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Neurotoxicity of Ortho-Phthalates:
Recommendations for Critical Policy
Reforms to Protect Brain Development
in Children
Stephanie M. Engel, PhD, Heather B. Patisaul, PhD, Charlotte Brody, RN, Russ Hauser, MD, ScD, MPH, Ami R. Zota, ScD, MS, Deborah
H. Bennet, PhD, Maureen Swanson, MPA, and Robin M. Whyatt, DrPH
Robust data from longitudinal birth cohort studies and experimental studies of perinatally exposed animals
indicate that exposure to ortho-phthalates can impair brain development and increase risks for learning,
attention, and behavioral disorders in childhood. This growing body of evidence, along with known
adverse effects on male reproductive tract development, calls for immediate action.
Exposures are ubiquitous; the majority of people are exposed to multiple ortho-phthalates simulta-
neously. We thus recommend that a class approach be used in assessing health impacts as has been done
with other chemical classes. We propose critically needed policy reforms to eliminate ortho-phthalates from
products that lead to exposure of pregnant women, women of reproductive age, infants, and children.
Specific attention should be focused on reducing exposures among socially vulnerable populations such
as communities of color, who frequently experience higher exposures.
Ortho-phthalates are used in a vast array of products and elimination will thus necessitate a multi-
pronged regulatory approach at federal and state levels. The fact that manufacturers and retailers have
already voluntarily removed ortho-phthalates from a wide range of products indicates that this goal is
feasible. (Am J Public Health. Published online ahead of print February 18, 2021: e1–e9. https://doi.org/
10.2105/AJPH.2020.306014)
As experts in toxic chemicals and
neurodevelopment who are
members of Project TENDR (Targeting
Environmental Neuro-Development
Risks), we have determined that expo-
sure to ortho-phthalates can impair
child brain development and increase
children’s risks for learning, attention,
and behavioral disorders. There are robust
data from longitudinal birth cohort studies
conducted over the last decade that have
shown associations between prenatal ex-
posures to ortho-phthalates and attention-
deficit hyperactivity disorder (ADHD), other
behavioral problems, adverse cognitive
development including lower IQ, poorer
psychomotor development, and impaired
social communication.
This growing body of evidence, along
with the known adverse effects on male
reproductive tract development of
ortho-phthalates, calls for immediate
action. Given that general population
exposure is ubiquitous and is to a
mixture of multiple ortho-phthalates si-
multaneously, we recommend that as-
sessment of hazard use a class approach,
as has been done for a number of other
chemical classes. To protect child brain
development, ortho-phthalates need to
be removed from consumer products
that contribute to exposure of pregnant
women, women of reproductive age, in-
fants, and children. We summarize the
epidemiological evidence on adverse
neurodevelopmental effects following
prenatal exposure to ortho-phthalates,
discuss sources of exposure and what is
known about potential mechanisms, and
propose urgently needed reforms to
substantially reduce exposures to
ortho-phthalates over critical periods of
child brain development.
WHAT ARE PHTHALATES?
Ortho-phthalates are diesters of
phthalic acid and are the predominate
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ANALYTIC ESSAYS
type of phthalate used in commerce.
(For simplicity, we will refer to them as
phthalates.) They are high-production-
volume chemicals used most often as a
plasticizer in polyvinyl chloride (PVC) and
other plastics. Phthalates are used in
numerous consumer products, includ-
ing food production materials and
packaging; medical supplies and coat-
ings of medicines; flooring, wall cover-
ings, and other home materials; and
cosmetics and other personal care
products.
1
Approximately 4.9 million
metric tons are produced annually
worldwide (reviewed in Ejaredar et al.
2
).
The highest-production phthalates are
di-2-ethylhexyl phthalate (DEHP), diiso-
nonyl phthalate (DiNP), butylbenzyl
phthalate (BBzP), dibutyl phthalates
(DBPs), and diethyl phthalate (DEP).
3
Diet is a particularly important expo-
sure pathway for some phthalates, in-
cluding DEHP and DiNP.
4
Phthalates
have been shown to leach into food
from plastic equipment like tubing used
in commercial dairy operations, lid gas-
kets, food preparation gloves, conveyor
belts, and food packaging materials.
