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

326 CHAPIN ET AL.
Table 85
Summary of Behavioral Studies in Rats and Mice Treated With Bisphenol A
Treatment, mg/kg
bw/day Treatment age Age at assessment Results Reference
High Utility
Rat
Treatment of dam
3.2, 32, or 320, GD 11–PND 20 6 months Lordosis behavior not affected by Kwon et al. (2000)
gavage treatment
0.1, gavage GD 3–PND 20 Open field: 8 weeks Open field: No treatment effect Negishi et al. (2004a)
Spontaneous motor Spontaneous motor activity: No
activity: 12 weeks treatment effect
Passive avoidance: 13 Passive avoidance: No treatment effect
weeks
Elevated plus maze: 14 Elevated plus maze: No treatment
weeks effect
Active avoidance: 15 Active avoidan: Fewer correct
weeks avoidance responses
Treatment of offspring
0.04, micropipette PND 23–30 45 days No treatment effect on environmental Della Seta et al. (2006)
exploration, social investigation, play,
or social interaction
k Response to novel object
k Intromission latency
Mouse
0.010, syringe GD 11–18 60 days k Conditioned place preference Laviola et al. (2005)
feeding (reinforced with amphetamine) in
females
0.010, micropipette GD 14–18 Maternal behavior of Altered maternal behaviors when Palanza et al. (2002)
(treatment of F0 F1 assessed exposure was either prenatal or as an
and F1 females) adult; however, exposure prenatally
plus as an adult was not effective
2 or 200, placed in GD 3–PND 21 5 weeks, No effect on errors in radial arm and Ryan and
back of dam’s ovariectomized Barnes mazes Vandenbergh (2006)
throat female offspring
Effects in high dose group:Puberty
advanced
k Time in open arms of plus maze
k Time in light part of light/dark
preference box
m,k Statistically significant increase, decrease compared to controls; 2 no statistically significant effects compared to controls.
estrogen sensitive in rats including prolactin regulation
in the pituitary, thymic involution, uterine pyometra, and
liver carcinogenesis to name a few. It is evident that there
are strain differences in respect to specific estrogen
induced endpoints. However, there is no clear pattern in
which one strain can be considered to be more or less
sensitive than another. The results of BPA studies with
the SD rat cannot therefore be ignored.
3.4.1 Human. There are no human data on developmental
effects of bisphenol A. A study of the
association between miscarriage and mean serum bisphenol
A levels is discussed in Section 4.4.1.
3.4.2 Experimental animal. Studies considered by
Expert Panel members to be of utility in evaluating
developmental toxicity in mice are summarized in
Tables 81, 82, 83, 84. Rat and mouse studies with
behavioral endpoints are summarized in Table 85. The
discussion of developmental toxicity is arranged according
to general endpoints evaluated.
General developmental toxicity (growth, survival,
malformations).
Rat Studies: Prenatal studies with oral dosing of rats
consistently demonstrated an absence of malformations
at doses up to 1000 mg/kg bw/day (Morrissey et al.,
1987; Kim et al., 2001b). Reduced fetal survival and body
weights at birth or during the postnatal period were
reported in studies with oral exposures occurring
throughout the entire gestation and/or lactation periods
(Tyl et al., 2000a, 2002b; Kim et al., 2001b). LOAELs for
decreased numbers of live fetuses or pups ranged from
475–1000 mg/kg bw/day (Tyl et al., 2000a, 2002b; Kim
et al., 2001b). LOAELs for decreased pup body weight at
birth were estimated at 300–1000 mg/kg bw/day (Tyl
et al., 2000a, 2002b; Kim et al., 2001b). The LOAEL for
reduced body weight during the postnatal period was
475 mg/kg bw/day (Tyl et al., 2000a, 2002b).
Mouse Studies: No increase in malformations was
observed in mice with oral gavage of bisphenol A at
doses of r1250 mg/kg bw/day (Morrissey et al., 1987).
Prenatal developmental toxicity reported for mice included
increased resorptions (LOAEL 1250 mg/kg bw/
day) and decreased fetal body weight (LOAEL 1250 mg/
kg bw/day) (Morrissey et al., 1987). Decreased body
weight during the postnatal period was also reported in
offspring of mouse dams exposed to bisphenol A during
the entire gestation and lactation period (LOAEL
Birth Defects Research (Part B) 83:157–395, 2008