Abstract
Our
purposes with this policy statement and its accompanying technical
report are to review and highlight emerging child health concerns
related to the use of colorings, flavorings, and chemicals deliberately
added to food during processing (direct food additives) as well as
substances in food contact materials, including adhesives, dyes,
coatings, paper, paperboard, plastic, and other polymers, which may
contaminate food as part of packaging or manufacturing equipment
(indirect food additives); to make reasonable recommendations that the
pediatrician might be able to adopt into the guidance provided during
pediatric visits; and to propose urgently needed reforms to the current
regulatory process at the US Food and Drug Administration (FDA) for food
additives. Concern regarding food additives has increased in the past 2
decades, in part because of studies in which authors document endocrine
disruption and other adverse health effects. In some cases, exposure to
these chemicals is disproportionate among minority and low-income
populations. Regulation and oversight of many food additives is
inadequate because of several key problems in the Federal Food, Drug,
and Cosmetic Act. Current requirements for a “generally recognized as
safe” (GRAS) designation are insufficient to ensure the safety of food
additives and do not contain sufficient protections against conflict of
interest. Additionally, the FDA does not have adequate authority to
acquire data on chemicals on the market or reassess their safety for
human health. These are critical weaknesses in the current regulatory
system for food additives. Data about health effects of food additives
on infants and children are limited or missing; however, in general,
infants and children are more vulnerable to chemical exposures.
Substantial improvements to the food additives regulatory system are
urgently needed, including greatly strengthening or replacing the
“generally recognized as safe” (GRAS) determination process, updating
the scientific foundation of the FDA’s safety assessment program,
retesting all previously approved chemicals, and labeling direct
additives with limited or no toxicity data.
Abbreviations:
- BPA —
- bisphenol A
- FDA —
- US Food and Drug Administration
- FFDCA —
- Federal Food, Drug, and Cosmetic Act
- GRAS —
- generally recognized as safe
Introduction
Today,
more than 10 000 chemicals are allowed to be added to food and food
contact materials in the United States, either directly or indirectly,
under the 1958 Food Additives Amendment to the 1938 Federal Food, Drug,
and Cosmetic Act (FFDCA) (public law number 85-929). Many of these were
grandfathered in for use by the federal government before the 1958
amendment, and an estimated 1000 chemicals are used under a “generally
recognized as safe” (GRAS) designation process without US Food and Drug
Administration (FDA) approval.1
Yet, suggested in accumulating evidence from nonhuman laboratory and
human epidemiological studies is that chemicals used in food and food
contact materials may contribute to disease and disability, as described
in the accompanying technical report and summarized in Table 1.
Children may be particularly susceptible to the effects of these
compounds, given that they have higher relative exposures compared with
adults (because of greater dietary intake per pound), their metabolic
(ie, detoxification) systems are still developing, and key organ systems
are undergoing substantial changes and maturation that are vulnerable
to disruptions.2
In this policy statement and accompanying technical report, we will not
address other contaminants that inadvertently enter the food and water
supply, such as aflatoxins, polychlorinated biphenyls, dioxins, metals
including mercury, pesticide residues such as DDT, and vomitoxin. In
this statement, we will not focus on genetically modified foods, because
they involve a separate set of regulatory and biomedical issues.
Caffeine or other stimulants intentionally added to food products will
not be covered.
TABLE 1
Summary of Food-Related Uses and Health Concerns for the Compounds Discussed in This Statement
The
potential for endocrine system disruption is of great concern,
especially in early life, when developmental programming of organ
systems is susceptible to permanent and lifelong disruption. The
international medical and scientific communities have called attention
to these issues in several recent landmark reports, including a
scientific statement from the Endocrine Society in 2009,42 which was updated in 2015 to reflect rapidly accumulating knowledge3; a joint report from the World Health Organization and United Nations Environment Program in 201343; and a statement from the International Federation of Gynecology and Obstetrics in 2015.44 Chemicals of increasing concern include the following:
bisphenols, which are used in the lining of metal cans to prevent corrosion45;
phthalates,
which are esters of diphthalic acid that are often used in adhesives,
lubricants, and plasticizers during the manufacturing process17;
nonpersistent
pesticides, which have been addressed in a previous policy statement
from the American Academy of Pediatrics and, thus, will not be discussed
in this statement46;
perfluoroalkyl chemicals (PFCs), which are used in grease-proof paper and packaging47; and
perchlorate,
an antistatic agent used for plastic packaging in contact with dry
foods with surfaces that do not contain free fat or oil and also present
as a degradation product of bleach used to clean food manufacturing
equipment.48
Additional
compounds of concern discussed in the accompanying technical report
include artificial food colors, nitrates, and nitrites.
