volume 119 | number 10 | October 2011 • Environmental Health Perspectives
Research | Children’s Health
Perfluorooctanoic acid (PFOA) is a synthetic
chemical that has been used in the manufac-
ture of fluoropolymers since the 1950s [U.S.
Environmental Protection Agency (EPA)
2009a] and may also result from the break-
down of a related group of chemicals called
fluorinated telomers (U.S. EPA 2009b).
Fluoropolymers are used in non stick cook-
ware and clothing made from waterproof,
breathable fabric (U.S. EPA 2009b).
PFOA and other perfluorinated com-
pounds (PFCs) with comparable industrial
uses—perfluorooctane sulfonate (PFOS),
perfluorohexane sulfonate (PFHxS), and
perfluorononanoic acid (PFNA)—are per-
sistent environmental pollutants that have
been detected worldwide in both wildlife and
humans, with higher exposure closer to urban-
ized and industrialized regions (Houde et al.
2006). In the U.S. general population, PFOA,
PFOS, and PFHxS were detected in all serum
samples from the 1999–2000 National
Health and Nutrition Examination Survey
(NHANES); PFNA was detected in 95% of
samples (Calafat et al. 2007a). NHANES
2003–2004 data showed minor reductions
in the percentage of samples with detectable
levels of PFOA, PFOS, and PFHxS, and the
geometric mean concentrations for these three
compounds dropped slightly (Calafat et al.
2007b). For PFNA, however, the percent-
age of serum samples with detectable levels
increased, and the geometric mean increased
from 0.5 ng/mL to 1.0 ng/mL, between
the NHANES waves. PFOA and PFOS,
the two most commonly studied PFCs,
have been detected in maternal and umbili-
cal cord blood (Inoue et al. 2004; Midasch
et al. 2007; Monroy et al. 2008) and breast
milk (Kuklenyik et al. 2004; So et al. 2006;
Tao et al. 2008a, 2008b; Volkel et al. 2008).
The serum elimination half-life for PFOA is
estimated at 2.3 years (Bartell et al. 2010) to
4 years (Olsen et al. 2007); for PFOS, 5 years
(Olsen et al. 2007); and for PFHxS, 8.5 years
(Olsen et al. 2007). A half-life estimate is not
available for PFNA.
Toxicology studies highlight the poten-
tial for PFCs to affect fetal growth and devel-
opment (reviewed by Lau et al. 2004, 2007;
Olsen et al. 2009). Rat pups prenatally exposed
to PFOS show delayed behavioral milestones
(Luebker et al. 2005), and delayed task learn-
ing has been noted in female pups pre natally
exposed to PFOS and maternal restraint
(Fuentes et al. 2007). The limited develop-
mental toxicology literature suggests possible
adverse effects of PFOA and PFOS on fetal
growth and viability and postnatal growth
(Butenhoff et al. 2004; Lau et al. 2004).
One epidemiologic study examined
developmental milestones in relation to PFC
exposure (Fei et al. 2008). In a substudy of the
Danish National Birth Cohort (n = 1,400),
early pregnancy plasma PFOA and PFOS
levels were essentially unrelated to motor or
mental development through 18 months of
age, although there were weak associations
between increased PFOS levels and sitting
without assistance or using wordlike sounds to
indicate wants (Fei et al. 2008). A single study
has examined the association between PFC
exposure and attention deficit/hyperactivity
disorder (ADHD) among children from the
1999–2000 and 2003–2004 NHANES and
reported increased odds of disease with higher
serum PFC levels (Hoffman et al. 2010).
