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

264 CHAPIN ET AL.
increased lordosis frequency in females in proestrus
[B11.75 vs. 3.75 times in controls]. Statistically significant
effects on sexual performance of treated males
included an increased number of intromissions [B15
compared to 11 in controls] in the postnatal exposure
group and increased duration of intromission latency
[B115 vs. 40 sec in controls] and genital sniffing [B40
vs. 16 sec in controls] in the prenatal exposure group.
The study authors stated that the results suggested a
slight intensification of sexual behavior in females,
slightly reduced performance in a limited number of
endpoints in males, but no effect on other important
sexual endpoints in males (e.g., latency of ejaculation and
refractory period). It was concluded that pre- or postnatal
exposure to bisphenol A potentiated female behavior and
depotentiated male behavior.
Strengths/Weaknesses: The work was carefully performed.
The use of a single dose level of bisphenol A is a
weakness; however, this dosing paradigm is consistent
with many other studies by this group making comparisons
between the studies relevant. Addressing aggressive/defensive
behavior as well as sexual performance
and interest in both male and female offspring is a
strength. The failure to address underlying biological
mechanisms is a weakness. Further weaknesses include
the inability to account for litter effects as the use of
multiple pups from some litters without appropriate
statistical control raises concern for possible litter effects
due to unequal litter representation
Utility (Adequacy) for CERHR Evaluation Process:
This study is inadequate for evaluation purposes due to
the inability to fully account for possible litter effects.
Dessi-Fulgheri et al. (2002), supported by the University
of Firenze, University of Siena, and MURST,
examined the effect of perinatal bisphenol A exposure on
play behavior in rats. Sprague–Dawley rats were housed
in polysulfone cages. [No information was provided in
the manuscript on chow or bedding material. The
Expert Panel has been informed that Morini MIL chow
and Lignocel bedding were used (F. Farabolli et al.,
personal communication, March 1, 2007).] Using a
pipette, rats were fed solutions containing the arachis
oil vehicle and/or bisphenol A according to 1 of 3
exposure scenarios. A control group of 9 rats was given
arachis oil from 10 days before mating until weaning of
pups on PND 21 [day of birth not defined]. Eleven rats
in the low-dose group were given 0.040 mg/kg bw/day
bisphenol A [purity not provided] from 10 days before
mating until weaning of pups. Eleven rats in the highdose
group received arachis oil vehicle from 10 days
before mating until GD 13 [day of vaginal plug not
defined], 0.400 mg/kg bw/day bisphenol A from GD
14–PND 6, and arachis oil from PND 7 until weaning.
Both doses were considered to be within the range of
human exposure. The low dose was said to represent
exposures through food occurring over a long period of
time. The high-dose was said to represent exposures
occurring through dental procedures occurring over a
short period of time. Litters were culled to 8 pups at
birth. [No information was provided in the study on the
sex distribution of the retained pups; the Expert Panel
was advised that there were 4 males and 4 females/litter
(F. Farabolli et al., personal communication, March 1,
2007).] After pups were weaned, 3 male and 3 female
pups were randomly caged together, with no siblings
co-housed in any cage. Behavioral testing was conducted
on PND 35, 45, and 55. For the behavioral testing, rats
from the same cage were individually identified by
marking them with dye. On each day of testing, the 6
cage mates were transferred to a neutral arena that was
covered in clean sawdust and video recorded for 6 min.
Behaviors recorded during the second and third minute
of each testing session were evaluated. There were 12–
15rats/sex/group. [The methods section indicates that
15 rats/sex were tested at the high-dose, 12 rats/sex at
the low dose, and 15 rats/sex in the control group.
According to Table 4 of the study, which gives the
pooled number of rats tested for 3 age periods, it
appears that 12/sex were tested in the high-dose group,
15/sex in the low-dose group, and 15/sex in the control
group. The Expert Panel has been informed that Table 4
is correct (F. Farabolli et al., personal communication,
March 1, 2007).] For statistical analyses, individual
factor scores were used as independent variables in a 3way
ANOVA that considered treatment, sex, and age.
Fisher least significant difference test was used when
appropriate. At weaning, housing conditions confounded
litter of origin that was not then accounted
for in statistical analyses.
Behavioral elements were categorized under 8 general
factors. The authors first presented results that were
pooled for the 3 different age groups. In females of the
low-dose group, bisphenol A treatment was found to
significantly increase factors addressing play directed
toward females. Factors affecting low-intensity mating
elements (e.g., crawling-under behavior) were reduced
significantly in high-dose males and females. Factors of
sociosexual exploration (e.g., genital and body sniffing)
were reduced significantly in high-dose females and in
males from both dose groups. Factors of social interest
(e.g., approaching) were reduced significantly in both
sexes at the high-dose but increased in low-dose males.
The authors next discussed results for PND 35, because it
is the approximate time period of vaginal opening in
females. Factors that were affected significantly at PND
35 included increased social interest by males and
females of the low-dose group, decreased low-intensity
mating elements by females of both dose groups, and
decreased sociosexual exploration by males of both dose
groups. The study authors concluded that 2 factors of
female behavior were masculinized by treatment: play
with females and sociosexual exploration.
Strengths/Weaknesses: A strength of this work is that
it evaluated the socio-sexual consequences of exposure,
and specifically at a young age. Weaknesses include
absence of accounting for litter influences and inadequate
statistical procedures (i.e., failure to consider the
repeated measures design). In addition, the hypothesis is
not biologically plausible (i.e., consistent with expected
effects of a chemical with an estrogenic mode of action)
and the factor analysis does not necessarily cluster the
play behaviors that are known to be sexually dimorphic.
Utility (Adequacy) for CERHR Evaluation Process:
This study is inadequate for evaluation process due to
faulty statistical procedures.
Porrini et al. (2005), supported by MURST, the
University of Firenze, and the University of Siena,
examined the effects of perinatal bisphenol A exposure
on play behavior of female rats. [No information was
provided in the manuscript about the type of feed or
Birth Defects Research (Part B) 83:157–395, 2008