Bisphenol Aggression
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Page 1
Bisphenol Aggression
Environews Science Selections
Size in the City
New York Pollution May
Lower Birth Weight
Current levels of environmental
pollutants in New York City can
adversely affect fetal development,
according to a new study by a
team led by Frederica Perera of
Columbia University’s Center for
Children’s Environmental Health
[EHP 111:201–205]. The study
found a significant link between
prenatal exposure to common
environmental pollutants—
including the combustion by-
products polycyclic aromatic
hydrocarbons (PAHs) and the
once widely used organophos-
phate pesticide chlorpyrifos—and
reduced birth weight and head
circumference in two inner-city
minority populations. (In recent
years, the U.S. Environmental
Protection Agency has regulated
chlorpyrifos, and residential uses are being phased out.)
The researchers monitored more than 260 black and Domin-
ican women during their pregnancies and collected biological sam-
ples from each mother and baby at delivery. During pregnancy,
the mothers wore personal air monitors to gauge their exposure to
eight airborne carcinogenic PAHs. The team used plasma levels of
chlorpyrifos to estimate exposure to this pesticide and plasma levels
of cotinine to estimate environmental tobacco smoke exposure (all
of the mothers were nonsmokers). The team’s approach combined
use of biomarkers with epidemiologic methods. This is the first
study to use prenatal personal air monitoring and biomarkers to
assess the effects of these particular prenatal exposures on birth
outcomes.
The team found that median exposure to chlorpyrifos during
pregnancy was associated with a 4% decrease in birth weight and
a 2% decrease in birth length in the overall cohort. They also
found that median exposure to PAHs during pregnancy was asso-
ciated with a 9% reduction in birth weight and a 2% reduction in
head circumference in black newborns. No significant reductions
were noted in Dominicans. In addition, the study linked prenatal
exposure to chlorpyrifos with decreased birth weight and birth
length in both black and Dominican infants. The mechanism for
these agents’ observed effects on fetal growth and development is
not known. There was no significant effect correlated with envi-
ronmental tobacco smoke, possibly because all the mothers are
themselves nonsmokers.
In previous studies of mothers and newborns in Krakow,
Poland, the researchers had found associations between these same
birth outcomes and PAH exposure. However, the Polish popula-
tion was exposed to 46% higher concentrations of PAHs than the
present New York City cohort due to air pollution from coal burn-
ing. The fact that the New York City effects were seen at lower
concentrations is of concern, according to Perera, because several
studies have reported that reduction in head circumference at birth
or during the first year of life correlates with lower IQ and poorer
cognitive functioning and school performance in childhood.
The lack of an association between PAH exposure and
adverse effects in the Dominican newborns may be due to
unmeasured differences in exposure and susceptibility, the
researchers speculate. The fact that birth outcomes such as
weight, head circumference, and age of fetus at delivery were
overall less favorable and more variable in blacks compared to
Dominicans could also explain the difference. The authors are
evaluating whether genetic and other susceptibility factors influ-
ence risk from these exposures. –Julie Wakefield
Bisphenol Aggression
Effects Shown in Mice
Although many studies have documented the adverse effects of
endocrine disruptors on reproductive organs, until recently little
research has been done on the influence of these chemicals on
behavioral development. A new study led by Keisuke Kawai of
Kyushu University evaluates the effect of fetal exposure to the
estrogen mimic bisphenol A on aggression and serum testosterone
concentrations in male mice [EHP 111:175–178]. Bisphenol A is
a monomer used to manufacture polycarbonate plastic and the
resin used to line food and drink cans. It also is a component of
the plastic used in dental fillings. The Japanese team found that
bisphenol A, administered to pregnant mice during the early peri-
od of gestation, temporarily exaggerated aggressive behavior in
male offspring. Low-dose bisphenol A also interfered with the nor-
mal development of the offspring’s reproductive organs.
From gestation days 11 to 17, pregnant CD-1 mice were fed
bisphenol A at doses of either 2 ng/g or 20 ng/g body weight. Their
male offspring underwent aggression rating and blood sampling for
testosterone at 8, 12, and 16 weeks of age. (Mice are considered to
have just reached sexual maturity at age 8 weeks.) The team rated
aggression according to how a male mouse acted toward an age-
matched control “opponent” introduced into its cage. The scientists
assessed the amount of time each test mouse spent sniffing or
attacking its opponent over a 7-minute period.
