Do these links make sense from">
Valid reasons to link autoimmunity and environment? Explain....


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"Given what you read in the above article, do you think there are valid reasons to link autoimmunity and environment? Explain.
Do these links make sense from an immunological perspective? Give specific examples in your answer.
What other explanation can you think of to explain the increases in autoimmunity seen in the human population?
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should include UV exposure, even absent
specific FDA requirements.
Our resin data (resins P1. P2, P3, P4
P19, and P18) cited by Kelce and Borgert
came from at least three replications of stress­
ing, extraction, and EA assays. As described
in our “Methods” and “Supplemental
Material,” the assay variance was very small
SEs were typically smaller than the diameter
of the data points of the graphed means.
The whole series of 49 assays was repeated
only once, but no extract exhibited EA, more
recent extracts of the same plastics confirm
our original results.
Kelce and Borgert noted that colorants are
“embedded” in plastics. However, “bound”
colorants in plastic compounds can and do
readily leach from plastics. They are additives
which—like most additives—are only rarely
chemically bound to polymers. Hence, con­
cerns about all additives are warranted because
any can leach from a plastic product.
Regarding broader issues, the objective
of our paper was to quantify the prevalence
of xeno­ strogen release from commonly used
plastic products. These data are significant in
part to help assess the risk of such products
to human health and environmental con­
tamination. Kelce and Borgert cite Charles
et al. (2007), who examined some inter­
actions between a small set of phyto­ strogens
and xeno­ strogens. The limited negative
results of that study have been contradicted
by dozens of other studies (e.g., Patisaul and
Jefferson 2010). However, our objective was
not to establish definitive links between pub­
lic health issues, environmental pollution
and exposure to xenoestrogens. This relation­
ship is an active research area, and it will take
many years to obtain definitive answers.
Kelce and Borgert’s concerns about the
paucity of epidemiological data correlating
EA exposure via use of plastics with adverse
human health effects is analogous to the longstanding controversy for tobacco, which is
now highly regulated, largely because increas­
ing numbers of epidemiological studies
correlated smoking with heart disease and
lung cancer. For decades, it was common to
hear tobacco industry spokes­ ersons argue
that “[epidemiological] correlation does not
mean causation” and demand that molecu­
lar, cellular, and/or systemic mechanisms be
extensively demon­ trated before any action
regulatory or otherwise, be taken. One rarely
hears spokespersons for the chemical and
plastics industry make this argument for
release of chemicals having EA from plastics
because the mechanisms by which tobacco
has its effects are still much less well known
compared to mechanisms by which chemi­
cals having EA produce adverse health and
environ­ ental effects. Instead, we hear
“Where are the epidemiological correlations?”
Environmental Health Perspectives? •?
Those correlations are fewer (but not non­
existent) than for tobacco at this relatively
young stage of the field, but the number of
such publications is rapidly increasing. In
the meantime, our study and hundreds to
thousands of other in vitro studies demon­
strate that chemicals having EA have eas­
ily measurable effects on all sorts of human
cells (including MCF-7 cells). Most scientists
in this field believe that such results suggest
adverse health effects in humans and that
as such data continue to be gathered, these
correlations will become as compelling as did
those for the impact of tobacco smoking on
public health.
Legislators, consumers, manufacturers
and scientists must judge current industry
practices in this area based on available data.
Reasonable people can differ. The American
Chemistry Council takes the position that
until definitive studies consistently show
health and environmental hazards from
chemi­ als with EA leaching from plastic
products, no industry action need be taken.
We disagree. Plastic items are essential con­
sumer products, but we argue that they need
to be made safer. Our most recent data show
that there is very little extra expense to pro­
duce safer plastics that do not leach chemi­
cals having EA, that is, it costs very little at
this time to avoid a potential health risk.
C.Z.Y. is employed by, and owns stock in
CertiChem (CCi) and PlastiPure (PPi). S.I.Y.
and D.J.K. are employed by PPi. V.C.J. has
no financial interests in CCi or PPi, but he
was principal investigator for a subcontract at
Northwestern Medical School to help develop the
MCF-7 assay on NIH grant P30 CA051008
awarded to CCi. G.D.B. owns stock in and is
the founder and chief excutive officer of CCi and
the founder and chief scientific officer of PPi. All
authors had freedom to design, conduct, interpret, and publish research uncompromised by
any controlling sponsor.
Chun Z. Yang
George D. Bittner
CertiChem Inc.
Austin, Texas
Stuart I. Yaniger
Daniel J. Klein
PlastiPure Inc.
