+1(978)310-4246 credencewriters@gmail.com
  

Discussion 1

This is an ingredient packaging situation and one involving the shipping of ingredients such as cereal grain and flour in totes B2B.

This situation does not involve B2C.

Perchlorate is rapidly becoming the next chemical (after PFAS) on the radar esp for products consumed by Children.

Perchlorate  has been approved  as an antistatic agent or as a sealant since 2005 and in reusable packaging totes as well as in packaging for dry products

Up to 12,000 parts per million (ppm) of perchlorate can be added to plastic packaging for dry food with no free fat or oil

Perchlorate use in food contact materials may well explain the observed increase in perchlorate levels measured in foods sampled in 2003-2006 and 2008-2012

In 2014, several NGOs sent a petition to the FDA to revoke the permission to use perchlorate in food packaging on the grounds that there was an error in determining exposure levels

A 2022 ruling denied the petition

Importantly phthalates, BPA, and PFAs are not banned by the FDA.  However, the packaging industry reacted to consumers not wanting BPA, phthalates, and now PFAs within their food packaging, and these chemicals are used sparsely.  As a recent example, food brands are insisting upon PFAS and its derivatives are absent from paperboard packaging by the Fall of 2022.  However, paperboard and compostable that contain PFAS remain within our food packaging system, landfill, and compost.  This environmental disaster and exposure could have been avoided and we will explore how the VC could have been used to do this.

Let’s consider what the packaging industry and brands could/should have done in the early 2000s to proactively reduce the risk of something like Perchlorate from being used in reusable totes for dry B2B  ingredients (cereal grain, flour).

For each of the 2 interfaces, identify and explain a

specific value chain strategy

to proactively reduce the risk of something like Perchlorate from being used in the reusable totes for dry B2B ingredients (cereal grain, flour).  Then comment on the strategies of other students.

Interface 1: Reusable tote company – dry ingredient suppliers

Interface 2: Cereal ingredient supplier – Brand

1. Start 5 threads  (one for each of the interfaces. so 10 threads total) in 2-3 sentences that identify and explain a

specific value chain strategy/initiative

to proactively reduce the risk of something like Perchlorate being used in the reusable totes for dry B2B ingredients (cereal grain, flour).  The VC strategy needs to involve 2 entities and not just be an initiative that 1 company does.

Discussion #2

Discussion 2

For this week’s Discussion, each student will:

1. Start 10 threads that identify a cluster related to packaging .  Share why the cluster has value related to needed resilience as economies reshuffle, economic strife manifests itself in our interconnected world, and the climate changes. (~2-3 sentences each thread)

Let’s focus on the

economic

effectiveness

of the value chain. From an economic perspective, effective Value Chain development is challenged by trends which are:

the “reshuffling of world’s top economies.”

the need for effective energy management

increased urbanization of consumers

We have seen these trends increase with the effects of the pandemic.  One trend we saw advance before the pandemic was

agility

.  Agility has now manifested into more focus as the need for

resilience

. Let’s expand on the role of the packaging value chain and the use of clusters in providing resilience and agility as top economies reshuffle due to disasters, economic strife, and climate change.

Be sure to focus on the relevance to the value chain in your threads

below I will attach links that are the readings for the assignments. I will also attach a assignment 1 as well as another reading . please put all discussion 1 threads on one word document. all of discussion 2 threads on a separate document. and put assignment 1 on a separate word document as well.

New FDA commissioner has a full plate when it comes to chemistry of food safety

.

The Dangerous Food Additive That’s Not on the Label

Landing Page

COURSE: GSP 530: PACKAGING VALUE CHAIN
Packaging Value Chain Module 1 Assignment
Student Learning Objectives:
1. Understand the evolution of the packaging value chain
2. Define differences between the packaging supply chain and packaging value chain
3. Differentiate between value chain and supply chain solutions to address a current challenge
4. Explore the packaging value chain in the context of packaging suppliers.
5. Design value chain solutions for packaging suppliers that enhance their competitive advantage
through interfaces with 2 distinct entities within the value chain
Using the Perchlorate situation, we will explore what value chain activities in the 2000s would have
mitigated the current issue. And what the packaging value chain can do now to address the current
situation and build trust.
This is an ingredient packaging situation and one involving the shipping of ingredients such as cereal grain
and flour in totes B2B. This situation does not involve B2C.
Assignment specifics
Perchlorate is rapidly becoming the next chemical (after PFAS) on the radar especially for
products consumed by Children.
• Perchlorate has been approved as an antistatic agent or as a sealant since 2005 and is reusable
packaging totes as well as in packaging for dry products
• Up to 12,000 parts per million (ppm) of perchlorate can be added to plastic packaging for dry food
with no free fat or oil
• Perchlorate use in food contact materials may well explain the observed increase in perchlorate
levels measured in foods sampled in 2003-2006 and 2008-2012
• In 2014, several NGOs sent a petition to the FDA to revoke the permission to use perchlorate in
food packaging on the grounds that there was an error in determining exposure levels
• A 2022 ruling denied the petition
Importantly phthalates, BPA, and PFAs are not banned by the FDA. However, the packaging industry
reacted to consumers not wanting BPA, phthalates, and now PFAs within their food packaging, and these
chemicals are used sparsely. As a recent example, food brands are insisting upon PFAS, and its
derivatives are absent from paperboard packaging by the Fall of 2022. However, paperboard and
compostable that contain PFAS remain within our food packaging system, landfill, and compost. This
environmental disaster and exposure could have been avoided and we will explore how the VC could have
been used to do this.
Early 2000s
For each of the 2 interfaces, identify and explain a specific value chain strategy to proactively reduce the
risk of something like Perchlorate from being used in the reusable totes dry B2B ingredients (cereal grain,
flour. Then comment on the strategies of other students.
Interface 1: Reusable tote company – dry ingredient suppliers
COURSE: GSP 530: PACKAGING VALUE CHAIN
Interface 2: Plastic bag supplier – Brand
Now
For each of the 2 interfaces, identify and explain a specific value chain strategy to proactively reduce the
risk of something like Perchlorate from being used in the reusable totes or packaging dry B2B ingredients
(cereal grain, flour. Then comment on the strategies of other students.
Interface 1: Reusable tote company – dry ingredient suppliers
Interface 2: Plastic bag supplier – Brand
Part 3: Which of the strategies in the early 2000s would be most effective and why
Assignment Protocol
• Name, Due Date, and Topic on the first line.
• Limit of 2-pages single-spaced with 1-inch margins.
• Pages beyond 2 pages will not be graded.
• References (2) are to be listed on page 2.
• Due to the advanced level of the course, the content will be graded on how well-stated opinions are
reinforced with succinct examples, references, and documentation.
Please see comments (click boxes) within your graded assignment
Rubric for Grading
Part 1 – the early 2000s:
___/2 pts Interface 1: Reusable tote company – dry ingredient suppliers
___/2 pts Interface 2: Plastic bag supplier – Brand
Part 2 – Now:
___/2 pts Interface 1: Reusable tote company – dry ingredient suppliers
___/2 pts Interface 2: Plastic bag supplier – Brand
Part 3:
___/2 pts Which of the strategies in the early 2000s would be most effective and why
2 references required (-2pts if not present)
__/10pts Total
Environment International 150 (2021) 106225
Contents lists available at ScienceDirect
Environment International
journal homepage: www.elsevier.com/locate/envint
Review article
Overview of intentionally used food contact chemicals and their hazards
Ksenia J. Groh a, *, Birgit Geueke a, Olwenn Martin b, Maricel Maffini c, Jane Muncke a
a
Food Packaging Forum, Staffelstrasse 10, 8045 Zurich, Switzerland
Institute for the Environment, Health and Societies, Brunel University London, Quad North 17a, Kingston Lane, Uxbridge UB8 3PH, United Kingdom
c
Independent Consultant, Frederick, MD, USA
b
A R T I C L E I N F O
A B S T R A C T
Handling Editor: Olga-Ioanna Kalantzi
Food contact materials (FCMs) are used to make food contact articles (FCAs) that come into contact with food
and beverages during, e.g., processing, storing, packaging, or consumption. FCMs/FCAs can cause chemical
contamination of food when migration of their chemical constituents (known as food contact chemicals, FCCs)
occurs. Some FCCs are known to be hazardous. However, the total extent of exposure to FCCs, as well as their
health and environmental effects, remain unknown, because information on chemical structures, use patterns,
migration potential, and health effects of FCCs is often absent or scattered across multiple sources. Therefore, we
initiated a research project to systematically collect, analyze, and publicly share information on FCCs. As a first
step, we compiled a database of intentionally added food contact chemicals (FCCdb), presented here. The FCCdb
lists 12′ 285 substances that could possibly be used worldwide to make FCMs/FCAs, identified based on 67 FCC
lists from publicly available sources, such as regulatory lists and industry inventories. We further explored FCCdb
chemicals’ hazards using several authoritative sources of hazard information, including (i) classifications for
health and environmental hazards under the globally harmonized system for classification and labeling of
chemicals (GHS), (ii) the identification of chemicals of concern due to endocrine disruption or persistence related
hazards, and (iii) the inclusion on selected EU- or US-relevant regulatory lists of hazardous chemicals. This
analysis prioritized 608 hazardous FCCs for further assessment and substitution in FCMs/FCAs. Evaluation based
on non-authoritative, predictive hazard data (e.g., by in silico modeling or literature analysis) highlighted an
additional 1411 FCCdb substances that could thus present similar levels of concern, but have not been officially
classified so far. Lastly, for over a quarter of all FCCdb chemicals no hazard information could be found in the
sources consulted, revealing a significant data gap and research need.