5
As
such, consumption of fast food and
other dining-out sources,
5
as well as li-
pophilic foods such as dairy,
4
can be
important dietary sources of phthalate
exposures.
Building products containing phtha-
lates, such as vinyl flooring and wall
coverings, have a large surface area
from which phthalates can migrate into
the indoor air and household dust, also
resulting in human exposure.
6
Histori-
cally, phthalates were added to chil-
dren’s toys, although use of multiple
phthalates in toys has been banned by
the Consumer Product Safety Commis-
sion (CPSC; see Box 1).
1,7
Phthalates including DEP and DBPs
are commonly used in cosmetics and
other personal care products, and are
sometimes used as excipients in medi-
cations and supplements (Box 1).
2
For
example, DEP and DBPs are used in a
wide range of personal care products
including nail polish, lotions, fragrances,
and hair-styling products.
41
Numerous
studies have found correlations be-
tween personal care product use and
the concentrations of phthalate me-
tabolites in urine.
41
Overall, women have
higher exposure to phthalates found in
personal care products than men, and
Black and Latina women have higher
exposure to certain phthalates com-
pared with White women, independent
of socioeconomic status.
42
Phthalates
are readily transferred from mother to
fetus during pregnancy.
2
US population exposure to phthalates
has changed in the last decade.
7
Expo-
sures to di-n-butyl phthalate (DnBP),
BBzP, and DEHP have declined, while
exposures to replacement phthalates
such as DiNP and diisobutyl phthalate
(DiBP) have increased. The observed
temporal trends are likely a reflection of
legislative activity and advocacy efforts
of nongovernmental organizations, as
well as changes by manufacturers and
retailers in response to consumer prefer-
ence (see the box on page e3).
7
EPIDEMIOLOGICAL
EVIDENCE OF
NEUROTOXICITY
Historically, most of the health concerns
and regulations pertaining to phthalates
were motivated by strong toxicological
evidence showing adverse antiandrogenic
effects on male reproductive tract de-
velopment.
1
More recently, an increasing
number of prospective epidemiological
studies have found associations between
prenatal exposure to phthalates and ad-
verse neurodevelopment in offspring.
43
A
recent systematic review of the human
data concluded that prenatal exposure to
DEHP, DBPs, DEP, and BBzP has an ad-
verse impact on cognitive and psycho-
motor development, internalizing and
externalizing behaviors, attention, gender-
related play behaviors, social responsive-
ness, and visual spatial abilities of chil-
dren.
43
As of 2019, there were more than
30 published studies that have measured
prenatal exposure to phthalates using
validated exposure biomarkers
43–49
or
environmental estimates of prenatal
exposure
50,51
in longitudinal cohorts as-
sembled from 11 different countries or
territories around the globe. Children
have been followed for altered neonatal
behavior or infant visual recognition
memory, cognitive development, behav-
ior, executive function, reciprocal social
behavior, gender-related play behaviors,
and for symptoms of, or clinical diagnosis
with, developmental disabilities including
autism and ADHD. Examples of key find-
ings from this extensive literature base are
discussed in the following paragraphs.
The most consistent pattern across
multiple studies is associations with
behaviors commonly associated with
ADHD (including hyperactivity, aggression/
defiance, and emotional reactivity),
43
def-
icits in executive function,
52,53
or ADHD
clinical diagnosis.
54
For example, a 2018
study nested within the Norwegian
Mother and Child Cohort leveraged a
linkage between this cohort and the
Norwegian National Patient Registry,
which collects all outpatient diagnoses
from specialty clinics. Engel et al. mea-
sured second-trimester urinary phtha-
lates and found that children of mothers
that fell in the highest quintile of pre-
natal exposure to DEHP metabolites
had almost 3 times the odds of being
diagnosed with ADHD as those with
mothers in the lowest quintile (odds
ratio [OR] = 2.99; 95% confidence in-
terval [CI] = 1.47, 5.49).