Austin, Texas
V. Craig Jordan
Lombardi Comprehensive Cancer Center
Georgetown University Medical Center
Washington, DC
Charles GD, Gennings C, Tornesi B, Kan HL, Zacharewski TR
Gallapudi BB, et al. 2007. Analysis of the interaction of
phytoestrogens and synthetic chemicals: an in vitro/
in vivo comparison. Toxicol Appl Pharmacol 218:280–288.
FDA (Food and Drug Administration). 2002, 2007. Guidance
for Industry: Preparation of Premarket Submissions
volume 119 | number 9 | September 2011
for Food Contact Substances: Chemistry Recom­
menda­ ions. Available:
ucm081818.htm [accessed 10 August 2011].
Patisaul HB, Jefferson W. 2010. The pros and cons of phyto­
estrogens. Front Neuroendocinol 31(4):400–419
doi:10.1016/j.yfme.2010.03.003 [Online 27 March 2010].
Wagner M, Oehlmann J. 2010 Endocrine disruptors in bottled
mineral water: estrogenic activity in the E-screen. J Steroid
Biochem Mol Biol, doi:10.1016/j.jsbrnb.2010.10.007 [Online
2 November 2010].
Yang CZ, Yaniger SI, Jordan VC, Klein DJ, Bittner GD. 2011.
Most plastic products release estrogenic chemicals
a potential health problem that can be solved. Environ
Health Perspect 119:989–996, doi:10.1289/ehp.1003220
[Online 2 March 2011].
Environmental Factors
Develop Different Patterns
of Immune Disease
I read with interest the article by Schmidt
(2011) on the sprawling explosion of auto­
immune diseases and its link to environ­ ental
exposure. Schmidt (2011) summarized the
problematic state of the field: Systemic auto­
immune diseases are common but thought
rare, their clinical identification is far from the
medical school description, and they continue
to be identified as an auto­ ntibody–target–
manifestation scheme. Experience shows that
a patient develops different auto­ ntibodies
through the lifespan, with different clinical
patterns within each phase, deeper investiga­
tion shows that organ auto­mmune disease is
in fact systemic. Likewise, allergy, food intol­
erance, cancer, and immuno­ eficiency (all
broad diseases that are immune in nature)
cross and share auto­mmunity. This suggests
that immature immune systems are promoted
and prevented from natural selection in the
era of anti­ iotics, but they pay the cost of fos­
tered health dysfunctions or diseases exposed
to the current complex hostile environment.
I noticed this complex scenario in a sur­
vey of 22 patients reporting sick building
syndrome (Blasco 2011). Although reported
data was limited to auto­mmune cases and
the involved substances were not yet identi­
fied, I found that the same environment trig­
gered and worsened other immune dis­ rders.
The health of two patients with asthma
inexplicably worsened when they started to
work in the building. One patient developed
gyneco­ogical cancer, another patient, who
had a past history of Hodgkin’s lymphoma
developed chronic fever and fatigue again
that lasted 3 years, until she was relocated.
Some of the patients reported new adult onset
of clinical intolerance of milk or other foods
and one patient was positive in a breath test
for lactose intolerance. A review of family
histories revealed that in 20% of the patients
more than one direct relative was affected by
cancer. Personnel records showed that allergy
A 379
was present in 59% of the patients, recurrent
infections during childhood were common
20% required amigdalectomy. One patient
suffered rheumatic fever, one patient had not
been effectively immunized after repeated
hepatitis vaccines, and another had defective
CD4 and suffered recurrent pneumo­ occal
It would be surprising if these illnesses
did not share a common root in the immune
system. Schmidt (2011) underlined rising
prevalence rates of auto­mmunity and dis­
cussed causes. I believe that this trend is rele­
vant in general to immune disorders because
of different reactions within the same scope
of lymphocyte dysfunction in response to
our new aggressive environment.
The author declares that he has no actual or
potential competing financial interests.
Luis M. Blasco
Hospital Marqués de Valdecilla
Santander, Spain
Blasco LM. 2011. Sick building syndrome and autoimmunity.
Lupus 20:544–546.
Schmidt CW. 2011. Questions persist: environmental factors in autoimmune disease. Environ Health Perspect
Dietary Intervention and DEHP
Rudel et al. (2011) reported a surprising
reduction in metabolites of bis(2-ethyl­ exyl)
phthalate (DEHP) in their dietary interven­
tion study, considering that—to the best of
the industry’s knowledge—the plasticizer is
no longer used in the food packaging prod­
ucts that the authors removed from the sub­
jects’ dietary routine. Although we question
the public health significance of a potential
reduction of a few micrograms per liter of
DEHP metabolites, we initially saw the study
as having the potential to improve our under­
standing of how low-level exposure to DEHP
suggested by the presence of the metabolites
may be occurring. Unfortunately, in review­
ing the Rudel et al. analysis more thoroughly
we were disappointed.
