Monograph on the Potential Human Reproductive and ... - OEHHA

184 CHAPIN ET AL.
fetuses (3.572.7 vs. 1.771.5 ng/mL, P 5 0.016). Bisphenol
A concentrations were measured in placenta samples
at 1.0–104.9 mg/kg.
Ikezuki et al. (2002) measured concentrations of
bisphenol A in serum from 30 healthy premenopausal
women, 37 women in early pregnancy, 37 women in late
pregnancy, and 32 umbilical cord blood samples. Concentrations
of bisphenol A were also measured in 32
samples of amniotic fluid obtained during weeks 15–18
of gestation, 38 samples of amniotic fluid obtained at fullterm
cesarean section, and 36 samples of ovarian
follicular fluid collected during in vitro fertilization
procedures. [It was not stated if different sample types
were obtained from the same subjects.] An ELISA
method was used to measure bisphenol A concentrations
and results were verified by HPLC. The mean7SD
concentration of bisphenol A in follicular fluid was
reported at 2.470.8 mg/L. As summarized in Table 7 for
nonpregnant women and Table 9 for maternal and fetal
samples, concentrations of bisphenol A in follicular fluid
were similar to those detected in the serum of fetuses
and pregnant and non-pregnant women and in amniotic
fluid collected in late pregnancy (B1–2 mg/L). Bisphenol
A concentrations in amniotic fluid samples collected in
early pregnancy were B5-fold higher than in other
samples, and the difference achieved statistical significance
(Po0.0001). Study authors postulated that the
higher concentrations of bisphenol A in amniotic fluid
collected during gestation weeks 15–18 may have
resulted from immature fetal liver function. They noted
that according to unpublished data from their laboratory,
the percentage of glucuronidated bisphenol A in midterm
amniotic fluid was B34%, which is much lower
than reported values for other human fluids (490%).
Yamada et al. (2002) measured bisphenol A concentrations
in maternal serum and amniotic fluid from
Japanese women. Samples were collected between
1989–1998 in women undergoing amniocentesis around
gestation week 16. One group of samples was obtained
from 200 women carrying fetuses with normal karyotypes,
and a second group of samples was obtained from
48 women carrying fetuses with abnormal karyotypes.
An ELISA method was used to measure bisphenol A
concentrations. [As discussed in Section 1.1.5, ELISA
may overestimate bisphenol A.] Concentrations of
bisphenol A measured in maternal plasma and amniotic
fluid are summarized in Table 9. Median concentrations
of bisphenol A in maternal serum (B2–3 mg/L) were
significantly higher [B10-fold] than concentrations in
amniotic fluid (B0–0.26 mg/L) in the groups carrying
fetuses with normal and abnormal karyotypes. However,
in 8 samples from women carrying fetuses with normal
karyotypes, high concentrations (2.80–5.62 mg/L) of
bisphenol A were measured in amniotic fluid. The
study authors interpreted the data as indicating that
bisphenol A does not accumulate in amniotic fluid in
most cases but accumulation is possible in some
individuals. Bisphenol A concentrations in maternal
blood were significantly higher [by B33%] in woman
carrying fetuses with abnormal versus normal karyotypes.
However, the study authors noted that the
effect may not be related to bisphenol A exposure
because there was no adjustment for maternal age, and
concentrations in amniotic fluid did not differ between
groups. In the group carrying fetuses with normal
karyotypes, data obtained from 1989–1998 were summarized
by year. Median bisphenol A concentrations in
serum significantly decreased over that time from a
concentration of 5.62 mg/L detected in 1989 to 0.99 mg/L
in 1998.
Kuroda et al. (2003) used an HPLC method to measure
bisphenol A concentrations in 9 sets of maternal and cord
blood samples obtained from Japanese patients at the
time of delivery. Bisphenol A concentrations were also
measured in 21 sets of serum and ascitic fluid samples
collected from sterile Japanese patients of unspecified
sexes and ages. Results for pregnant women are
summarized in Table 9. Mean7SD concentrations of
bisphenol A were lower in maternal (0.4670.20 ppb [lg/
L]) than cord blood (0.6270.13 ppb [lg/L]). There was a
weak positive correlation (r 5 0.626) between bisphenol
A concentrations in maternal and cord blood. Concentrations
of bisphenol A in the blood of sterile patients are
summarized Table 7. There were no differences between
pregnant and non-pregnant blood levels (Kuroda et al.,
2003). Mean7SD concentrations of bisphenol A were
higher in ascitic fluid (0.5670.19 ppb [lg/L]) than in
serum (0.4670.20 ppb [lg/L]). The correlation between
bisphenol A concentration in serum and ascitic fluid was
relatively strong (r 5 0.785).
Tan and Mohd (2003) used a GC/MS method to
measure bisphenol A concentrations in cord blood at
delivery in 180 patients at a Malaysian medical center.
Bisphenol A was detected in 88% of samples. As noted in
Table 9 concentrations ranged from o0.10–4.05 mg/L.
Calafat et al. (2006) reported a median bisphenol A
concentration of B1.4 mg/L [as estimated from a graph]
in milk from 32 women. Bisphenol A was measured after
enzymatic hydrolysis of conjugates. Ye et al. (2006) found
measurable milk concentrations of bisphenol A in
samples from 18 of 20 lactating women. Free bisphenol
A was found in samples from 12 women. The median
total bisphenol concentration in milk was 1.1 mg/L
(range: undetectable to 7.3 mg/L). The median free
bisphenol A concentration was 0.4 mg/L (range: undetectable
to 6.3 mg/L).
Sun et al. (2004) used an HPLC method to measure
bisphenol A concentrations in milk from 23 healthy
lactating Japanese women. Bisphenol A concentrations
ranged from 0.28–0.97 mg/L, and the mean7SD concentration
was reported at 0.6170.20 mg/L. No correlations
were observed between bisphenol A and triglyceride
concentrations in milk. Values from six milk samples
were compared to maternal and umbilical blood samples
previously reported in a study by Kuroda et al. (2003).
Bisphenol A values were higher in milk, and the milk/
serum ratio was reported at 1.3. Bisphenol A values in
milk were comparable to those in umbilical cord serum.
[It was not clear whether milk and serum samples were
obtained from the same volunteers in the two studies.]
Schaefer et al. (2000) measured concentrations of
bisphenol A and other compounds in uterine endometrium
of women undergoing hysterectomy for uterine
myoma at a German medical center. Endometrial and fat
samples were obtained between 1995–1998 from 23
women (34–51 years old) with no occupational exposure.
Samples were handled with plastic-free materials and
stored in glass containers. Concentrations of environmental
chemicals were measured in samples by GC/MS.
None of 21 fat samples had detectable concentrations of
Birth Defects Research (Part B) 83:157–395, 2008