At 8 weeks, males whose mothers were exposed to either
concentration of bisphenol A were rated as significantly more
aggressive than the control group, and the increase in aggression C
o
r
b
i
s
A 110 VOLUME 111 | NUMBER 2 | February 2003 • Environmental Health Perspectives
Little pollution causes big problems. Even relatively low pollution exposures can result in smaller babies.
Size in the City
New York Pollution May
Lower Birth Weight
Current levels of environmental
pollutants in New York City can
adversely affect fetal development,
according to a new study by a
team led by Frederica Perera of
Columbia University’s Center for
Children’s Environmental Health
[EHP 111:201–205]. The study
found a significant link between
prenatal exposure to common
environmental pollutants—
including the combustion by-
products polycyclic aromatic
hydrocarbons (PAHs) and the
once widely used organophos-
phate pesticide chlorpyrifos—and
reduced birth weight and head
circumference in two inner-city
minority populations. (In recent
years, the U.S. Environmental
Protection Agency has regulated
chlorpyrifos, and residential uses are being phased out.)
The researchers monitored more than 260 black and Domin-
ican women during their pregnancies and collected biological sam-
ples from each mother and baby at delivery. During pregnancy,
the mothers wore personal air monitors to gauge their exposure to
eight airborne carcinogenic PAHs. The team used plasma levels of
chlorpyrifos to estimate exposure to this pesticide and plasma levels
of cotinine to estimate environmental tobacco smoke exposure (all
of the mothers were nonsmokers). The team’s approach combined
use of biomarkers with epidemiologic methods. This is the first
study to use prenatal personal air monitoring and biomarkers to
assess the effects of these particular prenatal exposures on birth
outcomes.
The team found that median exposure to chlorpyrifos during
pregnancy was associated with a 4% decrease in birth weight and
a 2% decrease in birth length in the overall cohort. They also
found that median exposure to PAHs during pregnancy was asso-
ciated with a 9% reduction in birth weight and a 2% reduction in
head circumference in black newborns. No significant reductions
were noted in Dominicans. In addition, the study linked prenatal
exposure to chlorpyrifos with decreased birth weight and birth
length in both black and Dominican infants. The mechanism for
these agents’ observed effects on fetal growth and development is
not known. There was no significant effect correlated with envi-
ronmental tobacco smoke, possibly because all the mothers are
themselves nonsmokers.
In previous studies of mothers and newborns in Krakow,
Poland, the researchers had found associations between these same
birth outcomes and PAH exposure. However, the Polish popula-
tion was exposed to 46% higher concentrations of PAHs than the
present New York City cohort due to air pollution from coal burn-
ing. The fact that the New York City effects were seen at lower
concentrations is of concern, according to Perera, because several
studies have reported that reduction in head circumference at birth
or during the first year of life correlates with lower IQ and poorer
cognitive functioning and school performance in childhood.
The lack of an association between PAH exposure and
adverse effects in the Dominican newborns may be due to
unmeasured differences in exposure and susceptibility, the
researchers speculate. The fact that birth outcomes such as
weight, head circumference, and age of fetus at delivery were
overall less favorable and more variable in blacks compared to
Dominicans could also explain the difference. The authors are
evaluating whether genetic and other susceptibility factors influ-
ence risk from these exposures. –Julie Wakefield
Bisphenol Aggression
Effects Shown in Mice
Although many studies have documented the adverse effects of
endocrine disruptors on reproductive organs, until recently little
research has been done on the influence of these chemicals on
behavioral development. A new study led by Keisuke Kawai of
Kyushu University evaluates the effect of fetal exposure to the
estrogen mimic bisphenol A on aggression and serum testosterone
concentrations in male mice [EHP 111:175–178]. Bisphenol A is
a monomer used to manufacture polycarbonate plastic and the
resin used to line food and drink cans. It also is a component of
the plastic used in dental fillings. The Japanese team found that
bisphenol A, administered to pregnant mice during the early peri-
od of gestation, temporarily exaggerated aggressive behavior in
male offspring. Low-dose bisphenol A also interfered with the nor-
mal development of the offspring’s reproductive organs.
From gestation days 11 to 17, pregnant CD-1 mice were fed
bisphenol A at doses of either 2 ng/g or 20 ng/g body weight. Their
male offspring underwent aggression rating and blood sampling for
testosterone at 8, 12, and 16 weeks of age. (Mice are considered to
have just reached sexual maturity at age 8 weeks.) The team rated
aggression according to how a male mouse acted toward an age-
matched control “opponent” introduced into its cage. The scientists
assessed the amount of time each test mouse spent sniffing or
attacking its opponent over a 7-minute period.
