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Impacts of food contact chemicals on human health
Research on Chemical Intermediates publishes current research articles and concise dynamic reviews on the properties,
structures and reactivities of intermediate species in all the various domains of chemistry.
The journal also contains articles in related disciplines such as spectroscopy, molecular biology and biochemistry,
atmospheric and environmental sciences, catalysis, photochemistry and photophysics. In addition, special issues dedicated to
specific topics in the field are regularly published.
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
APIs and Intermediates. 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.
We, as scientists working on developmental biology, endocrinology, epidemiology, toxicology, and environmental and public
health, are concerned that public health is currently insufficiently protected from harmful exposures to food contact
chemicals (FCCs). Importantly, exposures to harmful FCCs are avoidable. Therefore, we consider it our responsibility to bring
this issue to the attention of fellow scientists with relevant expertise, 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 initiated on this topic and that
the issue of chemical safety of food packaging becomes a central aspect in the discussions on sustainable packaging.
Food contact chemicals (FCCs) are the chemical constituents 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
coenzymes and nucleotides series [3]. Indeed, for some
FCCs there is evidence for human exposure from biomonitoring [4,5,6,7,8,9,10,11], although some FCCs may have multiple uses
and also non-food contact exposure pathways.
When food contact material regulations were first developed, it had been generally assumed that low-level chemical
exposures, i.e. exposures below the toxicologically 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 endocrine disrupting chemicals can contribute to
adverse health effects [14,15,16,17,18,19,20]. In addition, chemical mixtures can play a role in the development of adverse
effects [21,22,23,24], 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 aspect 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 scientific shortcomings of the current chemical risk assessment for food contact materials in Europe and the US [1]. For
example, in the European Union (EU) the regulation EU 10/2011 includes a list of authorized substances for the manufacture of
plastic materials and articles in contact with food and, for some of the fine
chemicals, 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 substances 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 example 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 chemicals does not sufficiently protect public health.
Therefore, we would like to bring the following statement to the attention of policy makers and stakeholders, especially
those currently working on the issue of packaging 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 involves 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 packaging in the circular economy, which aims at minimizing waste, energy and resources use [28].
Therefore, we provide 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.
Chemicals can transfer from food contact materials and articles into food. This phenomenon is known as migration and has
been studied since the 1950s [29,30,31,32,33]. All types of food contact materials may exhibit chemical migration, but the
types of migrating
Sitagliptin Phosphate Monohydrate CAS 654671-77-9 and their levels differ significantly.
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 contact 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 contact articles [68]. In the
United States (US), 10,787 substances 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].
All migrating FCCs have inherent toxicity properties that can cause different effects at different doses and are related
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 the available toxicity data are limited [67]. Moreover, endocrine disruption, as a specific
hazard of concern, is not routinely assessed for 2,4,5-Trifluorophenyl Acetic Acid CAS 209995-38-0 migrating from food contact articles,
although some chemical migrants are known endocrine disruptors [73,74,75,76,77].
Exposure data are commonly based on assumptions or estimates – 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.
Research on Chemical Intermediates publishes current research articles and concise dynamic reviews on the properties,
structures and reactivities of intermediate species in all the various domains of chemistry.
The journal also contains articles in related disciplines such as spectroscopy, molecular biology and biochemistry,
atmospheric and environmental sciences, catalysis, photochemistry and photophysics. In addition, special issues dedicated to
specific topics in the field are regularly published.
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
APIs and Intermediates. 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.
We, as scientists working on developmental biology, endocrinology, epidemiology, toxicology, and environmental and public
health, are concerned that public health is currently insufficiently protected from harmful exposures to food contact
chemicals (FCCs). Importantly, exposures to harmful FCCs are avoidable. Therefore, we consider it our responsibility to bring
this issue to the attention of fellow scientists with relevant expertise, 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 initiated on this topic and that
the issue of chemical safety of food packaging becomes a central aspect in the discussions on sustainable packaging.
Food contact chemicals (FCCs) are the chemical constituents 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
coenzymes and nucleotides series [3]. Indeed, for some
FCCs there is evidence for human exposure from biomonitoring [4,5,6,7,8,9,10,11], although some FCCs may have multiple uses
and also non-food contact exposure pathways.
When food contact material regulations were first developed, it had been generally assumed that low-level chemical
exposures, i.e. exposures below the toxicologically 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 endocrine disrupting chemicals can contribute to
adverse health effects [14,15,16,17,18,19,20]. In addition, chemical mixtures can play a role in the development of adverse
effects [21,22,23,24], 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 aspect 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 scientific shortcomings of the current chemical risk assessment for food contact materials in Europe and the US [1]. For
example, in the European Union (EU) the regulation EU 10/2011 includes a list of authorized substances for the manufacture of
plastic materials and articles in contact with food and, for some of the fine
chemicals, 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 substances 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 example 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 chemicals does not sufficiently protect public health.
Therefore, we would like to bring the following statement to the attention of policy makers and stakeholders, especially
those currently working on the issue of packaging 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 involves 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 packaging in the circular economy, which aims at minimizing waste, energy and resources use [28].
Therefore, we provide 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.
Chemicals can transfer from food contact materials and articles into food. This phenomenon is known as migration and has
been studied since the 1950s [29,30,31,32,33]. All types of food contact materials may exhibit chemical migration, but the
types of migrating
Sitagliptin Phosphate Monohydrate CAS 654671-77-9 and their levels differ significantly.
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 contact 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 contact articles [68]. In the
United States (US), 10,787 substances 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].
All migrating FCCs have inherent toxicity properties that can cause different effects at different doses and are related
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 the available toxicity data are limited [67]. Moreover, endocrine disruption, as a specific
hazard of concern, is not routinely assessed for 2,4,5-Trifluorophenyl Acetic Acid CAS 209995-38-0 migrating from food contact articles,
although some chemical migrants are known endocrine disruptors [73,74,75,76,77].
Exposure data are commonly based on assumptions or estimates – 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.