Keywords:
Food contact material
Intentionally added substance (IAS)
Health hazard
Environmental hazard
Endocrine disruption
Persistence
Substitution
Abbreviations: Carc2, Carcinogenicity Category 2 hazard classification; CAS, Chemical Abstracts Service; CFR, Code of Federal Regulation; CFSAN, Center for Food
Safety and Applied Nutrition; C&L, Classification and Labeling; CMR, carcinogenic, mutagenic, toxic to reproduction; CPDat, Chemical and Products Database (a
database maintained by the US EPA); CompTox, computational toxicology; CoRAP, Community Rolling Action Plan; DSSTox, Distributed Structure-Searchable
Toxicity (a database maintained by the US EPA); DTXSID, Substance Identifier used in the DSSTox database; EC, European Commission; ECHA, European Chem­
icals Agency; EDC, endocrine disrupting chemical; EFSA, European Food Safety Authority; ENVH, environmental hazard; EPA, Environmental Protection Agency; EU,
European Union; FACET, Flavours, Additives, and food Contact materials Exposure Task; FCA, food contact article; FCC, food contact chemical; FCCdb, database of
intentionally added Food Contact Chemicals; FCM, food contact material; FCN, food contact substance notification; FCS, food contact substance; FDA, Food and Drug
Administration; GHS, Globally Harmonized System for classification and labeling of chemicals; HH, health hazard; IAS, intentionally added substance; IER, ionexchange resin; JRC, Joint Research Centre; Muta2, Mutagenicity Category 2 hazard classification; NIAS, non-intentionally added substance; NZIoC, New Zealand
Inventory of Chemicals; OECD, Organization for Economic Cooperation and Development; PBT, persistent, bioaccumulative, toxic; PMT, persistent, mobile, toxic;
PFAS, per- and polyfluoroalkyl substance; POP, persistent organic pollutant; REACH, Registration, Evaluation, Authorization and Restriction of Chemicals; Repr2,
Reproductive Toxicity Category 2 hazard classification; SIN, Substitute It Now; SVHC, substance of very high concern; TEDX, The Endocrine Disruption Exchange;
ToxVal, Toxicity Values (a database maintained by the US EPA); TSCA, Toxic Substances Control Act; UNEP, United Nation’s Environment Programme; vPvB, very
persistent, very accumulative; vPvM, very persistent, very mobile.
* Corresponding author at: Food Packaging Forum Foundation, Staffelstrasse 10, CH-8045 Zurich, Switzerland.
E-mail address: ksenia.groh@fp-forum.org (K.J. Groh).
https://doi.org/10.1016/j.envint.2020.106225
Received 3 July 2020; Received in revised form 12 October 2020; Accepted 16 October 2020
Available online 30 November 2020
0160-4120/© 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
K.J. Groh et al.
Environment International 150 (2021) 106225
1. Introduction
undisclosed. Therefore, the aim of this study was to compile a database
of intentionally used FCCs, based on globally-sourced regulatory posi­
tive lists and industry inventories that could be openly accessed and
easily interrogated. In addition, we recorded hazard information for the
identified FCCs from several reputable public sources, where available.
We discuss the collected information in the context of FCC use patterns
in different FCMs and reported hazardous properties.
Food contact materials (FCMs) can be defined as materials that come
into contact with food and beverages during food processing, packaging,
transport, storage, cooking, or serving. Different types of FCMs, for
example, plastics, paper, glass, metal, adhesives, or printing inks, can be
used, solely or in combination, to produce food contact articles (FCAs).
A typical FCA is food packaging, such as bottles or wraps. However, food
service items (e.g., cutlery) as well as food processing equipment (e.g.,
conveyor belts) or transport vessels also constitute a significant pro­
portion of FCAs overall.
FCMs and, consequently, FCAs, are made of and contain diverse
chemical constituents, which can be both intentionally used and nonintentionally present, here collectively referred to as food contact
chemicals (FCCs) (Muncke et al., 2017). Under certain conditions, FCCs
can be transferred into food, a phenomenon called migration (Arvani­
toyannis and Bosnea, 2004; Grob et al., 2006). In recent years, FCMs
have been subject to increasing attention and tightening regulations due
to widespread exposure and association with adverse health effects in
humans or in the environment (Hahladakis et al., 2018; Hermabessiere
et al., 2017; Muncke et al., 2020). The bulk of regulatory and research
activities currently focuses on a few substances or substance groups,
such as bisphenols (Tisler et al., 2016; Vandenberg et al., 2007),
phthalates (Zota et al., 2016), per- and polyfluoroalkyl substances
(PFAS) (Blum et al., 2015), certain metals (Turner, 2019), or mineral oil
hydrocarbons (Canavar et al., 2018; Grob, 2018). However, many more
FCCs that are known or suspected to be hazardous could also be
contributing to human exposure and health effects (Geueke and Muncke,
2018; Geueke et al., 2014; Grob et al., 2010; Liu and Mabury, 2019;
Mertens et al., 2016; Qian et al., 2018; Simoneau et al., 2016; Zim­
mermann et al., 2019). For example, 175 chemicals of concern have
been identified among a compiled list of approximately 6000 FCCs by
comparing it with several lists of known and suspected hazardous
chemicals (Geueke et al., 2014); a follow-up study reviewed migration
evidence for a subset of these hazardous FCCs (Geueke and Muncke,
2018). The use of any substance in FCMs requires proper risk assessment
and management (Nerin et al., 2018), but in practice this is not always
ensured. For example, over half of all chemical additives allowed to be
used in food in the US were found to lack appropriate toxicological data
required to determine their safety (Neltner et al., 2013).
FCCs can be divided into two groups, intentionally added substances
(IASs), i.e., substances that are deliberately used to manufacture FCMs
or FCAs, and non-intentionally added substances (NIASs), i.e., sub­
stances that have not been added on purpose and do not perform any
technical function, but are nonetheless present in the final FCMs or
FCAs. NIASs can include impurities, contaminants, reaction byproducts
and side products, and degradation products (Bradley and Coulier,
2007; Geueke, 2018; Nerin et al., 2013; Pieke et al., 2017). In 2016, the
European Commission’s Joint Research Centre (JRC) identified around
8030 IASs listed in the European member state regulations as being used
in so-called ‘non-harmonized FCMs,’ i.e., FCMs other than plastics, glass,
ceramics, or regenerated cellulose, for which a specific EU legislation
exists (Simoneau et al., 2016). For NIASs, estimates of 40′ 000 up to
100′ 000 substances have been proposed (Grob et al., 2006; MacCombie,
2018). To date, no publicly available studies have established a
comprehensive list of NIASs in FCMs, but there have been proposals to
develop approaches to predict NIASs using modeling based on IASs in­
formation (Hoppe et al., 2016). Thus, understanding the diversity of
IASs would be a required first step to a comprehensive characterization
of the chemical composition of FCMs and associated chemical exposures
throughout the whole life cycle of an FCA, from production to use and its
disposal stages.
A concise, publicly available resource listing all known FCCs that
could be intentionally used in FCMs or FCAs manufacture worldwide
does not exist, and the available information is typically scattered across
regulations and inventories for different FCM types, or remains
2. Materials and methods
2.1. Construction of the database of intentionally added food contact
chemicals (FCCdb)
The database of intentionally added food contact chemicals (FCCdb)
is a compilation of information on FCCs extracted from openly accessible
and searchable regulatory lists or industry inventories, sourced from the
countries considered the major economies in the world, where available.
The information sources were identified based on the references given in
the JRC’s baseline report on non-harmonized FCMs in the EU (Simoneau
et al., 2016). Notably, the JRC report referenced both European as well
as non-European sources, the latter consulted there for comparative
reasons. Several additional sources not referenced in the JRC report or
made available only after its publication were also included. A detailed
description of each information source included in the FCCdb is given in
the ‘Read Me’ tab accompanying the FCCdb worksheets in the Supple­
mentary File 1 or on Zenodo.
One prerequisite for inclusion of a substance into the FCCdb was its
identification by a Chemical Abstracts Service Registry Number (CAS
number) in the interrogated source, because the subsequent merging
with further sources was carried out based on the CAS identifier
matching. Thus, the substances that lacked an assigned CAS number in
the original source were not included in the FCCdb. An exception to this
rule was made for a large group of FCCs identified by a numerical code
in 977nnn-nn-n format that has been assigned by the US Food and Drug
Administration’s (US FDA) Center for Food Safety and Applied Nutrition
(CFSAN) to those substances that do not have a CAS number.
2.2. Exploration of FCCdb chemicals’ hazards and use
FCCdb chemicals’ hazards to human health and the environment
were explored based on hazard classifications aligned with the Globally
Harmonized System for classification and labeling of chemicals (GHS),
extracted from two sources: (1) classifications listed by the European
Chemicals Agency (ECHA) in its Classification and Labeling (C&L) in­
ventory
(ECHA-C&L,
see
https://echa.europa.eu/web/guest/
information-on-chemicals/cl-inventory-database) that includes both
the harmonized classifications (i.e., officially assigned by ECHA) and the
classification information received from manufacturers and importers
on notified and registered substances; and (2) classification results is­
sued by the Japanese Government (J-GHS, see https://www.nite.go.
jp/chem/english/ghs/ghs_index.html). Both GHS information sources
were interrogated on April 29, 2019, through the eChem portal
(http://www.echemportal.org) maintained by the Organization for
Economic Cooperation and Development (OECD). For FCCs that had
respective GHS classification(s), sum hazard scores for health hazards
(HH) and/or environmental hazards (ENVH) were then calculated. This
was done following a previously published methodology where smaller
or bigger numerical ‘hazard grade scores’ are assigned to each hazard
classification (i.e., a combination of a class and category of hazard)
depending on its severity (see Supplementary File 2). The ‘sum hazard
scores’ for each substance are then calculated as the sum of all ‘hazard
grade scores’ from the assigned classifications (Groh et al., 2019; Lithner
et al., 2011).
The hazard classes currently included in the GHS do not cover
endocrine disruption or persistency and bioaccumulation properties, but
