has demonstrated [78], because
there is no systematic surveillance. As a result, exposure
levels of FCCs are mostly based on estimates, which are
associated with uncertainty and potentially underesti-
mate actual risk [79].
In addition, humans can be exposed to an FCC from
non-food contact sources (e.g. bisphenol A from food
packaging and thermal-paper receipts), too. This implies
that aggregate exposure is probable for at least some
FCCs [101,120]. Therefore, a threshold approach based
on exposure from only a single source may lead to an
underestimation of actual human risk since the actual
exposure is underestimated.
Combined exposure to mixtures of FCCs increases risk to
human health
Combination effects are not adequately addressed, even
though it is known that chemicals migrate from food
contact articles in mixtures. Novel approaches, such as
effect-directed analysis, where in vitro toxicity testing is
combined with chemical analysis, or semiquantitative
assessments, where chemicals with assumed highest ex-
posure levels are identified, can be useful for prioritization
of analytical chemistry work to identify chemicals of
concern in mixtures [27,74–76,86,92,121]. In vitro
screening for some aspects of endocrine disruption
can be used to assess such hazard properties in the overall
migrate, but the sample preparation, assay selection and
data interpretation aspects need to be further developed
[75,95,122–124].
The consequences of human exposure to FCCs need
careful investigation
The duration of time between FCC exposure and health im-
pact in humans can be very long, and suitable longitudinal
studies in the human population are mostly lacking [125].
Therefore, linking FCC exposure to adverse human health
outcomes is very difficult for many relevant substances.
Furthermore, in epidemiology, exposures to FCCs are
often not routinely assessed [126] and only studied for
very few individual FCCs. For some of the most contro-
versial chemicals like bisphenol A and phthalates,
Muncke et al. Environmental Health (2020) 19:25 Page 6 of 12

evidence continues to accumulate while thousands of other
FCCs that migrate into food lack hazard and/or exposure
information [127–129]. Therefore, a systematic assessment
oftheavailableevidenceisrequired[130]inorderto
identify and address pertinent knowledge gaps. This is of
urgency also for economic reasons, as the additional disease
costs related to exposures to endocrine disrupting
chemicals are significant, with annually US$ 340 billion in
the US and US$ 217 billion in the EU [131].
Part 3. Options for improvement
There is clear scientific evidence that chemicals migrate
from food contact articles, and it is likely that the major-
ity of the human population is affected by these expo-
sures. Some of the migrating chemicals are known
hazardous substances. Establishing causality between
chronic human exposure to chemicals from food pack-
aging (or other types of food contact articles) and adverse
health outcomes in humans is difficult. As a consequence,
there is a potentially large, but essentially unquantified,
burden of risk currently placed on citizens who are
unknowingly ingesting mixtures of unidentified and
untested chemicals that originate from food contact
articles with their daily food.
In addition, food packaging is of special interest in
discussions around the circular economy, and many solu-
tions are currently being proposed for reuse, recycling or
replacing plastic food packaging with alternative materials.
But those solutions mostly focus only on single aspects
such as reducing CO
2
emissions, energy use or plastic
littering, and often omit considerations of chemical
safety. This may lead to regrettable substitutions that
cause problems later.
Therefore, we urge policy makers, regulators, food and
food packaging manufacturers, civil society and scientists
from within the FCM world, and outside, to address
more attention to the issue of assessing the safety of
food contact chemicals, as it appears to be an important
opportunity for prevention of chronic diseases associated
with hazardous chemical exposures. We identify seven
areas of highest concern where we see an urgent need
for discussion and improvement:
Eliminating hazardous chemicals in food contact articles
Known hazardous chemicals should not be used in the
manufacture of food contact articles if their presence in
the finished article, by means of modern chemical ana-
lysis, cannot be excluded to a reasonable extent. Some
business operators have taken action on their food pack-
aging in the US [132], but other food contact articles,
such as processing equipment or filling lines, need to be
considered as well, and requirements should become
legally binding to encompass all food contact articles.
Authorized lists of chemicals for food contact uses
should be revised and known hazardous chemicals re-
moved, such as substances of very high concern (SVHC),
if their use is considered non-essential [133].
Developing safer alternatives
If the use of known hazardous chemicals is essential
and currently no suitable substitutes are available,
research into developing safer alternatives should be
apriority.Thedevelopmentofsaferalternatives
should be based on current scientific principles, such
as the Tiered Protocol for Endocrine Disruption
(TiPED) [134], as the safety definitions and related
criteria for establishing the risk of FCCs for human
health currently in place in the EU, US and else-
where are not aligned with the latest scientific
understanding [1]. Importantly, hazard identification
and characterization should be performed prior to
large-scale FCC use.
