A Measure for Mothers
Model Predicts Lactational Transfer of PCB-153
Breastfed infants sit at the top of the food chain for the simple rea-
son that their nourishment comes from other humans. Through
biomagnification, environmental chemicals such as polychlorinated
biphenyls (PCBs) are passed up the food chain to the nursling.
Although epidemiologic studies have established an association
between prenatal PCB exposures and neurodevelopmental and
neurobehavioral problems, the potential health risks of xenobiotic
exposures via human milk are less clear and remain an area of
intense research interest [see “Contaminants in Human Milk:
Weighing the Risks against the Benefits of Breastfeeding,” EHP
116:A426–A434 (2008)]. Researchers have now developed a physi-
ologically based pharmacokinetic model of PCB-153 in women to
predict the transfer of this compound via lactation [EHP
116:1629–1634; Redding et al.].
PCB-153 was selected for study because it is the most prevalent
PCB congener in human tissues. To predict the concentration of
PCB-153 in human milk, physiological parameters were obtained
from a Taiwanese cohort and from reference values in published
studies. Partition coefficients were estimated based on chemical
structure and the lipid content in various body tissues as reported
in the literature: liver, fat, mammary tissue, and the “rest of the
body” (an average of brain, skin, and muscle), as well as a mixed
blood compartment.
The investigators predicted the acquired body burden of PCB-
153 from birth over a 25-year period on the basis of estimates of
exposure via diet using data from Japanese population studies.
They then compared the model’s predictions with measurements
from published studies in multiple countries.
Blood and tissue concentrations for a 25-year-old woman gen-
erated by the model were found to fall within ranges reported in
the literature, assuming that dietary intake of PCB-153 was the
principal source of this chemical in human milk. Additionally, the
researchers demonstrated the use of the model for reverse dosime-
try, also referred to as “exposure reconstruction,” for possible expo-
sure scenarios in Canadian Inuits, who consume extremely high
levels of PCB-153 through their traditional high-fat diet.
This human, population-scale lactational model for PCB-153
is the first to successfully predict a range of results that encompass
human biomonitoring data of milk PCB-153 content from all
over the world. The primary value of this model will be its ability
to describe the distribution, absorption, metabolism, and elimina-
tion of PCB-153 in nursing women. The new tool could also be
useful for reverse dosimetry modeling to enable retrospective
analyses of potential health effects of PCB exposures in breastfed
individuals. –M. Nathaniel Mead
A 532 VOLUME 116
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NUMBER 12
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December 2008 • Environmental Health Perspectives
Angling for Thyroid Answers
Study Links PBDEs to Hormone Disruption in
Male Sport-Fish Consumers
Levels of polybrominated diphenyl ethers (PBDEs) measured in
human samples have increased in recent years, but the health effects
of these compounds are not well studied. A group of persistent pol-
lutants similar in structure to polychlorinated biphenyls (PCBs),
PBDEs are thought to affect endocrine function, but this relation-
ship has only been examined in several small studies. A new study
significantly expands this knowledge base by analyzing PBDE expo-
sure among a large cohort of male sport-fish consumers and conclud-
ing that these exposures are associated with increased thyroglobulin
antibodies and increased thyroxine (T
4
) in adult males independent
of PCB exposure [EHP 116:1635–1641; Turyk et al.].
The study examined 405 adult males who consumed sport fish
from the Great Lakes during the early 1990s. Researchers gathered
data on the subjects’ levels of fish consumption, medical diseases,
and use of medications, and took serum samples that were tested for
PBDEs, PCBs, and DDE, a metabolite of DDT that may affect thy-
roid hormones. Total and free T
4
and triiodothyronine (T
3
) were
measured in serum and urine.
PBDE concentrations were positively associated with increased
T
4
and reverse T
3
, and inversely correlated with total T
3
and thy-
roid-stimulating hormone (TSH). In addition, PBDEs were posi-
tively related to the percentage of T
4
bound to albumin, a carrier
protein. An observed increase in thyroglobulin antibodies in men
with the highest PBDE exposures may indicate an increased suscep-
tibility to autoimmune thyroiditis among people who have been
exposed to PBDEs, according to the authors.
The findings of a positive association of PBDEs with T
4
are not
consistent with results of animal studies that have
shown decreased T
4
in rats and mice exposed to
PBDE. However, the results do align with those
of several smaller human studies. The authors
speculate the disparity may be attributable to the
fact that, while thyroid hormone regulation is
similar among vertebrates, some functions differ
by species.
A major strength of the study is the measure-
ment of the effects of PBDEs on multiple hormones
and the consideration of other environmental expo-
sures that can affect thyroid hormones. The authors
point out that their findings provide a rationale
for future mechanistic studies related to PBDE
exposure, including how those exposures may be
linked to changes in thyroid hormone metabo-
lism and binding of T
4
to serum-binding pro-
teins. Also needed, they write, are larger studies
to determine whether PBDE exposure is related
to thyroid disease in human populations.
–Richard Dahl
Environews
|
Science Selections
EPA data show that contaminant levels in fish from
Lake Michigan (above) and the other Great Lakes,
while still high, have declined consistently since 1990.