these hazards are recognized by, e.g., the Registration, Evaluation,
2
K.J. Groh et al.
Environment International 150 (2021) 106225
Authorization and Restriction of Chemicals (REACH) legislation in the
EU (EU, 2006). We therefore deemed them relevant for the evaluation
here as well. For endocrine disruption, we consulted (i) the Endocrine
Disruptor Assessment List maintained by ECHA (http://echa.europa.
eu/ed-assessment/, downloaded on April 30, 2020), (ii) the list of sub­
stances placed due to their endocrine disrupting properties on the
Candidate List of substances of very high concern (SVHCs) for Autho­
rization under the REACH regulation in the EU, status May 2020
(http://echa.europa.eu/candidate-list-table), (iii) Endocrine Disruptor
Lists published by Denmark with involvement of four other European
member states (http://edlists.org, status May 2020), and (iv) lists of
recognized EDCs or potential EDCs compiled in the 2018 United Nations
Environment Programme’s (UNEP) report on EDCs (UNEP, 2018). For
persistence and bioaccumulation-related hazards, we consulted (i) the
PBT [persistent, bioaccumulative, toxic substance] Assessment List
maintained by ECHA (http://echa.europa.eu/pbt, downloaded on April
30, 2020), (ii) the list of substances placed due to their PBT or very
persistent, very bioaccumulative (vPvB) properties on the Candidate List
of SVHCs for Authorization under REACH, status May 2020, (iii) lists of
PBT substances identified by the US Environmental Protection Agency
(US EPA), and (iv) the list of substances covered by the Stockholm
Convention on Persistent Organic Pollutants (POPs) (http://www.pops.
int). Regulatory lists of hazardous substances that we consulted included
the REACH Candidate List of SVHCs for Authorization (http://echa.
europa.eu/candidate-list-table), the REACH Authorization List
(http://echa.europa.eu/authorisation-list), and the REACH Restriction
List (http://echa.europa.eu/substances-restricted-under-reach), as well
as the US California’s Proposition 65 list (http://oehha.ca.gov/pro
position-65-list/), all status May 2020. The hazard information ob­
tained from all of the above-described sources is considered highly
reliable as it has been agreed upon and accepted by multiple stake­
holders. Therefore, we collectively refer to such hazard information and
these sources themselves as “authoritative.” Only the above-listed
authoritative sources were considered when putting together the pri­
ority list of hazardous FCCs as described in Section 3.3.
Several other sources of hazard information can also be considered
authoritative but were not used for prioritization purposes. Instead,
these sources were consulted to extend the coverage of FCCdb chemicals
for which highly reliable hazard information could be available. These
sources included (i) the EU Community Rolling Action Plan (CoRAP) list
maintained by ECHA (http://echa.europa.eu/web/guest/informationon-chemicals/evaluation/community-rolling-action-plan/corap-table/,
downloaded May 1, 2020), (ii) the OpenFoodTox database compiled by
the European Food Safety Authority (EFSA) (Ceriani et al., 2018), which
provides chemical hazards data for all substances that have been eval­
uated by EFSA since its creation in 2002 (https://zenodo.org/record
/3693783#.Xq1dY2gzZaQ, version published on March 27, 2020),
and (iii) the US EPA’s Safer Chemical Ingredients List of the chemicals
that have been evaluated under the Safer Choice Program (https://www
.epa.gov/saferchoice/safer-ingredients#searchList, status April 2020).
Since the authoritative hazard information was available for only a
relatively small fraction of FCCdb chemicals, we also consulted several
other sources to obtain data for more FCCdb substances, which allowed
us to highlight additional substances of potential concern. We collec­
tively refer to these sources as providing “predicted” hazard classifica­
tions. These sources included i) advisory GHS-aligned chemical
classifications assigned by the Danish Environmental Protection Agency
based on in silico modeling (https://clp-vejlliste.mst.dk/default.aspx,
latest release searched in July 2019), ii) the Substitute It Now (SIN) list
maintained by the non-governmental organization International
Chemical
Secretariat
(ChemSec;
http://chemsec.org/business
-tool/sin-list/, November 2019 version), iii) The Endocrine Disruption
Exchange (TEDX) list of potential EDCs (https://endocrinedisruption.
org/interactive-tools/tedx-list-of-potential-endocrine-disruptors/,
September 2018 version), and iv) the analysis carried out by the German
Environment Ministry to identify persistent substances presenting
significant mobility-related hazards, i.e., persistent, mobile and toxic
(PMT), or very persistent, very mobile (vPvM) substances (Arp and Hale,
2019). Since the hazardousness of PMT substances has been recognized
only recently, this analysis represents one of the most comprehensive
studies on the topic existing to date. Lastly, we searched the Toxicity
Values (ToxVal) database compiled by the US EPA, which allowed us to
further explore the general availability of hazard data for FCCdb sub­
stances that could be obtained from governmental agencies such as US
EPA, JRC or OECD, as well as from scientific publications, since the
ToxVal database compiles toxicity information from many such sources
(Williams et al., 2017). For this analysis, the version 5 of the ToxVal
database (release of August 2018) was downloaded from http://com
ptox.epa.gov/dashboard/chemical_lists/TOXVAL_V5.
Use-related data in the FCCdb include a substance’s registration
status in REACH (https://echa.europa.eu/information-on-chemicals
/registered-substances/, accessed May 2019), regulatory status in the
EU as provided by the “chemical universe mapping” study performed by
ECHA
(https://echa.europa.eu/how-does-the-chemical-universemapping-work, accessed December 2019), and inclusion in the
ECHA’s database of plastics additives (https://echa.europa.
eu/de/mapping-exercise-plastic-additives-initiative, accessed May
2019), on the list of substances likely or possibly associated with plastic
packaging (Groh et al., 2019), on the US Toxic Substances Control Act
(TSCA) inventory (https://www.epa.gov/tsca-inventory/, accessed
June 2019), and on the New Zealand Inventory of Chemicals (NZIoC)
(http://www.cirs-reach.com/Inventory/New_Zealand_Inventory
_of_Chemicals-NZIoC.html, accessed June 2019). Additional details on
the consulted information sources can be found in the ‘Read Me’ tab
accompanying the FCCdb worksheets presented in the Supplementary
File 1 or on Zenodo.
Draw Venn Diagram tool at http://bioinformatics.psb.ugent.
be/webtools/Venn/ was used to examine overlaps between data subsets.
3. Results and discussion
3.1. Development of the food contact chemicals database (FCCdb)
Currently, the FCCdb integrates 67 different FCC lists extracted from
over 50 government and industry sources, and lists 12′ 285 substances
with unique CAS or CFSAN identifier. These information sources origi­
nate from five geographical areas: Europe, the US, the Mercosur region,
China, and Japan. As the consulted sources generally describe these
FCCs as intentionally added substances, it can be assumed that they are
being used (or have been in use until recently) in FCMs/FCAs manu­
facture in at least some parts of the world. The FCCdb version associated
with the submission of this manuscript can be found in the Supple­
mentary File 1. The FCCdb has also been added to the Zenodo repository
under https://doi.org/10.5281/zenodo.3240108. This link should be
consulted for the most recent version, as any future updates will be
published there as well.
3.1.1. Not all FCCs which could be in use are included in the FCCdb
For practical reasons and feasibility considerations, our compilation
method covered only the substances that had a CAS number (11′ 609
FCCdb substances) or a CAS-like identifier with a 977nnn-nn-n format as
assigned by the US FDA’s CFSAN (676 FCCdb substances). Most of the
676 substances with a CFSAN identifier appear only on the FDA lists,
with a few also included on the lists from Japan but not on any of the
European lists. Several hundred more FCCs that could be intentionally
used to make FCMs/FCAs are currently not included in the FCCdb
because these substances or substance groups do not have a CAS or
CFSAN identifier. For example, Annex I of the Regulation (EU) No. 10/
2011 (EU, 2011) lists 893 substances authorized for use in food contact
plastics in the EU, but 132 entries lack either of these two identifiers
(status 12th amendment, EU 2019/37). Many of these entries refer to a
group of substances each having a unique CAS number. These, however,
3
K.J. Groh et al.
Environment International 150 (2021) 106225
are not listed separately, but generic descriptions of chemical nature,
such as “perchloric acid, salts,” are provided instead. Similarly, Annex
10 of the Swiss ordinance on food contact materials (No 817.023.21)
contains over 150 entries lacking a CAS or a CFSAN identifier.
The absence of a common identifier complicates systematic assess­
ment and comparison with other lists and databases, e.g., resources that
compile information on hazardous properties. To improve transparency
and ease of assessment, it would be advisable that different sources
addressing intentionally used FCCs align their efforts to identify more
substances by a harmonized identifier type, such as the CAS number. For
generic entries, CAS numbers could be provided for the main repre­
sentatives of a particular group. The usefulness of the CFSAN-assigned
CAS-like identifier is much more limited, as it is largely confined to
US FDA sources and is rarely if ever included in databases outside this
agency. Similar concerns apply to other identifiers with limited coverage
that are commonly introduced internally, such as FCM reference
numbers used in the EU. One promising alternative identifier is the
DTXSID, which links to a specific chemical structure. This abbreviation
stands for the US EPA’s Distributed Structure-Searchable Toxicity
(DSSTox) database’s Substance Identifier. An ongoing US EPA initiative
seeks to map all chemicals in the Computational Toxicology (CompTox)
Chemistry Dashboard using DTXSID (Dionisio et al., 2018; Williams
et al., 2017), with the goal of promoting its future use to connect in­
formation from different sources. However, this new identifier has yet to
demonstrate its usefulness and reach universal acceptance.
telomer (CAS 220459-70-1). In contrast, three more substances that
are similarly prohibited or phased-out in the US were nonetheless
included in the FCCdb, because they are also mentioned by some Eu­
ropean and/or Mercosur sources, suggesting possible ongoing use:
ethylene thiourea (CAS 96-45-7), 4,4’-methylenebis(2-chloroaniline)
(CAS 101-14-4), and copolymer of 2-perfluoroalkylethyl acrylate, 2(dimethylamino)ethyl methacrylate, and oxidized 2-(dimethylamino)