The 56% reduction in mean levels sug­
gested by Rudel et al. (2011) is based on the
concentration of DEHP metabolites—before
correcting for creatinine levels. With little
more than a sentence, Rudel et al. dismissed
the accepted practice of correcting for crea­
tinine levels to account for the substantial
variability in an individual’s urine output.
They suggested that such adjustment may
“bias associations between urine metabo­ite
concentrations and age or sex” (Rudel et al.
A 380
2011) without explaining that the correction
is widely used in urinary bio­ onitoring (by
the Centers for Disease Control and most
others) to improve the comparability of meas­
ure­ ents across individuals.
To their credit, Rudel et al. (2011) did
conduct a compari­ on of the creatinines
adjusted levels of DEHP metabolites and
found no statistically significant difference in
the mean levels of two of the three metabo­
lites before and after dietary intervention.
The authors did not report the change in
the adjusted levels of the third metabolite in
the article.
The authors also did not address the
variability in preintervention levels among
the study participants. The presence of two
individuals with very high metabolite levels
clearly skewed the mean value upward and
consequently, exaggerated the significance of
the intervention. Although Table 2 of Rudel
et al. (2011) provides the minimum, mean
and maximum values, the variability is best
seen in their Supplemental Material, Figure 3
(doi:10.1289/ehp.1003170), and on Silent
Spring Institute’s web site (Silent Spring
Institute 2011). It is unfortunate that Rudel
et al. (2011) chose not to address the vari­
ability in their article—and a bit surprising—
because the post­ ntervention increase in
DEHP metabolites was significantly lower
than the reported decrease (16% versus 56%).
The author is employed by the American
Chemistry Council to represent the manufacturers
of phthalates, including DEHP.
Stephen P. Risotto
American Chemistry Council
Washington, DC
Rudel RA, Gray JM, Engel CL, Rawsthorne TW, Dodson RE
Ackerman JM, et al. 2011. Food packaging and bisphenol A
and bis(2-ethylhexyl) phthalate exposure: findings from a
dietary intervention. Environ Health Perspect 119:914–920
doi:10.1289/ehp.1003170 [Online 30 March 2011].
Silent Spring Institute. 2011. Phthalate Levels Decline during
3-Day Fresh Food Diet. Available: http://www.silentspring.
org/images/our_research/DEHP_results.jpg [accessed
12 August 2011].
Dietary Intervention and DEHP
Reduction: Rudel et al. Respond
Steven Risotto, representing phthalate
manufacturers for the American Chemistry
Council (ACC), commented on our study
that found a 3?day diet with limited food
packaging reduced participants’ average
bis(2-ethyl­ exyl) phthalate (DEHP) expo­
sure by > 50% (Rudel et al. 2011).
Risotto’s statement that creatinine adjust­
ment by normalization is accepted practice
is misleading. Creatinine normali­ a­ ion is
z t
appropriate in a longitudinal study if the
daily creatinine excretion of the partici­
pants remains approximately constant. That
assumption is not reasonable in a dietary
intervention because short-term changes in
diet can strongly influence creatinine levels
(Kesteloot and Joossens 1993). In our article
(Rudel et al. 2011), we addressed urinary
dilution by including creatinine as a vari­
able in the mixed-effects model that estimates
exposure reduction from the intervention, as
currently recommended by researchers at the
Centers for Disease Control and Prevention
(Barr et al. 2005). Our analysis showed sig­
nificant decreases of 53–56% in the three
DEHP metabo­ites. Because creatinine nor­
malization is common, we also included nor­
malized results. Creatinine levels dropped
significantly during the intervention, indicat­
ing that creatinine normalization artificially
reduced the observed change. Nonetheless
results showed a 42–45% decrease in all
three DEHP metabolites, the decrease was
statistically significant for the most abun­
dant metabolite, MEHHP (mono-(2-ethyl5-hydroxy­ exyl) phthalate).
Risotto also questions whether DEHP
reductions are attributable to two individu­
als with high initial exposures. However, we
reported the decreases in geometric means
which are not strongly influenced by a
few high values. After removing these two
participants, we still observed decreases of
37–42% in the geometric means of DEHP
metabolites, and reductions in the two most
abundant metabolites remain statistically sig­
nificant. Removing participants with high
pre­ntervention exposures is appropriate if
an unknown exposure may have covaried
with the inter­ ention, but because the two
highest exposures were in different families
such confounding seems unlikely.
As to why DEHP metabolite levels
dropped during the intervention but did
not increase significantly after the interven­
tion—as discussed in detail in our article
(Rudel et al. 2011)—the discrepancy may be
attributable to the different-length “washout
periods” (


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