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

172 CHAPIN ET AL.
the blood of male than female fetuses (3.572.7 vs.
1.771.5 ng/mL, P 5 0.016). Bisphenol A concentrations
were measured in placental 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 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 They noted that according to unpublished data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 mid-term 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
and 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 that 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 andcordblood.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])thaninserum
(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.
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
to bisphenol A. 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 bisphenol A. Bisphenol A was detected
in 1 of 23 endometrial samples; the median concentration
was reported at o1 mg/kg wet weight, and the range was
reported at 0–13 mg/kg. [It is not known why a median
value and range were reported when bisphenol A was
only detected in 1 sample.]
As part of a study to compare an ELISA and an LC/MS
method for biological monitoring of bisphenol A, Inoue
et al. (2002) measured concentrations of bisphenol A in
semen samples obtained from 41 healthy Japanese
volunteers (18–38 years old). Analysis by the ELISA
method indicated bisphenol A concentrations ranging
from concentrations below the detection limit (2.0 mg/L)
to 12.0 mg/L. The LC/MS method indicated that the
bisphenol A concentration in all samples was o0.5 mg/L,
the LOQ. The study authors concluded that the LC/MS
method was more accurate and sensitive and that the
ELISA method overestimated bisphenol A concentrations,
possibly due in part to nonspecific antibody
interactions.
1.2.4 Human exposure
1.2.4.1 General population exposure
1.2.4.1.1 Estimates based on bisphenol A concentrations in
food or environment: Wilson et al. (2003) estimated
aggregate exposures to bisphenol A in preschool aged
children (2–5 years) from the U.S. In 1997, numerous
chemicals were surveyed, but only bisphenol A results
are reported here. Ten child care centers were surveyed
Birth Defects Research (Part B) 83:157–395, 2008