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

378 CHAPIN ET AL.
Table 103
Summary of Blood LH and Testosterone Changes in Experimental Animal Studies
Endpoints/protocol LH effects a
Testosterone effects a
Reference
High Utility
Experimental animal studies
with oral exposure
Adult male and female rats 2 at 40–1000 mg/kg bw/day 2 at 40–1000 mg/kg bw/day Yamasaki et al. (2002a)
gavaged for 28 days
4-week-old male rats fed Not examined 2 at 235–950 mg/kg bw/day Takahashi and Oishi (2001,
bisphenol A in diet for 44 or or 200 mg/kg bw/day 2003)
60 days
Multiple generation gavage k in F0 adult females at 0.0002, 2 Ema et al. (2001)
dosing study in rats 0.002, and 0.020 mg/kg bw/
day but not at high dose
(0.2 mg/kg bw/day); not
considered treatmentrelated.
Experimental animal studies
with parenteral exposure
Female lambs i.m. injected at 4– 2 on blood levels during Not examined Evans et al. (2004)
11 weeks of age; ovariectomy treatment; k pulsatile
at 9 weeks of age secretion after treatment with
3.5 mg/kg bw biweekly
Limited utility
Experimental animal studies
with oral exposure
Male rats gavaged from PND k at 0.0024 mg/kg bw/day but k at 0.0024 mg/kg bw/day but Akingbemi et al. (2004)
21–35 2 at higher doses (0.010– 2 at higher doses (0.010–
200 mg/kg bw/day) 200 mg/kg bw/day)
Male rats gavaged from PND m at 0.0024 mg/kg bw/day 2 at 0.0024 mg/kg bw/day Akingbemi et al. (2004)
21–90
4-week-old mice fed bisphenol Not examined 2 at 400 mg/kg bw/day Takahashi and Oishi (2003)
A through diet for 2 months
Experimental animal studies
with parenteral exposure
4-week-old male rats s.c. dosed Not examined 2 at 200 mg/kg bw Takahashi and Oishi (2003)
on 4 days/week for 1 month
4-week-old male rats i.p. Not examined k at 20 mg/kg bw Takahashi and Oishi (2003)
injected for 1 month
a Unless otherwise stated, animals were examined immediately after the treatment period.
m,k Statistically significant increase/decrease compared to controls; 2 no statistically significant effects compared to controls.
Utility (Adequacy) for CERHR Evaluation Process: This
study suggests that fish are sensitive to bisphenol Ainduced
abnormalities in reproductive endpoints. Because
this study was conducted in fish, it is not useful in
the evaluation.
Ortiz-Zarragoitia and Cajaraville (2006), supported by
the European Commission, examined the effects of
bisphenol A exposure on the reproductive and digestive
systems of adult blue mussels. For a period of 3 weeks,
mussels were exposed to bisphenol A in acetone vehicle
at 0 or 50 ppb [lg/L] [no information on purity or
culture ware was provided]. Additional compounds
were also tested but will not be discussed. Ten mussels/
sex/group were examined at the end of the exposure
period. The digestive gland was examined for volume of
peroxisomes and peroxisomal proliferation. Gonads were
histologically evaluated and assessed for alkali-labile
phosphate level, a vitellogenin-like protein that is a
possible biomarker of endocrine disruption. Statistical
analyses included ANOVA followed by Duncan post-hoc
test, Kruskall–Wallis, and Mann–Whitney U test.
Bisphenol A had no effect on gonadal development,
gonadal alkali-labile phosphate levels, or digestive gland
peroxisomal proliferation or peroxisomal volume. However,
observations of follicular brown cell aggregates and
gonadal hemocyte infiltration in 35% of male and female
mussels indicated severe gamete resorption.
Strengths/Weaknesses: This study evaluated bisphenol
A-induced alterations in several reproductive endpoints
in adult mussels. Severe gamete resorption was
observed. Weaknesses include the failure to confirm
bisphenol A concentrations in the test water and the use
of only 1 concentration.
Utility (Adequacy) for CERHR Evaluation Process:
Because this study was conducted in the mussel, it is not
useful in the evaluation.
4.3 Utility of Reproductive Toxicity Data
4.3.1 Human. One high utility study of 42 men
occupationally exposed to bisphenol A diglycidyl ether
and 42 unexposed men evaluated the relationship
Birth Defects Research (Part B) 83:157–395, 2008