At 8 weeks, males whose mothers were exposed to either
concentration of bisphenol A were rated as significantly more
aggressive than the control group, and the increase in aggression C
o
r
b
i
s
A 110 VOLUME 111 | NUMBER 2 | February 2003 • Environmental Health Perspectives
Little pollution causes big problems. Even relatively low pollution exposures can result in smaller babies.
Page 2
Science Selections
Environmental Health Perspectives • VOLUME 111 | NUMBER 2 | February 2003 A 111
was comparable in both dose groups. At 12 and 16 weeks, however,
no difference was found between the treated and control mice.
For the low-dose mice, the relative testis weight per gram of
body weight at 8 and 12 weeks was significantly lower than that of
the controls. The same effect was noted for the high-dose mice at
12 weeks only. Both dose groups had normal testis weight at 16
weeks. Testosterone concentration was never significantly different
in treated mice compared to the controls.
Whether bisphenol A also affected reproductive organ function
is unclear. However, neither relative testis weight nor testosterone
concentration appeared to be related to aggressive behavior.
Perhaps more interesting is the observation that the low dose of
bisphenol A seemed to have a greater effect than the higher dose on
relative testis weight. Some researchers have suggested that indeed, low
doses of endocrine disruptors might cause unique outcomes that will
not be observed at higher doses. The mechanisms of the low-dose
effects of endocrine disruptors such as bisphenol A remain unclear,
and their pathway has yet to be determined. –Julian Josephson
Life near the Fast Lane
An Increased Risk of Birth Problems
Several recent epidemiologic studies have suggested that exposure
during pregnancy to ambient air pollution—including compounds
released in motor vehicle exhaust—can increase the risk of preterm
birth and low birth weight. Now, investigations
are beginning to examine the question of whether
pregnant women residing close to heavily traveled
roadways have a greater occurrence of these
adverse birth outcomes. In this month’s issue,
Michelle Wilhelm and Beate Ritz of the School of
Public Health at the University of California, Los
Angeles, report that such women do indeed face
greater risk of adverse birth outcomes, especially if
their third trimester falls during the autumn or
winter months [EHP 111:207–216].
The epidemiologic case–control study involved
nearly 51,000 infants born between 1994 and
1996 in 112 of the 269 zip code areas in Los
Angeles County, California. These particular areas
were selected because they are intersected by free-
ways and major arteries carrying more automobile
traffic—and thus experiencing more traffic-related
air pollution—than less-traveled roads. The cases
included preterm infants and term low birth
weight infants. The controls included term normal
birth weight infants born in the same year and the
same set of zip code areas.
The researchers mapped home locations for
each of the cases and controls, and calculated a
distance-weighted traffic density (DWTD) value
for each subject as a measure of exposure to traf-
fic-related air pollution. This measure accounts for
residential proximity to roadways surrounding
homes and the level of traffic on those roadways,
and assumes that 96% of all motor vehicle exhaust
pollutants disperse at 500 feet from the roadway.
They also obtained ambient air pollution moni-
toring data compiled by the South Coast Air
Quality Management District to assess the impact
of background air pollution separately from that
of traffic-related pollution. Using these covariants,
Wilhelm and Ritz were able to calculate risk and
odds ratios to assess the influence of roadway proximity on adverse
birth outcomes.
They observed an approximately 10–20% increase in the risk
of preterm birth (both normal and low birth weight infants) and
the risk of term low birth weight in infants born to women living
close to heavily traveled roadways. This was after controlling for
measures of socioeconomic status and several other known risk
factors for low birth weight and preterm birth, such as maternal
age, race, and prenatal care.
The researchers found higher risks for women whose third
trimester fell during the autumn and winter months. Women
whose third trimester fell during the fall/winter months and who
were in the highest DWTD quintile had an estimated 39%
greater risk of giving birth to a term low birth weight infant and a
24% greater risk of having a preterm low birth weight infant,
compared to women in the lowest DWTD quintile. No effect was
found for women with spring/summer third trimesters at any
DWTD level.
The researchers say these findings correlate with more stagnant
air conditions present in the winter months in the Los Angeles
basin. Given the weather conditions at that time of year, it is
expected that pollution levels will be higher, and thus it also would
be expected that women in their third trimester living close to the
roadways experienced increased risk, due to the increased exposure.