ADHD is a relatively common neuro-
developmental disorder with suspected envi-
ronmental and genetic etiology (reviewed
by Aguiar et al. 2010; Banerjee et al. 2007;
Swanson et al. 2007). The disorder, generally
recognized by early school age, is character-
ized by developmentally inappropriate levels
of inattention, hyperactivity, and impulsivity
[Centers for Disease Control and Prevention
(CDC) 2010]. In the 2007 U.S. National
Survey of Children’s Health, the estimate
of parent-reported ADHD among children
4–17 years of age was 9.5%; 4.8% reported
both diagnosis and medication use (CDC
2010). Although prevalence estimates vary,
it is generally accepted that the prevalence
of this disorder is rising (Aguiar et al. 2010;
CDC 2010; Pastor and Reuben 2008). In
contrast, the prevalence of learning disorders
among children 6–17 years of age, estimated
at 8.7%, has been relatively stable from 1997
to 2006 (Pastor and Reuben 2008). Prenatal
Address correspondence to C.R. Stein, Department
of Preventive Medicine, Mount Sinai School of
Medicine, One Gustave L. Levy Place, Box 1057,
New York, NY 10029-6574 USA. Telephone: (212)
824-7083. Fax: (212) 996-0407. E-mail: cheryl.
This research was funded by the C8 class action
settlement agreement (Jack W. Leach, et al. v. E.I. du
Pont de Nemours & Company, no. 01-C-608 W.Va.,
Wood County Circuit Court, WV, USA) between
DuPont and plaintiffs. Funds were administered
by the Garden City Group (Melville, NY), which
reports to the court. Our work and conclusions are
independent of either party to the lawsuit. C.S. was
supported by the National Institute of Environmental
Health Sciences (K01 ES019156).
The authors declare they have no actual or poten-
tial competing financial interests.
Received 7 February 2011; accepted 10 June 2011.
Serum Perfluorinated Compound Concentration and
Attention Deficit/Hyperactivity Disorder in Children 5–18 Years of Age
Cheryl R. Stein1 and David A. Savitz2,3
1Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA; 2Department of Community Health,
and 3Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA
Background: Perfluorinated compounds (PFCs) are persistent environmental pollutants.
Toxicology studies demonstrate the potential for perfluorooctanoic acid (PFOA) and other PFCs to
affect human growth and development. Attention deficit/hyperactivity disorder (ADHD) is a devel-
opmental disorder with suspected environmental and genetic etiology.
oBjectives: We examined the cross-sectional association between serum PFC concentration and
parent or self-report of doctor-diagnosed ADHD with and without current ADHD medication.
Methods: We used data from the C8 Health Project, a 2005–2006 survey in a Mid-Ohio Valley
community highly exposed to PFOA through contaminated drinking water, to study non-Hispanic
white children 5–18 years of age. Logistic regression models were adjusted for age and sex.
results: Of the 10,546 eligible children, 12.4% reported ADHD and 5.1% reported ADHD
plus ADHD medication use. We observed an inverted J-shaped association between PFOA and
ADHD, with a small increase in prevalence for the second quartile of exposure compared with the
lowest, and a decrease for the highest versus lowest quartile. The prevalence of ADHD plus medica-
tion increased with perfluorohexane sulfonate (PFHxS) levels, with an adjusted odds ratio of 1.59
(95% confidence interval, 1.21–2.08) comparing the highest quartile of exposure to the lowest. We
observed a modest association between perfluorooctane sulfonate and ADHD with medication.
conclusions: The most notable finding for PFOA and ADHD, a reduction in prevalence at the
highest exposure level, is unlikely to be causal, perhaps reflecting a spurious finding related to the
geographic determination of PFOA exposure in this population or to unmeasured behavioral or
physiologic correlates of exposure and outcome. Possible positive associations between other PFCs
and ADHD, particularly PFHxS, warrant continued investigation.
key words: adolescent, attention deficit disorders, child, epidemiology, fluorocarbons, per-
fluorooctanoic acid. Environ Health Perspect 119:1466–1471 (2011). http://dx.doi.org/10.1289/
ehp.1003538 [Online 10 June 2011]
Perfluorinated compounds and ADHD
Environmental Health Perspectives • volume 119 | number 10 | October 2011
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