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

postnatal rearing. Pups were weaned on PND 23 (day of
birth not defined). On PND 10 and 23, 4–7 rats/group
[10–11/group according to figures in the study] were
killed and their brains were removed to examine effects
on sst2 receptors in the limbic region. Receptor binding
was assessed using 125 I-Tyr 0 -somatostatin-14 as a ligand.
At the same ages, interactions of sst2 with a-containing gaminobutyric
acid (GABA) receptors, using the agonists
zolpidem and Ro 15-4513, were examined in 12–13 rats/
group. Results were reported for only the high-dose of
bisphenol A (0.400 mg/kg bw/day) because higher
affinity was obtained for receptor ligand binding.
Statistical analyses included Student t-test, ANOVA,
and Newman–Keuls multiple range test. Analyses did
not account for litter of origin.
Strengths/Weaknesses: Strengths of this study are the
fact that it appears to have been carefully performed and
used biologically-relevant concentrations delivered orally.
A weakness is the purposeful confounding of litter
of origin through cross-fostering
Utility (Adequacy) for CERHR Evaluation Process:
This study is inadequate due to experimental design that
did not sufficiently account for litter effects.
Facciollo et al. (2005), supported by the Italian
Ministry of University Education and Research, examined
the effects of bisphenol A on expression of
somatostatin subtype 3 (sst 3) receptor mRNA in brains
of female rats exposed during development and investigated
whether the aGABAA receptor is also involved in
this effect. Sprague–Dawley rats were housed in stainless
steel cages. [No information was provided about the
type of feed or bedding used.] Beginning 8 days before
mating and continuing through the mating period (5 or 8
days) and during pregnancy and lactation (42 days), 8
rats received the arachis oil vehicle and 12 rats/group
received bisphenol A [purity not reported] at 0.040 or
0.400 mg/kg bw/day. Vehicle or bisphenol A were orally
administered by pipette. To minimize litter effects, 1
female pup from each litter was fostered to a dam from
the same treatment group (8 pups/dam). Pups were
weaned on PND 23. On PND 7 and at 55 days of age, 4
rats/group/time period were killed. Brains were sectioned
and a 32 S-labeled probe was used in an in situ
hybridization method to measure sst3 mRNA expression.
The effects of aGABAA receptor subunits on expression
of sst3 mRNA was examined by incubating the brain
sections in 1 nM–100 mM of aGABAA receptor agonists
(zolpidem, flunitrazepam, RY 080, and RO 15-4513).
Additional brain sections from high-dose rats were used
to determine interactions between sst 3 with a 1 and a 5
subunits with or without addition of 5–500 nM zolpidem
or RY 080. Statistical analyses included ANOVA followed
by Dunnett t-test or Neuman–Keuls multiple range posthoc
test, when analysis by ANOVA indicated statistical
significance.
Changes in sst3 expression varied with dose and age.
Expression patterns were changed in the presence of
aGABA A receptor agonists. Based on their findings, the
study authors concluded that bisphenol A exposure can
affect cross-talking mechanisms involved in the plasticity
of neural circuits with resulting influences on neuroendocrine/sociosexual
behaviors.
Strengths/Weaknesses: Strengths of this study are the
fact that it appears to have been carefully performed and
used biologically-relevant concentrations. A weakness is
Birth Defects Research (Part B) 83:157–395, 2008
BISPHENOL A
261
the purposeful confounding of litter of origin through
cross-fostering.
Utility (Adequacy) for CERHR Evaluation
Process: This study is inadequate due to experimental
design.
Aloisi et al. (2002), supported in part by the Italian
Ministry for Universities and Scientific and Technological
Research (MURST), examined the effects of prenatal
or postnatal bisphenol A exposure on the pain response
of rats. [No information was provided in the manuscript
on chow or composition of caging and bedding.
The Expert Panel has been informed that Harlan Teklad
2018 feed, Lignocel bedding, and polysulfone cages
were used (F. Farabollini et al., personal communication,
March 1, 2007).] Sprague–Dawley rats were fed
peanut oil vehicle (n 5 13) or 0.040 mg/kg bw/day
bisphenol A [purity not given in the manuscript;
Z95% according to the authors (F. Farabollini et al.,
personal communication, March 1, 2007)] (n 5 7/group)
by pipette during pregnancy and lactation. Within 48 hr
after birth, the offspring were sexed and cross-fostered to
form the following groups:
* Prenatal exposure group—born to dams receiving
bisphenol A and nursed by dams receiving the peanut
oil vehicle (n 5 11 males; 9 females);
* Postnatal exposure group—born to vehicle control
dams but fostered to bisphenol A treated dams (n 5 11
males; 9 females); and
* Vehicle control group—born to and nursed by dams
exposed to the vehicle control (n 5 16 males and 11
females).
At 22 weeks of age, the rats were randomly assigned to
sham or formalin treatment groups, but the sham group
was not analyzed. The formalin group was s.c. injected
with 10% formalin on the dorsal surface of the right hind
paw. Pain behaviors, such as licking, flexing, and jerking
of the paw were recorded for 60 min. Following testing,
the phase of the estrous cycle was determined and blood
was drawn to measure plasma levels of testosterone in
males and corticosterone and 17b-estradiol in both sexes
by RIA. Data were analyzed by ANOVA followed by
post-hoc least significant difference test.
The frequency of paw jerking was decreased at 30–
60 min following formalin injection in postnatally exposed
rats. [The study abstract and results section
indicate that the effect occurred in males and females,
but according to data presented in figures of the study,
the effect only appeared to have occurred in males.]
Duration of flexion was increased 0–30 min following
formalin injection in both sexes exposed prenatally to
bisphenol A. Although statistical significance was not
attained, the study authors noted an increase in licking
duration at 0–30 min following formalin injection in
females exposed to bisphenol A during prenatal development.
No effects were observed on open-field behaviors
or plasma levels of testosterone, 17b-estradiol, or
corticosterone. The study authors concluded that their
findings indicated sex- and exposure-related modifications
of neural pathway activity or nociception centers
following exposure to bisphenol A.
Strengths/Weaknesses: A strength of this study is the
added dimension being investigated (pain response). A
weaknesses, however, are use of a single dose and the