Modernizing risk assessment
Together with industry and civil society, regulatory
agencies should update what hazard and exposure data
are necessary for making safety determinations, based on
current scientific understanding [1]. Authorized sub-
stances for food contact that are currently in use should
be reassessed accordingly; this will also require a trans-
parent prioritization strategy that determines which
chemicals are reassessed first. Any values-based or
expert decisions affecting, for example, exposure esti-
mates, should be made transparent, e.g. when dealing with
data gaps or scientific uncertainty [135].
Including endocrine disruption
Chemical hazards related to endocrine disruption should
be assessed for all chemicals migrating from food con-
tact articles and for all substances that are intentionally
used in their manufacture. It is important to consider
the non-monotonic dose response phenomenon in
chemical risk assessment [135].
Addressing mixture toxicity
The mixture toxicity of the overall migrate, i.e. all
chemicals migrating from food contact articles, should
be determined for a relevant set of hazards such as
genotoxicity, mutagenicity, and endocrine disruption.
This means that finished food contact articles should
be tested in addition to single chemicals intentionally
used in their manufacture. Regulators and other
stakeholders should invest in research and develop-
ment for fast or high-throughput approaches to
screen the overall migrate. A general mixture toxicity
uncertainty factor should be introduced until better
approaches for dealing with mixtures have been
developed.
Muncke et al. Environmental Health (2020) 19:25 Page 7 of 12

Improving enforcement
Importantly, new regulations must be enforceable, and
sufficient resources for compliance control must be
made available to authorities [136]. Enforcement of rules
for known hazardous chemicals, such as carcinogens, is
necessary. Food contact articles should not be a source
of carcinogens migrating into food [128,129,137]. En-
forcement of rules on mixture toxicity must also be
practically feasible.
Finding practical solutions
A multi-stakeholder dialogue should be established to
identify solutions that are sustainable and focus on the
same goal, namely protecting humans and the environ-
ment while providing effective, efficient and affordable
food packaging in a circular economy. Such solutions
may be global in scope, but stakeholder needs will likely
vary between countries and cultural regions, and such
needs must be taken into account. Importantly, the
interface between food packaging and waste manage-
ment should be considered when new, practical solu-
tions are developed [138].
In Table 2, we provide an overview of different topics
that are relevant for the areas of concern.
Conclusions
We highlight that the human population is exposed
via food to chemicals migrating from food contact
articles such as food packaging. Many of these chemi-
cals are not sufficiently assessed for their impacts on
human health, while others are known hazardous sub-
stances. As a consequence, we see a need for revising
how the safety of migrating chemicals is assessed,
using current scientific understanding. At the same
time, different stakeholders are pushing for solutions
to reduce packaging waste and end plastic pollution,
but oftentimes not taking chemical safety into consid-
eration. Therefore, we encourage all stakeholders to
focus more on this issue and employ science-based
decision making in the interest of improving public
health. Reducing exposure to hazardous food contact
chemicals contributes to the prevention of associated
diseases in humans. And including chemical safety
considerations in the development of sustainable
packaging will lead to solutions that are beneficial to
both human and environmental health.
Abbreviations
FCC: Food contact chemical; NIAS: Non-intentionally added substance;
REACH: Registration, Evaluation, Authorisation and Restriction of Chemicals;
SVHC: Substance of Very High Concern; TiPED: Tiered protocol for endocrine
disruption
Authors’contributions
The content of the manuscript was drafted by JM and MS and revised by
MVM, JPM and RTZ. JM, MVM, JPM, MS and RTZ wrote the first draft. The first
draft and the revised manuscript was discussed during several conference
calls with all co-authors participating in some or all calls. All authors provided
written feedback and edits on the manuscript and agreed with its content.
Funding
This work has been funded by the Food Packaging Forum Foundation (FPF)
and the Plastics Solution Fund (PSF). PSF had no role in drafting the manuscript.
Availability of data and materials
Not applicable.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
JM, BG and KG are employees of the Food Packaging Forum (FPF), a
charitable foundation dedicated to science communication and research on
chemicals in all types of food contact materials and articles. FPF’s funding
relies on unconditional donations and project-related grants, including from
corporations in the glass packaging industry and foundations involved in the
prevention of plastic pollution. JB, MVM and OVM have project-based con-
tracts for working with FPF and receive remuneration for this role from FPF.
