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

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individuals with the SULT1A1 2 enzyme (6.3178.91 mg/
L). Adjustment for possible bisphenol A exposure
through vinyl wrap use also did not result in significant
differences between the 2 groups. The study authors
concluded that additional enzymes involved in bisphenol
A metabolism should be studied to determine
possible sensitivity differences.
One animal study demonstrated sex-related differences
in sulfation. Male versus female Sprague–Dawley
and F344 rats were found to produce higher amounts of a
bisphenol A glucuronide/sulfate conjugate (Pritchett
et al., 2002).
As noted in Table 7, one human study reported B2fold
higher blood bisphenol A concentrations in Japanese
men than women (Takeuchi and Tsutsumi, 2002). Based
on positive correlation between serum bisphenol A and
testosterone concentrations, authors speculated that sexrelated
differences in bisphenol A concentrations might
be due to androgen-related metabolism (Takeuchi and
Tsutsumi, 2002). There are no known human studies
showing inter-individual or sex-related variations in
metabolism that could lead to higher bisphenol A
concentrations in blood. Experimental animal studies
have not consistently demonstrated higher concentrations
of bisphenol A or radioactive dose in one sex
(Pottenger et al., 2000; Kurebayashi et al., 2005). In Wistar
rats orally administered 1 mg bisphenol A every 2 days
Table 60
Human Toxicokinetic Values for Total Bisphenol A Dose
Endpoint Value Reference
Oral absorption, % Z84% Völkel et al.(2002, 2005)
Dermal absorption, in vitro, % B10% European-Union (2003)
T max, min 80 Völkel et al. (2002)
Elimination half-life, hr 4–5.4 Völkel et al. (2002, 2005)
BISPHENOL A
229
for 2 or 4 weeks, liver microsomal UDPGT activity
toward 17b-estradiol and testosterone and expression of
UGT2B1 protein and mRNA were reduced in males but
not females (Shibata et al., 2002). One study reported an
B3-fold higher concentration of blood bisphenol A in
male than in female Wistar–Imamichi rats that were
apparently not treated, but there were was no sex-related
difference in percent glucuronidated bisphenol A in
serum (Takeuchi et al., 2004b). However, in an in vitro
study conducted with hepatic microsomes, glucuronidation
of bisphenol A and expression of UGT2B1 mRNA
were higher in microsomes from female than male rats.
As described in more detail in Section 2.1.2.3, one study
showed reduced capacity to glucuronidate bisphenol A
in livers from pregnant than in non-pregnant rats (Inoue
et al., 2004).
2.6 Summary of General Toxicology and Biologic
Effects
Analytical considerations. Free concentrations of
BPA measured in various matrices can be affected by
analytic techniques and methodology. Free bisphenol A
contamination from reagents and plastic ware may
contribute to the measured free concentration of bisphenol
A (Tsukioka et al., 2004; Völkel et al., 2005).
Analytical techniques employed may incorrectly overestimate
the free concentration of measured bisphenol A.
HPLC with ultraviolet, fluorescence, or electrochemical
detection is unable to make definitive identification of
bisphenol A or bisphenol A glucuronides, because
similar retention times may occur for the metabolites of
other endogenous and exogenous compounds (Völkel
et al., 2005). Bisphenol A glucuronide can also be
hydrolyzed and in some cases degraded to unknown
components either in acidic or basic pH solutions of
diluted urine, adding another potential source of error in
the measurement of sample levels of bisphenol A and its
Table 61
Concentrations of Bisphenol A in Maternal and Fetal Samples a
Bisphenol A concentrations, mg/L, median (range) or mean7SD
Serum or plasma
Study description; analytical
method Maternal Fetal
Other fetal
compartments Reference
21 samples collected in women in 0.5 (Non-detectable
the U.S. before 20 weeks o0.5–1.96) 10% of
gestation; LC with amniotic fluid
electrochemical detection samples detectable
37 German women, 32–41 weeks 3.1 (0.3–18.9); 4.473.9 2.3 (0.2–9.2); 2.972.5 12.7 (ng/g) (1.0–104.9)
gestation; GC/MS 11.279.1) Placental
tissue
9 sets of maternal and umbilical 0.43 (0.21–0.79) 0.64 (0.45–0.76)
cord blood samples obtained at 0.4670.2 0.6270.13
birth in Japanese patients;
HPLC
180 Malaysian newborns; GC/MS Non-detectable
(o0.05) to 4.05 88%
of samples
detectable
Engel et al. (2006)
Schönfelder et al.
(2002b)
Kuroda et al. (2003)
Tan and Mohd (2003)
a As discussed in Section 1.1.5, ELISA may overestimate bisphenol A concentrations so only results from studies based on HPLC, GC/
MS, and LC/MS are presented.
Birth Defects Research (Part B) 83:157–395, 2008