ethyl methacrylate (CAS 479029-28-2).
The eight excluded substances are listed in the Supplementary File 1
in a separate worksheet called “FCCdb_excluded_substances.” An addi­
tional worksheet called “FCCdb_orphan_substances” lists 193 substances
which have been included on the final list in earlier FCCdb versions due
to being listed on one of the draft positive lists for certain FCMs, but are
not included there in the current version due to not being listed in the
respective final lists which have come into force by now. The final
FCCdb list used in all subsequent analyses presented below can be
viewed in the worksheet “FCCdb_FINAL_LIST” of the Supplementary File
1.
3.2. Global inventories of FCCs used in different FCM types
The information sources included in the FCCdb cover all the 17 FCM
types defined in the Regulation (EC) No 1935/2004 on materials and
articles intended to come into contact with food (EU, 2004), namely
plastics, coatings, rubber, silicones, ion-exchange resins (IERs), paper/
board, cellophane (regenerated cellulose), textiles, cork, wood, adhe­
sives, printing inks, wax, metals, glass, ceramics, and active & intelligent
materials. Colorants can be regarded as the 18th FCM type covered in
the FCCdb, as this group of substances is specifically covered by several
FCCdb sources, for example the French 2004 draft “Order on the col­
oring of plastic materials and articles, varnishes and coatings intended to
come into contact with foodstuffs, food products and drinks for human
and animal consumption” and the US FDA sources. The latter sources
also separately listed FCCs used in certain food processing operations, e.
g., as surface sanitizers, antimicrobials, rinse-aids, lubricants, or tracers.
To gain a better understanding of different FCC uses, we compiled
the so-called ‘global inventories’ of FCCs used in different types of FCMs
or other food contact applications. We compiled 16 global inventories in
total. Fifteen of them cover the 18 FCM types listed above (the FCCs used
in metal, glass, and ceramic FCMs are listed together in one global in­
ventory for “inorganic FCMs,” and cork and wood FCCs are also included
within one inventory named “cork/wood”). The 16th inventory for
“other uses” includes substances used in food contact applications other
than the production of FCAs, such as food processing operations. Each
FCC was assigned to none, one, or several inventories based on the in­
formation provided by the source(s) where this FCC is listed. For
example, all FCCs listed on the Union list for food contact plastics
(Annex I of the Regulation (EU) 10/2011) were assigned to the global
inventory for plastic FCMs. Many FCCs included in this global inventory
also appear in other FCM inventories, since they are also mentioned by
other FCCdb sources referring to other FCMs. The distribution of the 67
FCC lists from the FCCdb among the global inventories for each FCM
type can be viewed in the “Read Me” tab of the database file in the
Supplementary File 1.
The presented inventories should be viewed as indicative only,
because they often integrate information from both regulatory and nonregulatory, i.e., legally non-binding, sources, such as industry lists. We
call our inventories ‘global’ because they are based on FCC lists sourced
from different world regions, where available. For example, the global
inventory for plastic FCMs compiles FCCs from 13 lists, originating from
the US, Europe, China, Japan, and the Mercosur region. Given the everincreasing volumes of imports and cross-border trade, this approach
appears justified.
In total, 10′ 774 of 12′ 285 FCCdb substances could be assigned to at
least one of the 16 global FCM inventories, while for 1511 substances
information on their use could not be easily retrieved or was not
3.1.2. Some FCCdb substances could be outdated and not anymore in use
The FCCdb includes 4190 substances that are listed by just one of the
67 FCC lists. While this could be due to the specificity of a substance’s
use in just one FCM type, a particular application, or geographical
location, the rarity of a substance’s listing could also indicate that it is
outdated and not in use anymore, or has very limited use. For example,
among the 4023 chemicals extracted from the “food contact” group in
the Chemical and Products Database (CPDat) maintained by the US
Environmental Protection Agency (Dionisio et al., 2018), 1043 sub­
stances were unique to this list, i.e., not mentioned by any other FCC
sources included in the FCCdb. The developers of the largest source
included in the FCCdb, the Flavours, Additives, and food Contact ma­
terials Exposure Task (FACET) list for FCMs in Europe (Oldring et al.,
2014), have explicitly pointed out that the presence of a substance on
their list does not necessarily indicate its active FCM use at the moment.
Nonetheless, only 55 of the 5640 FACET-listed FCCs were unique to this
source. On the contrary, the US FDA Inventory of Indirect Additives
Used in Food Contact Substances contributed 3224 FCCdb substances of
which more than a quarter, 828 chemicals, were unique to this source.
Five more substances from this inventory were not included in the final
FCCdb list because, according to the US Code of Federal Regulation
(CFR) Title 21 189 Subpart D, they are “prohibited from indirect addi­
tion to human food through food-contact sources.” These substances are
lead solder (CFSAN ID 977182–76-5), tin coated lead foil (CFSAN ID
977182-75-4), poly(hydrogenated bisphenol A-co-triphenyl phosphite)
(CAS 27014-73-9), and 1,2-dihydro-2,2,4-trimethylquinoline (CAS 14747-7) and its polymer (CAS 26780–96-1). Two of these substances still
appeared in the “food contact” group on CPDat, but none of them is
listed by any other source outside the US, making it likely that their use
in FCMs has been completely discontinued. Similarly, three fluo­
rochemicals from the US FDA’s Inventory of Effective Food Contact
Substance (FCS) Notifications (FCNs) were not included in the final
FCCdb list because their FCM use has been “voluntarily ceased by the
manufacturer,” and they do not appear on any FCC lists outside the US.
These three substances are 2-perfluoroalkylethyl acrylate (CAS 6560570-1), copolymers of 2-perfluoroalkylethyl acrylate, 2-N,N-diethylami­
noethyl methacrylate, glycidyl methacrylate, acrylic acid, and meth­
acrylic acid (CAS 870465-08-0), and glycine, N,N-bis2-hydroxy-3-(2propenyloxy)propyl-, monosodium salt, reaction products with ammo­
nium hydroxide and pentafluoroiodoethane-tetrafluoroethylene
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Fig. 1. Proportion of FCCdb substances with defined types of food contact use. The pie chart shows the fractions of substances (in percentage of all 12′ 285 FCCdb
substances) which could not be assigned to any of the 16 global inventories (N = 0; 1511 substances) and of substances which could be assigned to at least one (N = 1;
6153 substances) or more (N = 2 up to N = 14; 4621 substances) inventories. The 16 global inventories cover food contact chemicals used in food contact plastics,
coatings, rubber, silicones, ion-exchange resins (IERs), paper/board, cellophane (regenerated cellulose), textiles, cork/wood, adhesives, colorants, printing inks, wax,
inorganics (including metals, glass, ceramics), active & intelligent materials, and other applications such as food processing operations.
which are intended to either actively interact with packaged food (e.g.,
by releasing antioxidants to prolong shelf life) or provide information
about the condition of packaged food (e.g., sensors of ripeness or
spoilage) (Dey and Neogi, 2019; Sohail et al., 2018; Vilela et al., 2018).
The two sources on this FCM type are a non-binding “Register of sub­
stances” last updated in 2011, which lists 39 substances intended to be
considered for a later inclusion on a positive list under the European
Regulation (EC) No 450/2009 on active and intelligent materials, and a
list of 61 substances extracted from the Recommendation XXXVI/3 for
“Absorber pads based on cellulosic fibers for food packaging,” issued by
the German Institute for Risk Assessment in 2009. Surprisingly, these
two lists overlapped by only one substance, cellulose (CAS 9004-34-6).
One more substance, not listed by these two sources, was identified in
the US FDA FCN inventory as being used as a component of an oxygen
sensor, thus resulting in the total number of 100 substances included on
the global inventory for active & intelligent FCMs. Due to a high un­
certainty and the current lack of comprehensive and binding positive
lists, this inventory is likely to be incomplete. However, even among
such a low total number of substances listed, 8 substances are unique to
this list only and have not been reported as FCCs intentionally used in
any other FCM type: 3,5,4’-trihydroxystilbene (resveratrol) (CAS 50136-0), monosodium glutamate (CAS 16177-21-2), (terephthalic acid,
dimethyl ester, polymer with 1,4-butanediol, cyclized, polymers with
glycidyl methacrylate, hydroxyl-terminated polybutadiene, methyl
methacrylate and styrene) copolymer (CAS 1223402-34-3), calcium
chloride hexahydrate (CAS 7774-34-7), chabazite (calcium aluminum
silicate, CAS 12251-32-0), clinoptilolite (CAS 12173-10-3), palladium
(CAS 7440-05-3), and platinum 5,10,15,20-tetrakis(pentafluorophenyl)
porphyrin (CAS 109781-47-7). While some of these substances are
better known and some are even directly added to food or drugs (e.g.,
resveratrol, sodium monoglutamate), the safe use of others may need
additional assessment. For example, palladium is suspected to be a
potent allergen (Faurschou et al., 2011; Wiseman and Zereini, 2009),
frequent use of antimicrobials could be of concern in a context of global
spread of antimicrobial resistance (Gillings, 2017; Hegstad et al., 2010),
and the safety of nanomaterials used in FCMs is still debated (Groh et al.,
2017; Jokar et al., 2017; Morais et al., 2019). Given the high pace of
development and marketing of FCAs that employ active & intelligent
FCMs, better oversight and more data on the associated FCCs and
resulting exposures are needed.
available. Roughly half (6153) of all FCCdb substances are assigned to
only one FCM inventory, while the remaining 4621 substances appear
on two and up to 14 global FCM inventories (Fig. 1). The six most
frequently mentioned substances are formaldehyde (CAS 50-00-0,
assigned to 14 inventories), isopropanol (CAS 67-63-0, 13 in­
ventories), and acrylic acid (CAS 79-10-7) along with sodium poly­
acrylate (CAS 9003-04-7), vinyl chloride (CAS 75-01-4), and styrene
(CAS 100-42-5), each assigned to 12 inventories.
The total numbers and overlaps between the FCCs assigned to the 16
global inventories are shown in Table 1. For example, the global in­
ventory for plastic FCMs includes 4742 substances in total, of which
1437 are unique to food contact plastics, as they do not appear on global