TB, JPM and MS are members of the FPF foundation board, and they are not
remunerated for this role. TB and MS are also board members of the Inter-
national Panel on Chemical Pollution (IPCP), an NGO that works on the issue
of chemical pollution in general. Both do not receive any personal benefits
from this work, financial or otherwise. AMA, DG, JHeindel, MVM, OVM, AN,
CN, AMS, LT, MW and RTZ are members of the FPF scientific advisory board
and they are not remunerated for this role but have received travel reim-
bursement from FPF for attending its meetings. BCA is a project partner in a
project coordinated by FPF and funded by MAVA Foundation and receives
funding for this work via FPF. JC, BAD, JBF, JHoulihan, CDK, KP, RMS and LV
are members of the scientific advisory group in a project coordinated by FPF
and funded by the Plastics Solution Fund, but they have not received fund-
ing for this role. LNV has received funding from the US NIH, Cornell Douglas
foundation and Paul G. Allen Foundation. She has been reimbursed for travel
expenses by numerous organizations including SweTox, Israel Environment
Fund, the Mexican Endocrine Society, Advancing Green Chemistry, ShiftCon,
US EPA, CropLife America, BeautyCounter, and many universities to speak
about endocrine disrupting chemicals. OVM is a European Parliament repre-
sentative on the European Chemical Agency Management Board and has
been appointed on the Joint Expert Group on Additives, Enzymes and other
Regulated Products of the UK Food Standard Agency. MVM works with NGOs
and the private sector on safety of FCCs. She has co-authored petitions
requesting U.S. FDA to revoke uses of FCC and food additives. BD is a co-
founder of the Watchfrog company but receives no financial compensation.
All other authors declare no competing interests.
Author details
1
Food Packaging Forum Foundation, Zurich, Switzerland.
2
Department of
Growth and Reproduction, International Center for Research and Research
Training in Endocrine Disruption of Male Reproduction and Child Health
(EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
3
Department of Biological and Environmental Sciences, University of
Gothenburg, Gothenburg, Sweden.
4
Institute of Biogeochemistry and
Pollutant Dynamics, ETH Zurich, Zurich, Switzerland.
5
Centre for
Environmental Policy, Imperial College London, London, UK.
6
Department of
Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine,
McGill University, Montreal, QC, Canada.
7
Department Adaptation du Vivant,
Unité mixte de recherche 7221, CNRS (French National Research Center) and
Muséum National d’Histoire Naturelle, Paris, France.
8
Institute of
Environmental & Marine Sciences, Silliman University, Dumaguete,
Philippines.
9
Institute of Environment, Health and Societies, Brunel University,
Uxbridge, UK.
10
Healthy Environment and Endocrine Disruptor Strategies,
Commonweal, Bolinas, CA, USA.
11
Healthy Babies Bright Futures,
Charlottesville, V.A., USA.
12
Nicholas School of the Environment, Duke
University, Durham, NC, USA.
13
The Endocrine Disruption Exchange, Eckert,
CO, USA.
14
Center for Science in the Public Interest, Washington, DC, USA.
Muncke et al. Environmental Health (2020) 19:25 Page 8 of 12

15
Independent Consultant, Frederick, MD, USA.
16
Institute for the
Environment, Health and Societies, Brunel University London, Uxbridge, UK.
17
Environmental Health Sciences, Charlottesville, Virginia, USA.
18
Department
of Chemistry, Carnegie, Mellon University, Pittsburgh, PA, USA.
19
IDiBE and
CIBERDEM, Universitas Miguel Hernandez, Elche, Spain.
20
University of
Zaragoza, I3A, Zaragoza, Spain.
21
Green Science Policy Institute, Berkeley, CA,
USA.
22
Division of Endocrinology, Diabetes, and Metabolism, Department of
Medicine, University of Illinois at Chicago, Chicago, IL, USA.
23
Department of
Immunology, Tufts University School of Medicine, Boston, MA, USA.
24
Department of Pediatrics, NYU Grossman School of Medicine, New York,
NY, USA.
25
Department of Environmental Health Sciences, School of Public
Health & Health Sciences, University of Massachusetts Amherst, Amherst, MA,
USA.
26
Department of Biology, Norwegian University of Science and
Technology (NTNU), Trondheim, Norway.
27
Department of Animal and Food
Sciences, University of Delaware, Newark, DE, USA.
28
Department of Biology,
University of Massachusetts Amherst, Amherst, MA, USA.
29
RECETOX, Masaryk
University, Brno, Czech Republic.
Received: 7 June 2019 Accepted: 4 February 2020
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