Environmentally
relevant doses (ie, low nanomolar concentrations that people are likely
to encounter in daily life) of bisphenol A (BPA)4 trigger the conversion of cells to adipocytes,9 disrupt pancreatic β-cell function in vivo,49 and affect glucose transport in adipocytes.9–11
Phthalates are metabolized to chemicals that influence the expression
of master regulators of lipid and carbohydrate metabolism, the
peroxisome proliferator-activated receptors,21
with specific effects that produce insulin resistance in nonhuman
laboratory studies. Some studies have documented similar metabolic
effects in human populations.22 Some phthalates are well known to be antiandrogenic and can affect fetal reproductive development.18,19,50 Authors of recent studies have linked perfluoroalkyl chemicals with reduced immune response to vaccine27,28 and thyroid hormone alterations,29,51,52 among other adverse health end points. Perchlorate is known to disrupt thyroid hormone34 and, along with exposures to other food contaminants, such as polybrominated diphenyl ethers,53–55 may be contributing to the increase in neonatal hypothyroidism that has been documented in the United States.56 Artificial food colors may be associated with exacerbation of attention-deficit/hyperactivity disorder symptoms.57 Nitrates and nitrites can interfere with thyroid hormone production40 and, under specific endogenous conditions, may result in the increased production of carcinogenic N-nitroso compounds.37,38
Racial and ethnic differences in food additive exposures are well documented.58,59 Higher urinary concentrations of BPA have been documented in African American individuals,60 and BPA concentrations have been inversely associated with family income.61 Given that obesity is well recognized to be more prevalent among low-income and minority children in the United States,62 disproportionate exposures to obesogenic chemicals such as BPA partially explain sociodemographic disparities in health.
Regulatory Framework for Direct and Indirect Food Additives
The
Food Additives Amendment of 1958 was passed as an amendment to the
FFDCA and was used to provide specific guidance for food additives. The
legislation required a formal agency review, public comment, and open
rulemaking process for new chemical additives. It also contained an
exemption for common food additives, such as oil or vinegar, when used
in ways that were GRAS.63 Under these specific scenarios, a formal rulemaking process was not required.