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New Pesticides, Old Problems
Despite Warnings, Use during Pregnancy Persists
The sight of scurrying cockroaches trumps warnings against using
pesticides during pregnancy. That’s one insight from a study of pes-
ticide use before and after the U.S. Environmental Protection
Agency’s 2001 and 2002 retail sales restrictions of chlorpyrifos and
diazinon [EHP 116:1681–1688; Williams et al.]. The team of U.S.
researchers also found that use of replacement pesticides is steadily
increasing to fill the void, that the air the test subjects breathed
remains surprisingly contaminated with chlorpyrifos and diazinon
up to 5 years after the restrictions went into effect, and that house-
hold use of pesticide spray cans and bug bombs contaminated the air
far more than did use of bait traps or boric acid or spraying by
professional exterminators.
In the study, 511 pregnant
inner-city women wore person-
al air samplers for a 48-hour
period during their third
trimester and reported pesticide
use and sightings of pests
throughout pregnancy. The
researchers compared their
findings from subjects enrolled
in the study between 2000 and
2001 with those from subjects
enrolled between 2002 and
2006. This reflected the timing
of the pesticide bans—retail
sales of chlorpyrifos were
phased out at the end of 2001
and diazinon at the end of
2002. Participants received
regular newsletters contain-
ing pertinent information,
including warnings about potential health effects of residential pesti-
cide use and information on alternative pest control methods.
For 6 months after chlorpyrifos went off the market, use of
replacement pesticides fell, perhaps due to elevated awareness of pesti-
cide dangers. But a steady, significant increase in sightings of cock-
roaches, the most commonly observed pest, was correlated with a
steady, significant increase in the use of replacement pesticides for
every 6-month period from 2002 through 2006. Throughout the
study period, at least 85% of the women reported using pesticides.
Chlorpyrifos and diazinon were found in more than 98% of air
samples both before and after the phase-outs, and 18–75% of the per-
sonal air samples contained at least 1 replacement pesticide. The
chemicals the researchers measured included permethrin (a commonly
used pyrethroid) and piperonyl butoxide (a pyrethroid synergist, or
chemical added to a pesticide to increase its effectiveness). The authors
say this is the first study to
document extensive residential
exposure to piperonyl butoxide.
Data on health effects of
these pyrethroid products at
the measured concentrations
are limited. However, there is
growing evidence of health and
environmental damage from
these products, which are prov-
ing to be ubiquitous both
indoors and out. The authors
say their findings indicate that
these products warrant addi-
tional research on their use,
occurrence, and health effects.
They also noted that pest resis-
tance to pyrethroids may be
playing a role in pest increases.
–Bob Weinhold
Bisphenol A Suppresses
Release of Adipose Hormone
Exposure May Contribute to Metabolic
Syndrome
Bisphenol A (BPA), a chemical used in the manufacture of
numerous consumer products, is ubiquitous throughout the envi-
ronment, and its widespread presence in human serum has been
well documented. Although animal research indicates that BPA
can alter several metabolic functions, interpretation of human
data has been more controversial. A new study now presents evi-
dence confirming that exposure of human adipose tissue and iso-
lated fat cells to environmentally relevant levels of BPA suppress-
es release of the hormone adiponectin [EHP 116:1642–1647;
Hugo et al.].
A high-calorie diet and sedentary lifestyle have both tradition-
ally been linked to metabolic syndrome—the presence of a con-
stellation of metabolic risk factors including insulin resistance,
hypertension, and elevated blood sugar and lipid levels—but
researchers are now examining environmental factors as additional
causes. Adiponectin increases insulin sensitivity and reduces tissue
inflammation, so suppression of its release could lead to insulin
resistance and increased susceptibility to metabolic syndrome, the
authors write.
The study examined three types of adipose tissue samples taken
during breast reduction, abdominoplasty, and gastric bypass
surgery. The research team incubated each type of tissue
for 6 hours in BPA or estradiol (E
2
), an endogenous human estro-
gen. They used enzyme-linked immunosorbent assay to measure
secreted adiponectin. They also used quantitative real-time poly-
merase chain reaction to compare the expression of estrogen recep-
tors and estrogen-related receptors in these tissues.
In all three tissue types, exposure to low-nanomolar concentra-
tions of BPA suppressed adiponectin as effectively or more effec-
tively compared with equimolar concentrations of E
2
. The authors
also showed that the dose response to BPA was nonmonotonic,
meaning lower doses caused different effects than higher doses.
Finally, they report for the first time similar mRNA expression lev-
els for several estrogen receptors in visceral adipose tissue, although
the role of these receptors in the suppressive nature of BPA and E
2
has yet to be determined.
The results of the data are limited by the relatively small sample
size in each tissue category, as well as the potential unknown effects
of age or obesity on tissue responsiveness. However, the authors
write that their data present clear evidence that BPA suppresses
adiponectin, potentially leading to a much higher risk of develop-
ing metabolic syndrome and its resultant adverse health effects.
They conclude that with BPA’s persistence in the environment,
more research should be done to determine the mechanism by
which the chemical suppresses adiponectin. –Tanya Tillett
Science Selections
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This and other studies have reported a strong association between
the degree of housing disrepair and both pest sightings and use of
pest control measures.
Environmental Health Perspectives • VOLUME 116
|
NUMBER 12
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December 2008 A 533