54
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Phthalates, particularly metabolites of
DBP and DEHP, have also been associ-
ated with more problem behaviors, as
estimated by validated inventory-based
behavioral rating scales in these largely
subclinical populations. For example,
Lien et al. reported that third-trimester
urinary concentrations of DnBP and
DEHP metabolites were associated with
more externalizing problems, more de-
linquent behaviors, and more aggressive
behaviors, as measured by the Child
Federal Regulatory, Manufacturer, and Retailer Action on Phthalates
I. Federal Regulatory Action
A. US Environmental Protection Agency (EPA)
·Set a drinking water standard for DEHP (6 ppb).
8
·Listed DEHP and DBP as hazardous air pollutants and as substances on the Toxic Release Inventory that must be reported to EPA if released into any media.
8
·Listed phthalates as hazardous waste if discarded as commercial chemical products under the Resource Conservation and Recovery Act.
8
·Recently designated 5 phthalates (DnBP, DiBP, BBzP, DEHP, and DCHP) as high-priority substances for risk evaluation under the Toxic Substances Control Act.
9
B. US Consumer Product Safety Commission
·Banned 8 ortho-phthalates from use in children’s toys and childcare articles: DEHP, DBP, BBzP, DINP, DiBP, DPENP, DHEXP, and DCHP.
10
The regulation is under
legal challenge by the National Association of Manufacturers, the American Chemistry Council, and other industry groups.
11
C. US Food and Drug Administration (FDA)
·Set maximum concentration of DEHP in bottled water at the same concentration that EPA had set in drinking water.
12
·Issued guidelines (but not regulation) recommending that DBP and DEHP be avoided as excipients in prescription and nonprescription products,
13
advised
manufacturers to label medical devices that contain DEHP,
14
and concluded that exposure to DEHP received by some infants from medical device–related
sources could be substantially greater than the agency’s estimate of the Tolerable Intake.
15
·Approved use of 28 phthalates as food additives in food contact articles.
16,17
Uses include as plasticizers, binders, coating agents, defoamers, and gasket
closures, in materials such as cellophane, paper and paperboard, and plastics.
·Has failed to meet the statutory deadline for final decisions on 3 recently submitted petitions that could substantially reduce dietary exposure to phthalates.
17
o Two were submitted by 11 environmental and public health organizations and requested that FDA strike from its existing regulations its approvals of all 28
phthalates as food additives in food contact articles, as the agency could no longer conclude that such use is safe, as is required by law.
17
o The third petition was submitted by the Flexible Vinyl Alliance and requested that FDA revoke its approval of 24 phthalates that the Alliance claims are no
longer used as food additives in food contact applications.
17
The industry petition did not include several approved uses of these phthalates and continued the
approval of DEHP, DINP, DCHP, and DIDP as food additives.
II. Examples of Voluntary Action by Retailers and Manufacturers
·Home Depot’s safer chemicals policy includes restrictions on phthalates as a class in vinyl flooring and wall-to-wall carpet.
18,19
·Lowe’s, Lumber Liquidators, and Menards have taken action to remove phthalates as a class from vinyl flooring.
19,20
·Apple has removed phthalates as a class from almost all products.
21
·Hewlett Packard has removed multiple phthalates from commercial personal computer products and a lesser number from other products.
22
·IKEA has removed phthalates from a number of its products.
23
·Mohawk,
24
Tarkett,
24
SC Johnson,
25
and Steelcase
26
have restricted use of phthalates in some products, including household products.
·Ahold Delhaize, the fourth largest grocery chain in the United States (with 2000 stores including Food Lion, Giant Food, Giant/Martin’s, Hannaford, and Stop &
Shop) recently announced restrictions on phthalates and other chemicals in its own branded products in the following categories: all grocery, baby food and
infant formula, and formulated laundry products, as well as personal care, cosmetic, and baby products.
27,28
·CVS Health,
29
Loblaw,
29
Rite Aid,
30
and Walmart
31
are also reducing the use of phthalates in beauty and personal care products and household products with
the goal of elimination.
·Sephora set a goal to reduce high-priority chemicals including 8 phthalates by 50% over the next 3 years.
32,33
·Panera Bread has replaced vinyl gloves, which must be softened with phthalates or other plasticizers, with safer alternatives such as polyethylene gloves that
require no such chemical additives.