inventories for any other FCM type. Global inventories for food contact
plastics and coatings share 2008 substances, which corresponds to 42%
of plastics FCCs and 70% of coatings FCCs (Table 1). Compared to the
numbers of FCCs that the JRC’s baseline study found to be known to or
regulated by different EU member states (Simoneau et al., 2016), our
global inventories contain higher substance numbers for all FCM types,
underscoring the global nature of the included sources. The highest
numbers of FCCs are found in the global inventories for printing inks,
plastics, paper/board, and coatings, with 5625, 4742, 2950, and 2886
included substances, respectively. These FCM types also harbor partic­
ularly high numbers of unique FCCs, especially the printing inks with
2926 unique substances (52% of all FCCs assigned to this FCM type). The
large number of diverse substances used in printing inks has been
highlighted previously in the JRC’s report on FCMs (Simoneau et al.,
2016). Contrary to our study, the JRC report did not discuss colorants as
a separate FCM type. In our comparison, however, only 183 out of 316
substances on the global inventory for food contact colorants (58%)
were also assigned to the printing inks inventory, thus justifying the
identification of the former as a separate FCM type.
The smallest numbers of FCCs are included in the global inventories
for active & intelligent materials (100), inorganics (101), and wax (142),
with correspondingly low numbers of unique substances (Table 1).
However, the total number of substances on a given inventory may
reflect not only the actual diversity of chemicals used in a given FCM
type, but also the abundance or scarcity of available information sources
for this material. For example, while the global inventory for plastic
FCMs currently compiles information from 13 different lists, only two
dedicated sources could be identified for active & intelligent materials.
This FCM type is used to make FCAs with rapidly growing market share
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Environment International 150 (2021) 106225
Table 1
Total numbers and overlaps between substances assigned to 16 global inventories for different food contact materials and other food contact applications.
overlap with global inventories
for other FCM types
global inventory,
FCM type: plastics
plastics
4742
coatings
coatings
2008
2886
rubber
rubber
726
582
1043
silicones
silicones
507
471
254
784
IERs
IERs
415
378
203
298
555
P&B
paper/board
1334
1270
488
350
281
2950
cellophane
cellophane
301
262
156
111
79
257
365
textiles
textiles
77
77
37
14
16
169
25
207
cork/wood
124
168
79
53
43
184
32
12
219
adhesives
adhesives
1275
981
461
254
205
1032
216
51
163
1788
cork/wood
colorants
colorants
224
129
44
31
14
88
15
4
8
40
316
inks
printing inks
1955
1590
549
555
392
1309
17
72
109
744
183
5625 wax
wax
57
114
28
10
9
123
10
4
98
118
2
38
142 inorganics*
inorganics
57
36
28
17
4
38
11
5
4
15
12
38
0
101
A&I
75
70
51
37
41
83
26
7
16
49
8
74
4
6
100
other**
130
75
39
25
42
84
27
7
10
52
10
101
4
1
9
208
unique substances
1437
331
172
144
84
745
17
20
6
154
38
2926
3
26
8
42
total
325
219
175
75
76
256
22
19
33
147
10
377
8
28
18
19
unique
36
6
12
2
5
39
0
0
2
1
0
83
0
5
0
0
prioritized
hazardous
substances
A&I
other
*Covers metals, glass, ceramics
**Covers other food contact uses, e.g., during food processing or preparation.
Abbreviations: FCM, food contact material; IERs, ion-exchange resins; P & B, paper and board; A & I, active and intelligent materials.
3.3. Prioritization of FCCdb chemicals recognized as hazardous by
authoritative sources
of CAS-identified FCCdb substances) and the list maintained by the
Japanese government (J-GHS; classifications available for 1177 (10.1%)
of CAS-identified FCCdb substances). Together, these two sources pro­
vided at least one HH or ENVH classification for only 1466 (12.6%) of
CAS-identified FCCdb substances (Table 2). Hazard ranking was per­
formed following previously published methodology (Groh et al., 2019;
Lithner et al., 2011), where hazard classifications available for each
substance are assigned pre-defined numerical scores reflecting their
severity (see Supplementary File 2), and the sum hazard scores for each
substance are then calculated by adding up the hazard scores for indi­
vidual HH and ENVH classifications. In this framework, substances that
have at least one carcinogenic, mutagenic, or toxic to reproduction
(CMR) classification with the highest hazard category of 1 would receive
the sum hazard score for HH that equals or exceeds 10′ 000. Therefore,
all substances receiving the sum hazard score for HH ≥ 10′ 000 were
considered priority hazardous substances. For ENVH, we prioritized
substances with the sum hazard score of 1000 and above, because this
range covers substances that have the highest hazard category of 1 for
the chronic aquatic toxicity, with or without acute toxicity classification.
Based on classifications from the ECHA-C&L source, 187 and 146 sub­
stances were prioritized for HH and ENVH, respectively, while analysis
based on J-GHS classifications prioritized 146 and 182 substances for
HH and ENVH, respectively. Somewhat unexpectedly, the lists of HH or
ENVH priority substances thus derived from ECHA-C&L and J-GHS
sources showed only a moderate overlap, both in terms of the identity of
classified chemicals and in terms of classifications assigned to over­
lapping chemicals. Specifically, only 70 substances received the HH sum
hazard scores of ≥ 10′ 000 from both ECHA-C&L and J-GHS sources, and
only 62 substances had the ENVH sum hazard score ≥ 1000 from both
sources. Given the apparent differences in the scope of substances
covered by these two sources, we decided to consider hazard
Sound chemicals management should encourage continuous efforts
to substitute hazardous chemicals used in processes and products with
safer alternatives in order to enable the transition to a toxic-free envi­
ronment (Goldenman et al., 2017) and to facilitate the emergence of
clean circular economy based on non-toxic material cycles (Bodar et al.,
2018; Geueke et al., 2018; Turner, 2018). To support these efforts in the
area of FCMs, we sought to assemble a comprehensive list of FCCs that
should be most urgently considered for substitution due to their intrinsic
hazardous properties making them harmful to human health and/or the
environment. A multitude of resources providing different types of
hazard information can be found in the public domain, which, however,
have widely variable recognition and reliability status, and also differ in
their coverage of chemical space and hazard types. Therefore, we first
focused on selected authoritative sources of hazard information, which
we searched by CAS identifiers available for 11′ 609 FCCdb substances
(Table 2). The 676 FCCdb substances that have no CAS number but only
a CFSAN-assigned identifier had to be omitted from this analysis,
because none of the sources consulted offered a CFSAN identifier-based
search. Thus, the numbers and percentages given in Table 2 and dis­
cussed below should be interpreted in relation to the 11′ 609 FCCdb
substances with a unique CAS number.
3.3.1. Prioritization based on GHS-aligned classifications for health and
environmental hazards
We explored the FCCdb chemicals’ hazards to health (HH) or the
environment (ENVH) based on respective GHS-aligned classifications
extracted from two authoritative sources: the ECHA’s Classification and
Labeling inventory (ECHA-C&L classifications available for 900 (7.8%)
6
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Environment International 150 (2021) 106225
Table 2
Availability of hazard information for CAS-identified FCCdb chemicals in the sources consulted.
*Rows in bold show prioritization criteria and numbers of substances prioritized according to these criteria based on selected authoritative sources (see sections
3.3.1–3.3.4). Blue, orange and green backgrounds correspond to Venn diagram colors used in Fig. 2.
**All substances on this list are also included in the REACH SVHC List.
7
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Fig. 2. Total numbers and overlaps between 608
FCCdb substances prioritized for substitution
based on selected authoritative sources of hazard
information. (A) Prioritization based on globally
harmonized system (GHS)-aligned classifications
for health hazards (HH, N = 263) and environ­
mental hazards (ENVH, N = 266), total N = 482.
(B) Prioritization based on the authoritative
identification as substance of concern due to
endocrine disrupting or persistence-related haz­
ards (total N = 54, includes endocrine disrupting
chemicals (EDCs) recognized in the EU under the
REACH or Biocides legislation (EDC, N = 22) and
substances recognized in the EU or US as persis­
tent, bioaccumulative and toxic (PBT), or very
persistent, very bioaccumulative (vPvB), or as
persistent organic pollutants (POPs) under
Stockholm convention (PBT + vPvB + POP, N =
32)) and overlap with substances prioritized
based on GHS classifications (HH + ENVH, N =
482). (C) Prioritization due to inclusion on the
EU- or US-relevant regulatory lists of hazardous
substances (total N = 378): EU Registration,
evaluation, authorization and restriction of
chemicals (REACH) legislation’s list of substances
of very high concern (SVHC), also called Candi­
date list of SVHCs for authorization (REACH
SVHC, N = 123), REACH Restriction list, also
called Annex XVII (REACH Restriction; N = 255),
and US California Proposition 65 list (N = 175).
(D) Combined list of hazardous substances
prioritized as described in A-C, including HH +
ENVH (as described in (A), N = 478), EDC + PBT
+ vPvB + POP (as described in (B), N = 54),
REACH + PROP65 (as described in (C), N = 378);
with overlaps, the combined list includes the total
N = 608 of hazardous FCCdb substances priori­
tized based on selected authoritative sources of
hazard information.
Environmental Protection Agency, and from the 2018 UNEP report on
EDCs (UNEP, 2018), at least 95 more FCCdb substances are currently
being assessed or suspected to be EDCs of concern in the EU and/or
worldwide. Consideration of the TEDX inventory of putative EDCs,
defined as substances with potential endocrine disrupting properties
reported in the peer-reviewed publications, would have highlighted at
least 294 more potential EDCs among the FCCdb chemicals. However,
TEDX list cannot be considered authoritative due to its high uncertainty,
therefore it shall be considered only among the non-authoritative
sources as discussed later in Section 3.4.4.
The GHS classifications currently also do not cover persistencerelated hazards. Therefore, we used three authoritative sources to
address this gap, namely the PBT/vPvB assessments carried out in the
EU, the US EPA list of PBT substances, and the Stockholm convention’s
list of POPs. This analysis flagged 32 FCCdb substances in total (Table 2);