The biological mechanisms whereby air pollution may cause
adverse birth outcomes remain to be determined. –Ernie Hood
P
o
w
e
r
P
h
o
t
o
s
Clogged arteries bad for babies. Make that traffic arteries—mothers living close to
heavily traveled highways may be at greater risk for having preterm or low birth weight
babies.
Environmental Health Perspectives • VOLUME 111 | NUMBER 2 | February 2003 A 111
was comparable in both dose groups. At 12 and 16 weeks, however,
no difference was found between the treated and control mice.
For the low-dose mice, the relative testis weight per gram of
body weight at 8 and 12 weeks was significantly lower than that of
the controls. The same effect was noted for the high-dose mice at
12 weeks only. Both dose groups had normal testis weight at 16
weeks. Testosterone concentration was never significantly different
in treated mice compared to the controls.
Whether bisphenol A also affected reproductive organ function
is unclear. However, neither relative testis weight nor testosterone
concentration appeared to be related to aggressive behavior.
Perhaps more interesting is the observation that the low dose of
bisphenol A seemed to have a greater effect than the higher dose on
relative testis weight. Some researchers have suggested that indeed, low
doses of endocrine disruptors might cause unique outcomes that will
not be observed at higher doses. The mechanisms of the low-dose
effects of endocrine disruptors such as bisphenol A remain unclear,
and their pathway has yet to be determined. –Julian Josephson
Life near the Fast Lane
An Increased Risk of Birth Problems
Several recent epidemiologic studies have suggested that exposure
during pregnancy to ambient air pollution—including compounds
released in motor vehicle exhaust—can increase the risk of preterm
birth and low birth weight. Now, investigations
are beginning to examine the question of whether
pregnant women residing close to heavily traveled
roadways have a greater occurrence of these
adverse birth outcomes. In this month’s issue,
Michelle Wilhelm and Beate Ritz of the School of
Public Health at the University of California, Los
Angeles, report that such women do indeed face
greater risk of adverse birth outcomes, especially if
their third trimester falls during the autumn or
winter months [EHP 111:207–216].
The epidemiologic case–control study involved
nearly 51,000 infants born between 1994 and
1996 in 112 of the 269 zip code areas in Los
Angeles County, California. These particular areas
were selected because they are intersected by free-
ways and major arteries carrying more automobile
traffic—and thus experiencing more traffic-related
air pollution—than less-traveled roads. The cases
included preterm infants and term low birth
weight infants. The controls included term normal
birth weight infants born in the same year and the
same set of zip code areas.
The researchers mapped home locations for
each of the cases and controls, and calculated a
distance-weighted traffic density (DWTD) value
for each subject as a measure of exposure to traf-
fic-related air pollution. This measure accounts for
residential proximity to roadways surrounding
homes and the level of traffic on those roadways,
and assumes that 96% of all motor vehicle exhaust
pollutants disperse at 500 feet from the roadway.
They also obtained ambient air pollution moni-
toring data compiled by the South Coast Air
Quality Management District to assess the impact
of background air pollution separately from that
of traffic-related pollution. Using these covariants,
Wilhelm and Ritz were able to calculate risk and
odds ratios to assess the influence of roadway proximity on adverse
birth outcomes.
They observed an approximately 10–20% increase in the risk
of preterm birth (both normal and low birth weight infants) and
the risk of term low birth weight in infants born to women living
close to heavily traveled roadways. This was after controlling for
measures of socioeconomic status and several other known risk
factors for low birth weight and preterm birth, such as maternal
age, race, and prenatal care.
The researchers found higher risks for women whose third
trimester fell during the autumn and winter months. Women
whose third trimester fell during the fall/winter months and who
were in the highest DWTD quintile had an estimated 39%
greater risk of giving birth to a term low birth weight infant and a
24% greater risk of having a preterm low birth weight infant,
compared to women in the lowest DWTD quintile. No effect was
found for women with spring/summer third trimesters at any
DWTD level.
The researchers say these findings correlate with more stagnant
air conditions present in the winter months in the Los Angeles
basin. Given the weather conditions at that time of year, it is
expected that pollution levels will be higher, and thus it also would
be expected that women in their third trimester living close to the
roadways experienced increased risk, due to the increased exposure.
The biological mechanisms whereby air pollution may cause
adverse birth outcomes remain to be determined. –Ernie Hood
P
o
w
e
r
P
h
o
t
o
s
Clogged arteries bad for babies. Make that traffic arteries—mothers living close to
heavily traveled highways may be at greater risk for having preterm or low birth weight
babies.
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