33
III. Examples of Health Care Organization and Medical Supplier Actions
·Dignity Health,
34
Hackensack Meridian Health,
35
and Kaiser Permanente
36
have a stated preference for products made without phthalates.
·Warner Chilcott recently brought a new product to market, Delzicol (mesalamine), which does not contain DBP in the medication coating.
37
In totality, these examples demonstrate the feasibility of reformulating a vast array of products to remove phthalates. Cited references can help inform steps
necessary in selection of safer alternatives when replacing phthalates.
38–40
Note. BBzP = butylbenzyl phthalate; DBP = dibutyl phthalate; DCHP = dicyclohexl phthalate; DEHP = di-2-ethylhexyl phthalate; DHEXP = di-n-hexyl phthalate;
DiBP = diisobutyl phthalate; DIDP = di-isodecyl phthalate; DINP = diisononyl phthalate; DnBP = di-n-butyl phthalate; DPENP = di-n-pentyl phthalate; and
ppb = parts per billion.
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Behavior Checklist, in a population of 8-
year-old children in Taiwan.
55
Also using
the Child Behavior Checklist and leveraging
a US-based multicenter pregnancy cohort
enrolled in California, Minnesota, Missouri,
and Iowa, Kobrosly et al. reported that
third-trimester urinary DiBP metabolites
were associated with more inattention,
rule-breaking behavior, aggression, and
conduct problems.
56
DEHP and BBzP
metabolites were also linked with altered
behavior that was in some cases sex-spe-
cific. Another recent study found an
association between prenatal exposure
to the sum of low-molecular-weight
phthalates (which includes metabolites
of DBPs and DEP) and hyperactivity,
attention problems, and anxiety at the
age of 16 years.
49
In addition, phthalates have been
associated with altered child executive
functions using both rater-based and
performance-based assessments. Ex-
ecutive functions are higher-order cog-
nitive processes that support goal-
directed behaviors and are typically
impaired in children with ADHD. Factor-
Litvak et al. reported that prenatal DBP
metabolites were associated with
poorer working memory in a birth co-
hort enrolled in New York City and ad-
ministered the Wechsler Intelligence
Scale for Children-IV at age 7 years.
53
Engel et al. reported that prenatal me-
tabolites of DBP were associated with
poorer working memory on the Behav-
ior Rating Inventory of Executive Func-
tion.
52
Factor-Litvak et al. also found that
prenatal metabolites of DBPs were as-
sociated with a significant linear reduc-
tion in child IQ. Overall, child IQ was 7
points lower in the highest versus lowest
quartile of DBP exposure. DBP metab-
olites were also associated with index-
specific decrements in processing
speed, perceptual reasoning, and verbal
comprehension.
53
Maternal urinary
concentrations of BBzP metabolites
were also associated with reductions in
child perceptual reasoning.
53
It is important to note that the liter-
ature is not entirely consistent, partic-
ularly among studies that focus on
cognitive development during infancy
and early childhood. Among these
studies, there is often a lack of overlap in
the specific metabolites implicated, the
gender most affected, or the direction of
the relationship. Even among studies of
neurobehavior, not all have found
associations,
48,49,57,58
and some have
found associations primarily with inter-
nalizing domains.
59,60
Some of these
differences may be attributable in part
to differences in the study designs, in-
cluding the age of the child at testing, the
gestational age at urine sample collec-
tion, and the instruments used for
assessing neurodevelopmental outcomes
measures. In addition, early studies of
phthalates and neurobehavior summed
phthalate metabolites into low- and high-
molecular-weight groupings, which makes
it difficult to compare results to those
reporting findings on individual phthalates,
particularly in light of temporal changes
of the contribution of speci ficphthalates
to the overall exposure mixture.
Despite these differences, the weight
of evidence strongly supports a rela-
tionship between certain phthalates and
altered neurobehavioral development.
This interpretation is additionally sup-
ported by the Chronic Hazard Advisory
Panel for the CPSC, which concluded that
poorer neurodevelopment test scores
are generally associated with higher
maternal prenatal urinary concentrations
of metabolites of DEHP, DBPs, and DEP,
and that human exposure to these
phthalates should be reduced.