Despite
this framework, there remain substantial gaps in data about potential
health effects of food additives. A recent evaluation of 3941 direct
food additives revealed that 63.9% of these had no feeding data
whatsoever (either a study of the lethal dose in 50% of animals or an
oral toxicology study). Only 263 (6.7%) had reproductive toxicology
data, and 2 had developmental toxicology data.64
This
lack of data on food additives stems from 2 critical problems within
the food regulatory system. First, the GRAS process, although intended
to be used in limited situations, has become the process by which
virtually all new food additives enter the market. Consequently, neither
the FDA nor the public have adequate notice or review. The Government
Accountability Office conducted an extensive review of the FDA GRAS
program in 2010 and determined that the FDA is not able to ensure the
safety of existing or new additives through this approval mechanism.65
Concerns also have been raised about conflicts of interest in the
scientific review of food additives leading to GRAS designation. A
recent evaluation of 451 GRAS evaluations voluntarily submitted to the
FDA revealed that 22.4% of evaluations were made by an employee of the
manufacturer, 13.3% were made by an employee of a consulting firm
selected by the manufacturer, and 64.3% were made by an expert panel
selected by the consulting firm or manufacturer. None were made by a
third party.66
Second, the FDA does not have authority to obtain data on or reassess the safety of chemicals already on the market.1
This issue is of great importance and concern for chemicals approved
decades ago on the basis of limited and sometimes antiquated testing
methods. For instance, some compounds, such as styrene and eugenol
methyl ether, remain approved for use as flavoring agents, although they
have been subsequently classified as reasonably anticipated to be human
carcinogens by the US National Toxicology Program.67
Further
compounding the problems noted above are other shortcomings within
agency procedures. For example, the FDA does not regularly consider
cumulative effects of food additives in the context of other chemical
exposures that may affect the same biological receptor or mechanism,
despite their legal requirement to do so.68–70
Synergistic effects of chemicals found in foods are also not
considered. Synergistic and cumulative effects are especially important,
given that multiple food contaminants, such as polybrominated diphenyl
ethers, perchlorate, and organophosphate pesticides, can disrupt various
aspects of the thyroid hormone system.71 Dietary interactions may also be important, given that iodine sufficiency is essential for thyroid function.72
In
addition, the FDA’s toxicological testing recommendations have not been
updated on the basis of new scientific information. Testing guidelines
for food contact materials are based on estimated dietary exposure, and
only genotoxicity tests are recommended for exposures estimated to be
less than 150 µg per person per day, regardless of body weight.73
Thus, toxicological testing may not account for behavioral or other end
points that may be more likely to be impaired by early life exposures,
especially to additives that act at low doses to disrupt endocrine
pathways. Furthermore, these guidelines may not be adequately protective
for children, given that they may receive higher relative doses than
adults because of their lower body weights.
Recommendations for Pediatricians and the Health Sector
It is difficult to know how to reduce exposures to many of these chemicals, but some recommendations are cited here.74–76
Insofar as these modifications can pose additional costs, barriers may
exist for low-income families to reduce their exposure to food additives
of concern. Pediatricians may wish to tailor guidance in the context of
practicality, especially because food insecurity remains a substantial
child health concern. Pediatricians also can advocate for modernization
of the FFDCA, as described in the subsequent section, which is of unique
importance for low-income populations who may not be as readily able to
reduce exposure to food additives.
Prioritize
consumption of fresh or frozen fruits and vegetables when possible, and
support that effort by developing a list of low-cost sources for fresh
fruits and vegetables.
Avoid processed meats, especially maternal consumption during pregnancy.
Avoid microwaving food or beverages (including infant formula and pumped human milk) in plastic, if possible.
Avoid placing plastics in the dishwasher.
Use alternatives to plastic, such as glass or stainless steel, when possible.
Look
at the recycling code on the bottom of products to find the plastic
type, and avoid plastics with recycling codes 3 (phthalates), 6
(styrene), and 7 (bisphenols) unless plastics are labeled as “biobased”
or “greenware,” indicating that they are made from corn and do not
contain bisphenols.
Encourage hand-washing before handling foods and/or drinks, and wash all fruits and vegetables that cannot be peeled.
Recommendations for Policy Makers
Just
as the American Academy of Pediatrics had recommended principles for
the modernization of the Toxic Substances Control Act (TSCA) to
strengthen regulation of chemicals in nonfood products to protect
children’s health,77 the Academy endorses previously described priority areas for improvements to the food additive regulatory program78
and provides additional recommendations below, some of which could be
accomplished by the FDA, whereas others may require congressional action
to change the current law.
Recommendations for Government
The
GRAS process is in need of substantial revision. A more robust and
transparent process of evaluation is needed, including additional
requirements for toxicity testing before approval of chemicals for the
marketplace. The GRAS system should be revised as soon as possible and
should fully document and disclose conflicts of interest in the
evaluation process.
The FDA
should leverage expertise and technical evaluations from other agencies
to gather missing data and identify knowledge gaps, while the current
GRAS process remains in place.
The FDA should establish requirements for prioritization and retesting of previously approved chemicals.
Congress
should provide the FDA authority to collect information about the use
of food additives and to require additional data from the industry when
gaps in knowledge and potential safety concerns are raised.