only 17 of these have already been prioritized based on the GHS-aligned
classifications (Fig. 2B). The assessment of persistence-related chemical
hazards is also an ongoing process. According to the ECHA’s PBT
assessment list, at least 43 additional FCCdb substances are currently
being assessed in this regard.
With overlaps, consideration of authoritative sources identifying
substances with endocrine disruption- or persistence-related hazards
prioritized 54 FCCdb substances, roughly half of which would not have
been highlighted based on GHS classifications alone (Fig. 2B, Supple­
mentary File 3).
classifications provided by either one of them for the final prioritization,
since this allowed to increase the coverage of globally sourced FCCs. In
total, 263 substances with HH sum hazard scores ≥ 10′ 000 and 266
substances with ENVH sum hazard scores ≥ 1000 were prioritized. With
a small overlap of 47 substances having priority sum hazard scores for
both HH and ENVH classification types, this amounts to 482 priority
hazardous substances for HH and/or ENVH identified based on GHSaligned hazard classifications (Fig. 2A, Table 2). The list of all sub­
stances prioritized based on this criterion is given in the Supplementary
File 3.
3.3.2. Prioritization based on endocrine disruption- and persistence-related
hazards
Because the GHS classifications do not consider endocrine disrup­
tion, we additionally covered this hazard by consulting several author­
itative sources dealing with EDC assessment and identification in the EU.
Currently, 20 FCCdb substances are officially recognized as EDCs under
the REACH legislation (i.e., these substances are added to the Candidate
list of SVHCs for authorization due to their endocrine disrupting prop­
erties harmful to human health and/or the environment). Two more
FCCdb substances are recognized as EDCs under the Biocides regulation
(Regulation (EU) No 528/2012). These twenty-two substances were
added to the list of prioritized hazardous FCCdb substances; only half of
them have already been prioritized based on the GHS classifications
(Fig. 2B). Importantly, the process of EDC identification is far from being
completed, with conclusive endocrine disruption assessment pending
for many more substances. As follows from the ECHA’s Endocrine dis­
ruptor assessment list, from the EDC lists compiled by the Danish
3.3.3. Prioritization based on inclusion on selected regulatory lists
The EU REACH list of substances of very high concern (SVHC), also
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Environment International 150 (2021) 106225
Fig. 3. Total numbers and overlaps between
FCCdb chemicals identified as substances of
potential concern based on selected nonauthoritative (predictive) sources of hazard
information. (A) Identification based on
predicted health hazards (HH) and environ­
mental hazards (ENVH) of significant
concern (total N = 1251), including (i) pre­
dicted globally harmonized system (GHS)aligned classifications, as extracted from the
Danish Environmental Protection Agency
(Danish EPA) database of advisory classifi­
cation, labeling and packaging (CLP) classi­
fications predicted by in silico modeling, for
HH including Carcinogenicity 2 (C), Muta­
genicity 2 (M) and Reproductive Toxicity 2
(R) classifications (predHH:CMR, N = 864)
and for ENVH (predENVH, N = 436), and (ii)
substances identified by van Bossuyt et al.
(2017) as potential genotoxicants based on in
silico modeling (predHH:genotoxicants vB,
N = 106). (B) Identification due to suspected
endocrine disruption- or persistence related
hazards (total N = 466), including (i) 95
potential endocrine disrupting chemicals
(EDCs) identified based on authoritative
sources such as European Union and UN
Environmental Programme and 367 putative
EDCs from The Endocrine Disruption Ex­
change list (potential EDC, total N = 406),
(ii) substances under assessment in the EU as
potential persistent, bioaccumulative and
toxic (PBT) or very persistent, very bio­
accumulative (vPvB) substances (potential
PBT/vPvB, N = 43), and (iii) substances
identified as persistent, mobile and toxic
(PMT) and/or very persistent, very mobile
(vPvM) in a 2019 assessment by the German
Environment Agency (Arp and Hale, 2019)
(potential PMT/vPvM, N = 45). (C) Overlap
between three groups of substances included
on the list of FCCdb substances of potential
concern identified based on selected nonauthoritative, predictive sources (total N =
1798), including (i) substances of potential
concern due to HH or ENVH, identified as in
(A) (predHH + ENVH, N = 1251), (ii) sub­
stances of potential concern due to endocrine
disruption- or persistence-related hazards,
identified as in (B) (potential EDC + PBT/
vPvB + PMT/vPvM, N = 466), and (iii)
substances included on the Substitute It
Now! (SIN) List maintained by the nongovernmental organization International
Chemical Secretariat (SIN List, N = 308). (D)
Overlap between the 608 hazardous sub­
stances prioritized based on selected
authoritative sources of hazard information
as described in Section 3.3.4 and 1798 sub­
stances of potential concern identified as in
(C).
called Candidate list of SVHCs for Authorization, includes 123 FCCdb
chemicals, and 36 of these substances are also on the REACH Authori­
zation list (Annex XIV). On the EU REACH Restriction list (Annex XVII),
255 FCCdb chemicals are found. With overlaps, 292 FCCs are listed on
these three lists of hazardous substances maintained under the REACH
legislation in the EU. The California Proposition 65 (Prop65) list in­
cludes 175 FCCdb chemicals, about half of which overlap with REACHhighlighted substances (Fig. 2C). Overall, the consideration of inclusion
on the selected regulatory lists of hazardous substances prioritized 378
FCCdb substances (Supplementary File 3), which are thus explicitly
recognized as hazardous under the examined European and/or US-based
regulatory acts, but nonetheless could possibly be used in FCMs/FCAs
worldwide, potentially contributing to human exposure.
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3.3.4. Combined list of hazardous FCCdb chemicals prioritized based on
authoritative sources
The sources of authoritative hazard information described above in
Sections 3.3.1–3.3.3 provided some hazard information for 1615 FCCdb
substances (13.9%) of 11′ 609 chemicals with CAS numbers. Using the
above-described criteria, 608 of these substances have been added to the
combined list of priority hazardous FCCs (Table 2, Fig. 2D). All priori­
tized substances are listed in the Supplementary File 3.
The largest numbers of hazardous substances are found on global
inventories for printing inks (377), plastics (325), and paper/board
(256), but the inventories for other materials also include significant
numbers of prioritized hazardous chemicals (Table 1). Printing inks,
plastics, and paper/board inventories also had the highest numbers of
unique substances included on the priority list. Fourteen prioritized
substances are found on 10 or more global FCM inventories, indicating
likely widespread use: formaldehyde (CAS 50-00-0, on 14 global in­
ventories), styrene and vinyl chloride (CAS 100-42-5 and CAS 75-01-4,
respectively, each on 12 global inventories), sodium tetraborate and
acrylonitrile (CAS 1330-43-4 and CAS 107-13-1, each on 11 global in­
ventories), and nine substances on 10 global inventories each: boric acid
(CAS 10043-35-3), ammonia (CAS 7664-41-7), ethyl acrylate (CAS 14088-5), 1,1-dichloroethylene (CAS 75-35-4), ethylene glycol (CAS 10721-1), silicon dioxide (CAS 7631-86-9), zinc oxide (CAS 1314-13-2),
bisphenol A (BPA, CAS 80-05-7), and epichlorohydrin (CAS 106-89-8).
based on in silico evidence alone. ENVH of highest concern (i.e., Chronic
Aquatic Toxicity Category 1, with or without Acute Aquatic Toxicity
Category 1) was predicted for 436 FCCdb chemicals; among them, 100
substances also had predicted CMR hazards (Fig. 3A).
A study using a different suite of in silico models has prioritized 106
potential genotoxicants among the substances used in paper and board
FCMs, including printing inks (Van Bossuyt et al., 2017, 2016). We
considered all 106 of these substances to also be substances of potential
concern for human health due to predicted genotoxicity. Sixty-eight of
these chemicals are in fact already included in the Danish database,
having Muta2 classification predicted for 36 chemicals and Carc2 clas­
sification predicted for another set of 36 chemicals, with an overlap of
23 chemicals between the two groups. Additional 19 of the potential
genotoxicants prioritized by Van Bossuyt et al and assessed in the Danish
study did not receive any genotoxicity-related classification in the latter.
This observation underscores the current lack of agreement between
different in silico models, suggesting the need to either externally vali­
date the reliability of the in silico models or routinely consider the pre­
dictions delivered by several different models in making the final
assessment calls (Van Bossuyt et al., 2018). All considerations described
above highlighted 1251 FCCdb substances as being of potential concern
due to predicted health or environmental hazards (Fig. 3A, Supple­
mentary File 4).
Among these 1251 substances, 515 have potential concerns for
genotoxicity and/or carcinogenicity based on the assessment by the
Danish EPA and Van Bossuyt et al. (2017). For 110 of these substances,
experimental data on genotoxicity from the EFSA’s OpenFoodTox
database are also available, and among them, 8 substances have “posi­
tive” genotoxicity indication from at least one of the studies recorded in
that database. These substances are 2,3-epoxypropanol (CAS 556-52-5),
methyleugenol (CAS 93-15-2), ether, bis(pentabromophenyl) (CAS
1163-19-5), Ponceau 3R (CAS 3564-09-8), epoxy silane (CAS 2530-838), 4-prop-1-enylveratrole (CAS 93-16-3), Solvent Red 23 (CAS 85-869) and Solvent Red 24 (CAS 85-83-6). Only the first four of these sub­
stances are already included among the 608 substances prioritized based
on authoritative sources of hazard information, and overall, only 41 of
the 515 potentially genotoxic and/or carcinogenic substances are
already included on the prioritized list, while 163 additional substances
have hazard classifications of lower severity or other hazard information
available in the consulted authoritative sources. The remaining 311
substances thus appear to have not yet been subject to an assessment by
the authoritative sources we have consulted, despite being suspected to
have a hazardous property of very high concern. Since most of the
authoritative sources consulted in this work originate from Europe or
Japan, it could be that some of these 311 FCCs appear to remain unas­
sessed because they are not used in these geographical regions. How­
ever, this seems not to be the case, since the majority (280) of these 311
substances do have indications of use in these geographical regions, i.e.,