1
Consis-
tent with the systematic review by Zhang
et al.,
43
a 2015 review also concluded that
prenatal exposures to DEP, BBzP, DEHP,
and DBPs were associated with adverse
cognitive and behavioral outcomes in
children, including lower IQ and prob-
lems with attention, hyperactivity, and
poorer social communication.
2
EXPERIMENTAL EVIDENCE
OF NEUROTOXICITY
Studies of gestational and early life ex-
posure in animal models, which have
mostly focused on DEHP, are generally
consistent with the observations from
epidemiological studies. The most con-
sistently observed effects include hy-
peractivity, anxiety and depressive
behaviors, and cognitive impairments
including impacts on learning and
memory.
61
Disruption of the organiza-
tion and function of the hypothalamic–
pituitary–gonadal axis by phthalates
known to inhibit fetal testosterone
production is also frequently reported.
61
A particularly compelling study showed
that rats perinatally (both before and
after birth) exposed to a human-relevant
phthalate mixture displayed lower cog-
nitive flexibility in a set-shifting task, an
outcome that correlated with fewer
synapses in the prefrontal cortex.
62
Sensitive windows of exposure span
pre- and postnatal life through adoles-
cence
63
including puberty
64–66
and
possibly adulthood,
67–70
which is un-
surprising given that complex structures
including the prefrontal cortex, hippo-
campus, and cerebellum undergo sig-
nificant development well into early
adulthood.
Consistent with the epidemiological
findings, animal outcomes are fre-
quently sex-specific. It is known that
many phthalates are antiandrogenic
1
although antiestrogenic effects have
also been reported in vitro.
71
It has been
hypothesized that the differential effect
of phthalates on neurobehavioral
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outcome by sex seen in many studies
may result from disrupted fetal testos-
terone production. Critically, unlike ro-
dents in which testosterone is
aromatized to estrogen in the develop-
ing brain and then acts via estrogen
receptors to masculinize the male brain,
in genetically male humans testosterone
acts primarily via the androgen recep-
tor.
70
Thus, while the phenomenon of
sex-specificeffects may be conserved
across species, specificeffects within sex
may vary based on taxonomical differ-
ences in steroid hormone function.
Phthalates can also modulate aromatase
activity in the developing brain, which can
interfere with estrogen synthesis.
72,73
This is of concern because estrogen plays
a critical role in brain plasticity and other
developmental refinements,
74
and there
is also growing evidence that estrogen
synthesis can be extragonadal, including
in the brain.
75
The hippocampus and, consequently,
aspects of neural plasticity, cognitive
flexibility, anxiety-like behavior, learning,
and memory, are thought to be partic-
ularly vulnerable to phthalates. For ex-
ample, male mice prenatally exposed to
DEHP had evidence of oxidative stress,
neuronal loss, and neuroinflammation
in the hippocampus as adults, along with
elevated anxiety behavior and impaired
recognition memory.
76,77
Similarly, male
rats perinatally exposed to DEHP had
impaired dendritic complexity in the
hippocampus, particularly in CA1 pyra-
midal neurons.
78
A recent review of the phthalate lit-
erature discussed several additional
potential mechanisms to explain the
epidemiological and animal toxicity lit-
erature.
3
Disruption of thyroid hormone
pathways is one potential mechanism of
interest, given that thyroid hormone is
essential for brain development. There
is also evidence of altered ion
homeostasis including calcium signaling,
peroxisome proliferator-activated re-
ceptors activation, and lipid metabolism,
particularly in the hippocampus.
In summary, multiple longitudinal
studies of human prenatal phthalate
exposure have found evidence of al-
tered neurobehavioral development.
These findings are of concern especially
in light of the supporting evidence from
experimental studies and a growing
understanding of the mechanisms
whereby phthalates may adversely af-
fect fetal brain development. Given the
widespread exposures to phthalates,
including among women and children,
and the limited existing US regulations,
none of which focus on pregnant
women, health-protective regulatory
actions are required to eliminate these
potentially harmful exposures.
RECOMMENDATIONS FOR
SENSIBLE POLICY
REFORMS
Mounting evidence on the impacts of
phthalates on children’s brain develop-
ment compels meaningful actions to
eliminate exposure for women of re-
productive age, pregnant women, in-
fants, and children. As discussed, human
exposure to phthalates ranges from
foods to building materials to medical
products, pharmaceuticals, cosmetics,
and other personal care products.