There
should be dedicated resources for research and testing that will allow
for a more effective evidence-based database to support a revised FDA
safety review process.
The
FDA should update the scientific foundation for the FDA safety
assessment process, including but not limited to the following: expand
the scope of recommended testing battery to cover endocrine-related and
neurobehavioral effects, ensure adequate safety factors for pregnant and
breastfeeding women and additional vulnerable populations, and develop
strategies to integrate emerging testing techniques.
The
FDA should consider cumulative and mixture effects from dietary
sources, including other additives and contaminants that interact with
relevant biological pathways.
The
FDA should establish requirements for labeling of additives with
limited or no toxicity data and those not reviewed for safety by the
FDA.
The federal government
should encourage provisions that ensure transparency and public access
to information, including potential conflicts of interest.
The
changes described above can be used to help restore public confidence
in the safety of food additives. The FDA can and should make
improvements within the scope of current agency authority. Ultimately,
congressional action may be required to reform the food additives
regulatory process. To aid in this process, the pediatrician community
should come together on these issues to advocate for the protection of
children’s health.
Lead Authors
Leonardo Trasande, MD, MPP, FAAP
Rachel M. Shaffer, MPH
Sheela Sathyanarayana, MD, MPH
Council on Environmental Health Executive Committee, 2016–2017
Jennifer A. Lowry, MD, FAAP, Chairperson
Samantha Ahdoot, MD, FAAP
Carl R. Baum, MD, FACMT, FAAP
Aaron S. Bernstein, MD, MPH, FAAP
Aparna Bole, MD, FAAP
Carla C. Campbell, MD, MS, FAAP
Philip J. Landrigan, MD, FAAP
Susan E. Pacheco, MD, FAAP
Adam J. Spanier, MD, PhD, MPH, FAAP
Leonardo Trasande, MD, MPP, FAAP
Alan D. Woolf, MD, MPH, FAAP
Former Executive Committee Members
Heather Lynn Brumberg, MD, MPH, FAAP
Bruce P. Lanphear, MD, MPH, FAAP
Jerome A. Paulson, MD, FAAP
Liaisons
John M. Balbus, MD, MPH – National Institute of Environmental Health Sciences
Diane E. Hindman, MD, FAAP – Section on Pediatric Trainees
Nathaniel G. DeNicola, MD, MSc – American College of Obstetricians and Gynecologists
Ruth Ann Etzel, MD, PhD, FAAP – US Environmental Protection Agency
Mary Ellen Mortensen, MD, MS – Centers for Disease Control and Prevention/National Center for Environmental Health
Mary H. Ward, PhD – National Cancer Institute
Footnotes
- Address correspondence to Leonardo Trasande, MD, MPP, FAAP. E-mail: Leonardo.Trasande@nyumc.org
This
document is copyrighted and is property of the American Academy of
Pediatrics and its Board of Directors. All authors have filed conflict
of interest statements with the American Academy of Pediatrics. Any
conflicts have been resolved through a process approved by the Board of
Directors. The American Academy of Pediatrics has neither solicited nor
accepted any commercial involvement in the development of the content of
this publication.
Policy
statements from the American Academy of Pediatrics benefit from
expertise and resources of liaisons and internal (AAP) and external
reviewers. However, policy statements from the American Academy of
Pediatrics may not reflect the views of the liaisons or the
organizations or government agencies that they represent.
The
guidance in this statement does not indicate an exclusive course of
treatment or serve as a standard of medical care. Variations, taking
into account individual circumstances, may be appropriate.
All
policy statements from the American Academy of Pediatrics automatically
expire 5 years after publication unless reaffirmed, revised, or retired
at or before that time.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING:
Dr Trasande is supported by R01ES022972, R56ES027256, UG3OD023305,
R01DK100307, and U01OH011299. Ms Shaffer is supported by T32ES015459.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health or the Centers of Disease Control and Prevention.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
- Copyright © 2018 by the American Academy of Pediatrics