they are mentioned on the FCC lists sourced either from Europe (202), or
Japan (26), or both (52). Similarly, from the 436 FCCdb substances for
which the Danish in silico assessment predicted the Aquatic Chronic 1
classification that indicates the highest level of ENVH concern, only 25
substances are included on the list of 608 substances prioritized based on
authoritative sources, and 126 additional substances have less severe
classifications or other hazard information available from the consulted
authoritative sources, with the remaining 285 substances likely unas­
sessed. Again, the majority (250) of these 285 substances have in­
dications of use in either Europe (198), or Japan (27), or both (25).
Overall, these findings demonstrate a considerable gap between regu­
latory and scientific assessments of hazardous chemicals.
Over half of the 515 potentially genotoxic and/or carcinogenic
FCCdb substances are included on the global inventory for food contact
printing inks (295 substances), with further considerable contribution
from plastics (160 substances), coatings (107 substances), and paper and
board FCMs (101 substances). Interestingly, 49 of these 515 substances
are included on the global inventory for food contact colorants, which is
3.3.5. Hazard information provided by additional authoritative sources
Three additional authoritative sources of hazard information dis­
cussed here were not used for prioritization but allowed further
exploring the availability of reliable hazard data for additional FCCdb
substances. The EFSA’s OpenFoodTox database compiles hazard infor­
mation for all chemicals that have been evaluated by EFSA since its
creation in 2002 for some sort of food-related use (Ceriani et al., 2018).
While this database lists only 152 of the prioritized 608 FCCdb sub­
stances, it also provides some hazard information for about a thousand
additional FCCdb substances which have not been covered by the
authoritative sources used for prioritization as discussed above
(Table 2). Thus, together with the substances included on the EU’s
Community Rolling Action Plan (CoRAP) list and on the US EPA’s Safer
Chemical Ingredients List, and considering the sources used for priori­
tization, all authoritative sources examined in this work provided some
hazard information for 3001 (26%) of the 11′ 609 CAS-identified FCCdb
substances (Table 2).
3.4. FCCdb chemicals’ hazards explored by selected non-authoritative
sources
Since the authoritative hazard information was available for only
about a quarter of FCCdb chemicals, we also consulted several nonauthoritative sources of information to gain an overview of suspected
or predicted hazards. This allowed us to highlight additional substances
of potential concern.
3.4.1. Substances of potential concern due to predicted health and
environmental hazards
The Danish Environmental Protection Agency (Danish EPA) main­
tains a database of over 50′ 000 chemicals for which GHS-aligned hazard
classifications have been predicted using several in silico models. From
this database, at least one prediction for HH or ENVH classification
could be found for 2889 FCCdb chemicals (Table 2). Among them, 864
FCCdb chemicals were considered to exhibit predicted HH of serious
concern, corresponding to predicted CMR classifications, i.e., Carcino­
genicity Category 2 (Carc2) predicted for 178 FCCs, Mutagenicity
Category 2 (Muta2) for 370 FCCs, and Reproductive Toxicity Category 2
(Repr2) for 441 FCCs, with overlaps. Note that Category 2 is the highest
possible severity grade that could be assigned in this type of assessment,
because Category 1 classifications for CMR properties are never assigned
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a relatively high proportion for a list containing only 316 substances in
total. Most of these 49 substances are also found on the global inventory
for printing inks (34 substances) and some on inventories for a few other
FCM types, but 9 substances are unique to the food contact colorants list,
including Pigment Red 7 (CAS 6471-51-8), Pigment Red 8 (CAS 641030-6), Pigment Red 10 (CAS 6410-35-1), Vat Yellow 26 (CAS 3627-472), Solvent Yellow 130 (CAS 26846-41-3), Sudan Red G (CAS 122955-6), N-(9,10-dihydro-9,10-dioxo-1-anthryl)[1,1′ -biphenyl]-4-carbox­
amide (CAS 5924-63-0), 12-oxo-12H-phthaloperinesulfanilide (CAS
75199-11-0), and 3,3′ -dichloro-indanthrone (CAS 130-20-1).
chemicals prioritized for substitution based on authoritative sources (see
Section 3.3.4). In contrast, only 35 out of 1251 substances of potential
concern identified based on in silico predicted HH or ENVH (see Section
3.4.1) are currently found on the SIN List (Fig. 3C). However, SIN List
includes 134 out of 466 substances identified as potential EDCs and/or
PBT/vPvB and/or PMT/vPvM substances (Fig. 3C), suggesting that this
resource could be particularly useful for further prioritizing the sub­
stances of potential concern with regard to endocrine disruption- or
persistence-related substances.
3.4.4. Combined list of FCCdb substances of potential concern identified
based on predictive sources
Based on the selection process outlined in Sections 3.4.1–3.4.3, 1798
FCCdb substances in total have been included on the combined list of
FCCdb substances of potential concern identified based mainly on nonauthoritative sources (Fig. 3C, Supplementary File 4). Among these
substances, 387 have already been included on the list of 608 hazardous
FCCdb substances prioritized based on authoritative sources of hazard
information (Fig. 3D). The reasons for why a particular substance has
both authoritative and predictive hazard data justifying its inclusion on
both lists could be manifold. For example, it could be that this sub­
stance’s hazard was first predicted and then confirmed by an authori­
tative source, as is the case for many substances included on the SIN list.
A predictive source could also be identifying a different additional
hazard which has not yet been assessed and/or classified by the
authoritative source. These details should be clarified for each substance
upon closer evaluation with regard to substitution options. For some of
the remaining 1411 substances currently included only on the list of
predicted substances of potential concern, authoritative hazard data
may become available relatively soon, e.g., in the case of EDCs and PBT
substances currently under assessment in the EU. At the same time, if
judged based on the current regulatory procedures, many other sub­
stances of potential concern identified here might gain regulatory
attention only once the now-lacking authoritative hazard data become
available. Thus, the identification of potential substances of concern
which lack authoritative data necessary to reach a definitive conclusion
on their hazards and substitution urgency indicates a significant
research and assessment need.
3.4.2. Substances of potential concern due to predicted endocrine disruption
or persistence-related hazards
As discussed in Section 3.3.2, consulted authoritative sources such as
EU and UNEP identify among the FCCdb chemicals at least 95 potential
EDCs and 43 potential PBT substances (see Section 3.3.2). In addition,
367 substances are identified as putative EDCs by the TEDX list. With
overlaps and together with 45 potentially persistent, mobile and toxic
(PMT) and/or very persistent, very mobile (PMT) substances identified
as described in the next paragraph, this amounts to 466 FCCdb sub­
stances identified to be substances of potential concern due to suspected
endocrine disruption- and/or persistence-related hazards (Fig. 3B).
Apart from bioaccumulation, mobility is now also considered an
important hazardous property that should be closely evaluated for
persistent substances. This is because chemicals which are both persis­
tent and mobile can remain in the aquatic environment for a long time
and can also be transported over long distances (Reemtsma et al., 2016).
The EU is currently considering the options for inclusion of the PMT and
vPvM criteria in its process for SVHC identification under REACH, but
the discussions have not been finalized yet. The most comprehensive
analysis on the topic available to date is the 2019 study by the German
Environment Agency (Arp and Hale, 2019), therefore we used it as a
source of information on predicted hazards to identify potential PMT or
vPvM substances within the FCCdb. Based primarily on data availability,
the agency has self-evaluated the quality of its assessments and corre­
spondingly labeled them as high-, middle-, and low-quality assessments.
In total, 198 of the FCCdb substances have been subject to one of these
three types of assessment, and the high-quality assessments identify 45
FCCdb substances to be of potential concern as PMT and/or vPvM
substance (Supplementary File 4). Consideration of the medium-quality
and low-quality assessments would have flagged additional 91 and 13
potential PMT/vPvM substances in the FCCdb, respectively, while for
the remaining substances the PM properties were not confirmed. Only
one substance among the 45 PMT and/or vPvM substances identified
with the highest reliability, namely the tetraethylammonium per­
fluoroctanesulfonate (CAS 56773-42-3), has also been recognized as a
PBT/vPvB in the EU, and only 10 of these 45 substances in total are
already included on the list of 608 substances prioritized based on
authoritative hazard information sources.
3.5. Over a quarter of FCCdb chemicals lack easily accessible public
hazard data
Only 4986 of 11′ 609 CAS-identified FCCdb chemicals (43%) have
some information in at least one of the above-listed hazard information
sources used for prioritization of 608 hazardous substances and/or
identification of 1798 substances of potential concern (Table 2). In order
to also consider the availability of hazard data reported in literature, we
additionally consulted the Toxicity Values (ToxVal) database compiled
by the US EPA and hosted at the CompTox chemistry dashboard (Wil­
liams et al., 2017). Currently, this database includes 55′ 878 chemicals
for which “772’721 toxicity values from 29 sources of data, 21’507 subsources, 4585 journals cited and 69’833 literature citations” are recor­
ded, thus providing a broad coverage of both governmental and aca­
demic sources of chemical toxicity data. Indeed, this database lists the
highest proportion of FCCdb chemicals (8328 substances in total, or
71.7%, Table 2). The extent of hazard information available for each
chemical is, however, very variable. For example, 1263 substances
(10.9%) have less than 10 data sub-sources recorded in the ToxVal
database, while 256 substances (2.2%) have 100 or more (up to 146)
recorded data sub-sources. Consideration of the data provided by the
ToxVal database increased the number of FCCdb chemicals with some
hazard data to 8711 (75%). For the remaining quarter (2898 substances)