Therefore, reducing human exposure
necessitates a multipronged approach
through regulations at the federal and
state levels, as well as through voluntary
action on the part of retailers and
manufacturers.
To date, federal regulation of phtha-
lates in the United States has been
minimal with several exceptions, in-
cluding restrictions on 8 phthalates in
children’s toys and childcare articles
(Box 1). We strongly urge both federal
and state agencies to move rapidly to
eliminate phthalate use. Specific atten-
tion should be focused on reducing
exposures among socially vulnerable
populations such as communities of
color, who frequently experience
higher exposures.
42
States should not
wait for the federal government to act,
as state action can galvanize federal
regulation. It is encouraging that volun-
tary action on the part of manufacturers,
retailers, and health care organizations
has removed phthalates from a wide
range of products (Box 1). Consumer
pressure is critical to motivate additional
manufacturers and retailers to act, as
well as to encourage federal and state
regulation.
We recommend that the evaluation of
hazards of phthalates use a class ap-
proach as has been done for other
classes of chemicals (e.g., organophos-
phate pesticides, dioxin-like com-
pounds) and as has recently been
recommended by a National Academy
of Sciences report on organohalogen
flame retardants.
79,80
This approach is
appropriate given that general pop-
ulation exposure is to mixtures of
phthalates, coupled with the fact that
phthalates have similarities in chemical
structures, metabolism, and biological
activity, including disruption of
multiple endocrine systems, and
have common health outcomes, in-
cluding adverse effects on child neuro-
development and male reproductive
tract development, as well as other
adverse effects.
Following are 5 critical
recommendations for reducing phtha-
late exposures:
1to reduce dietary exposure,
2to reduce exposure from medical
supplies and medication,
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3to reduce exposure from personal
care products and other household
products,
4to reduce exposure from a broad
range of other products including
building materials, and
5to reduce risk of regrettable
substitution.
Dietary
The US Food and Drug Administration
(FDA) must remove from its existing
regulations its approvals of all 28
phthalates for use in food packaging
and other materials that come in con-
tact with food. There is no longer any
basis for the agency to conclude that
there is “reasonable certainty of no
harm”from these uses, which is the
legal standard for safety of food contact
materials under the federal Food, Drug,
and Cosmetic Act (see 21 CFR [updated
September 19, 2019]), which governs
FDA’s actions. All of the phthalates that
have been associated with adverse
child neurodevelopment, discussed
previously, are currently approved by
FDA for food contact use.
Until the FDA takes action to protect
the food supply from phthalates, the
food industry, including producers,
processors, retailers, and restaurant
chains, should investigate, identify, and
remove sources of phthalates from their
food products.
Medical Supplies and
Medication
The use of phthalates in medications
and medical devices also falls under FDA
jurisdiction. While FDA has published
guidelines to address many of these
sources (Box 1), the agency must pro-
mulgate regulations to eliminate their uses.
Personal Care and Other
Household Products
Authority to regulate phthalates in cos-
metics (which are defined broadly to
include many personal care products)
also falls under FDA jurisdiction. How-
ever, the agency’s authority is much less
comprehensive and health protective
than its authority to ensure the safety of
food or drugs. This needs to be rectified
by congressional action.
The CPSC has authority to ensure the
safety of consumer products and is to be
commended for eliminating a number of
phthalates from children’s toys. How-
ever, the agency must also take action
to prohibit the sale of other phthalate-
containing products that fall under its
jurisdiction.
In addition to federal action, elimina-
tion of phthalates from personal care
and household products requires action
on the part of states, manufacturers,
and retailers.
Personal care and household prod-
ucts must be labeled if they contain
phthalates so consumers can make in-
formed decisions to avoid these sub-
stances if desired.
Building Materials and Other
Products
The US Environmental Protection
Agency (EPA) must use its authority
under the Toxic Substances Control Act
(TSCA; 15 USC Ch 53 [2016]) to regulate
phthalates. EPA has recently embarked
on a multiyear process for evaluating the
risk of several phthalates under TSCA.
The agency must broaden this effort
using a class approach in assessing
health impacts. Furthermore, EPA
should aggressively exercise its author-
ity to regulate the manufacture, import,
processing, distribution in commerce,
disposal, and known and reasonably
foreseeable uses of phthalates.
Regrettable Substitution
Assessment to identify safer alternatives
to phthalates must consider adverse
effects to human health and the envi-
ronment as well as societal impacts
along with performance and costs.
80
This is critical given the potential for
regrettable substitution and the avail-
ability of lower-hazard alternatives (see
Box 1 for resources on approaches for
selecting safer alternatives). No phtha-
late should be used as a substitute for
another phthalate, as has already been
done with DiNP for DEHP. In addition,
PVC plastics should be replaced with
safer materials that do not require
plasticizers. The substitution of safer
alternatives for phthalates is critical
given the risk these chemicals pose to
child brain development.
CONCLUSION
Substantial evidence links exposure to
phthalates with increased risks for child
learning, attention, and behavioral
problems. We therefore recommend
that phthalates be eliminated from
products that may lead to exposure of
women of reproductive age, pregnant
women, infants, and children. As dis-
cussed, this will necessitate a multi-
pronged approach through regulations
at the federal and state levels, as well as
through voluntary action on the part of
retailers and manufacturers. However,
given that manufacturers have already
successfully removed phthalates from a
wide range of products, including food,
medicine and medical supplies, per-
sonal care products, and other house-
hold and building materials (Box 1), we
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believe the goal of phthalate elimination
is achievable.
ABOUT THE AUTHORS
Stephanie M. Engel is with the Department of Epi-
demiology, Gillings School of Global Public Health,
University of North Carolina at Chapel Hill. Heather
B. Patisaul is with the Department of Biological
Sciences, Center for Human Health and the Envi-
ronment, North Carolina State University, Raleigh.
Charlotte Brody is with Healthy Babies Bright Fu-
tures, Charlottesville, VA. Russ Hauser is with the
Department of Environmental Health at the Harvard
T. H. Chan School of Public Health, Boston, MA. Ami
R. Zota is with the Department of Environmental
and Occupational Health, George Washington
University Milken School of Public Health, Wash-
ington, DC. Deborah H. Bennet is with the Depart-
ment of Public Health Sciences, School of Medicine,
University of California at Davis. Maureen Swanson
is with The Arc of the United States, Washington, DC.
Robin M. Whyatt is with the Department of Envi-
ronmental Health Sciences, Mailman School of
Public Health, Columbia University, New York, NY.
CORRESPONDENCE
Correspondence should be sent to Stephanie M.
Engel, PhD, 135 Dauer Drive, Gillings School of
Global Public Health, CB# 7435, Chapel Hill, NC
27599-7435 (e-mail: stephanie.engel@unc.edu).
Reprints can be ordered at http://www.ajph.org by
clicking the “Reprints”link.
PUBLICATION INFORMATION
Full Citation: Engel SM, Patisaul HB, et al. Neuro-
toxicity of ortho-phthalates: recommendations for
critical policy reforms to protect brain development
in children. Am J Public Health. Published online
ahead of print February 18, 2021: e1–e9.
Acceptance Date: October 15, 2020.
DOI: https://doi.org/10.2105/AJPH.2020.306014
CONTRIBUTORS
All authors contributed equally to this article in
conceptualization and drafting of all components.
ACKNOWLEDGMENTS
We acknowledge that authors of this article have
received funding from the following entities: The
National Institute of Environmental Health Sciences:
P30ES010126 (S. M. E.), R01ES021777 (S. M. E.),
P30ES023513 (D. H. B.), P30ES025128 (H. P.), and
R01ES009718 (R. H.); the John Merck Fund (C. B.,
M. S.); the Passport Foundation, Ceres Trust, and
Pediatric Epilepsy Research Foundation (M. S.);
theClarenceE.HellerCharitableFoundation
(C. B.); the Marisla Foundation; and the Forsythia
Foundation (A. Z.).
CONFLICTS OF INTEREST
The authors report no conflicts of interest.
HUMAN PARTICIPANT PROTECTION
This is a review article and, thus, institutional board
review was not required.
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