of the 11’609 CAS-identified FCCs, no hazard data could be obtained
from any of the sources consulted in our analysis (Table 2). Together
with the 676 CFSAN-identified FCCs which lack a CAS identifier and
therefore could not be searched for in any of the public hazard
3.4.3. Substances of potential concern highlighted through the SIN list
The Substitute It Now! (SIN) list, maintained by the NGO ChemSec,
records chemicals that have been identified by ChemSec as exhibiting
hazardous properties that would justify their identification as an SVHC
according to the EU REACH criteria described in the REACH article 57.
The scientific robustness and validity of ChemSec assessments have been
recognized internationally (UNEP, 2018). For example, all but one of the
20 FCCdb substances that are recognized as EDCs under the REACH
legislation in the EU (see Section 3.3.2) are already included on the SIN
list. Similarly, 25 of the 32 substances prioritized due to persistent and
bioaccumulative properties (see Section 3.3.2) are also found on the SIN
list. Progressive companies have long recognized the value of this
resource and are known to use it to identify substitution candidates
ahead of future regulatory changes. In total, there are 308 SIN listidentified substances in the FCCdb, of which the majority (270 sub­
stances) are already included on the list of 608 hazardous FCCdb
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Environment International 150 (2021) 106225
information sources that we have consulted, this amounts to 3574
substances that make up 29.1% of all 12’285 FCCs currently included in
the FCCdb. These 3574 FCCs appear to have none or only very limited
hazard data available in the public domain that are readily accessible.
Most of the 676 CFSAN-identified FCCs appear on the US FDA’s In­
ventory of Indirect Additives used in Food Contact Substances or other
FDA sources on FCCs, allowing to assume their active use in FCMs
despite the absence of easily accessible hazard data. Among the 2898
CAS-identified FCCdb substances without hazard data, 218 substances
have been registered under EU REACH, 401 appear on the TSCA in­
ventory (though 254 currently labeled as “inactive”), and 648 sub­
stances are included on the NZIOC list. With overlaps, these sources
suggest the likelihood of a current commercial use in the European,
North American, or New Zealand/Australian markets for up to 1017 of
the 2898 substances lacking public hazard data. However, these sources
are not specific to food contact uses and indeed, many more substances
(1004) are included on the European FACET FCM list, 866 substances on
at least one of the US FDA’s four sources of information on substances
used in food contact, and 722 substances on the Japanese lists for
organic polymers. Together, this amounts to at least 2541 of the 2898
CAS-identified substances lacking hazard data but having high proba­
bility of actual use, particularly in FCMs. Printing inks, plastics, paper/
board, coatings, and adhesives FCMs appear to have the highest
numbers of chemicals with limited or absent public hazard data, with
29%, 33%, 22%, 21% and 17% of the 3574 hazard data lacking sub­
stances being assigned to the respective global inventories (with over­
laps, including both CAS- and CFSAN-identified subsets). Significant
knowledge gaps with regard to toxicity of direct and indirect food ad­
ditives used in the US have already been highlighted previously (Neltner
et al., 2013; Neltner and Maffini, 2014). With over a third of the datalacking CAS-identified chemicals being listed on the FACET FCM list,
the situation in Europe appears to be similar.
detailed hazard and exposure data, which are often unavailable. As we
have demonstrated here, authoritative hazard data are missing for the
majority of FCCdb substances, and for over a quarter no hazard data
could be found in any of the globally sourced major databases that we
have consulted. Furthermore, having to deal with this many substances,
the risk assessment task becomes rather unfeasible, and even more so if
NIASs (which are not included in the FCCdb) are also considered
(Muncke et al., 2017). The use of in vitro bioassays to assess the toxicity
of overall migrates or extracts from FCMs/FCAs is currently being
explored as an integrative approach allowing to address unknown sub­
stances and mixture toxicity (Bengtstroem et al., 2016; Rosenmai et al.,
2017; Severin et al., 2017; Zimmermann et al., 2019). However, this
approach still needs further improvements with regard to reproduc­
ibility, sample preparation and sensitivity, as well as human healthrelevance of bioassays to be included in the test panel, and interpreta­
tion of the results obtained (Groh and Muncke, 2017).
Meanwhile, regulation continues to rely on single-substance assess­
ment and management approaches that do not incorporate the most
current scientific understanding, which emphasizes the importance of
mixture toxicity, low-dose effects, and non-standard testing approaches
(Muncke et al., 2020, 2017; Vandenberg et al., 2019). We and others
have repeatedly highlighted that both the official recognition and the
management of hazardous substances are severely lagging behind aca­
demic science that has delivered both experimental and computational
toxicology data for many additional substances that are used but not yet
regulated in FCMs (Groh et al., 2019; Nerin et al., 2018; Van Bossuyt
et al., 2016). Indeed, consideration of selected non-authoritative sources
of hazard information led us to highlight further 1411 FCCdb substances
of potential concern in addition to the 608 hazardous substances already
prioritized based on authoritative information sources. In the long term,
these 1411 substances of potential concern should be researched further
to first confirm or disprove the suspected hazard properties and then to
carry out a substitution-focused assessment following similar consider­
ations as suggested above for the 608 prioritized substances.
Among the different FCM types, not only plastics and coatings but
also paper and board FCMs appear to be a significant source of haz­
ardous substances, even when printing inks are not considered (Rose­
nmai et al., 2017). The printing inks FCM type in fact includes the
highest number of identified hazardous substances so far, many of them
remaining unassessed (Van Bossuyt et al., 2016). In addition to printing
inks, paper-based FCAs can also contain coatings and adhesives, both
FCM types characterized by a high diversity of potentially hazardous
FCCs and rather little oversight to ensure their safe use. This lack of
transparency with regard to hazardous chemicals used in paper-based
FCAs is of concern, especially considering the current trend towards
increasing the use of paper-based products as alternative to single-use
plastics, and the common use of recycled paper materials in direct
contact with food in countries where this practice is not banned. Active
and intelligent materials represent another FCM group with surprisingly
little information publicly available on the identity and safety of their
chemical constituents, despite the continuously increasing production
volumes for the variety of applications reported for diverse ‘smart’
packaging products. Overall, more transparency on the side of producers
as well as concerted efforts on the side of regulators are urgently needed
in order to ensure systematic assessment and enforcement of FCM safety.
4. Conclusions
The FCCdb resource presented here currently lists 12′ 285 substances
that could possibly be intentionally used to make FCMs/FCAs world­
wide, thus demonstrating the large diversity of FCCs. Using several
authoritative sources of hazard information, we prioritized 608 haz­
ardous FCCdb substances as the most urgent candidates to be further
evaluated and targeted by substitution efforts. In the next steps, it should
first be confirmed that these FCCs are still in use, and if yes, then further
data on their regulatory status, use patterns, and exposure potential
should be collected and evaluated. This evaluation should consider,
among others, regulatory provisions for food contact use which are
already in place or are planned under different jurisdictions; regionspecific production and import volumes; use in and migration from
specific FCAs; types of food contact applications, e.g., disposable versus
reuse applications, or inclusion in recycling loops; other manufacturing
or life cycle characteristics which could be of relevance for substitution;
similarity of chemical structures or hazard classes; data on cooccurrence in the same articles and potential for mixture effects. Using
these and other criteria, the prioritized 608 substances can be split into
smaller, better actionable groups.
It can be argued that some of the hazardous FCCs will likely not be
present or will not migrate from the final FCA, and thus should be
‘exempt’ from substitution considerations. However, the hazards of
these chemicals should not be disregarded on the basis of the use phase
only, as the application of toxic chemicals in the production of FCMs/
FCAs also contributes to occupational exposure. Moreover, as the
economies worldwide strive towards more circularity and continued reuse of the scarce material resources, the need to keep toxic chemicals out
of the loop becomes increasingly apparent (Geueke et al., 2018).
It has been also suggested that the continuous use of hazardous
substances can be justified as long as the risks are properly assessed and
carefully managed. However, reliable risk assessment would require
Declaration of Competing Interest
The authors declare no conflict of interest. KG, BG, and JM are em­
ployees of Food Packaging Forum Foundation (FPF), a charitable foun­
dation dedicated to science communication and research on chemicals
in all types of food contact materials and articles. MVM and OVM have
project-based contracts for working with FPF and receive remuneration
for this role from FPF. They are also members of the FPF scientific
advisory board and they are not remunerated for this role but have
received travel reimbursement from FPF for attending its meetings. FPF
12
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Environment International 150 (2021) 106225
is funded by unconditional donations and project-based grants. All
current and past donors and funders of FPF are listed on its website
(https://www.foodpackagingforum.org/about-us/funding). Donors and
funders have no influence on the conception and execution of FPF’s
work.
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Acknowledgements
Work on this project was partially financed by grants from MAVA
Foundation and Valery Foundation. We thank the three anonymous
reviewers for their valuable insights.
Appendix A. Supplementary material
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.envint.2020.106225.
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