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

Endpoint
BISPHENOL A 363
Table 95
Effects Observed in Adult Mice Dosed With Bisphenol A in a Continuous Breeding Study a
Dose, % in diet [mg/kg bw/day]
0.25 [437.5] 0.5 [875] 1.0 [1750] BMD10 BMDL10 BMD1SD BMDL1SD
F0 males and females
Litters/pair 2 k 5% k 9% 1.0 [1750] 0.74 [1295] 0.96 [1680] 0.66 [1155]
Postpartum dam weight b
2 2 k 6–9% 1.0 [1750] 0.83 [1452] 0.87 [1522] 0.66 [1155]
Necropsy dam weight No data No data k 4%
Percent motile sperm
Relative organ weight, males
No data No data k39%
c
Liver No data No data m 29%
Kidney/adrenal No data No data m 16%
Seminal vesicle
Relative organ weight, females
No data No data k 19%
c
Liver No data No data m 27%
Kidney/adrenal No data No data m 10%
Liver lesions, males and females d
No data No data m e
Kidney lesions, males and females d No data No data m e
F1 males and females
Relative organ weight, males c
Liver m 7% m 7% m 29% 0.62 [1085] 0.42 [735] 0.59 [1032] 0.39 [682]
Kidney/adrenal f
m 16% m 20% m 20% 0.18 [315] 0.14 [245] 0.15 [262] 0.12 [210]
Left testis/epididymis f
2 k 10% k 9% 0.64 [1120] 0.32 [560] 0.53 [928] 0.27 [472]
Right testis g
2 k 13% 2
Right epididymis f
k 11% k 16% k 18% 0.24 [420] 0.15 [262] 0.46 [805] 0.25 [438]
Seminal vesicle
Relative organ weight, females
k 11% 2 k 28% 0.40 [700] 0.29 [508] 0.66 [1155] 0.47 [822]
c
Liver m 6% m 13% m 20% 0.49 [858] 0.38 [665] 0.45 [788] 0.35 [612]
Kidney/adrenal g
m 13% m 15% m 13%
Percent motile sperm g
2 k 31% 2
Liver lesions, males d
m e
m e
m e
Liver lesions, females d
2 m e
m e
Kidney lesions, males and females m e
m e
m e
a
NTP (1985a).
b
Values were reported following the birth of 5 litters, the benchmark doses are for values reported following the birth of the fifth litter
because the greatest magnitude of effect was observed at that time point.
c
Relative organ weights were adjusted for body weight; when absolute and relative organ weights changed in the same direction, only
the relative organ weights were listed in this table.
d
See text for a description of the types of lesions observed.
e
It does not appear that statistical analyses were conducted for histopathology data, but incidence was increased compared to controls.
f
Benchmark doses were estimated using a polynomial model.
g
Benchmark doses were not estimated for endpoints without dose-response relationships.
m,k Statistically significant increase, decrease compared to controls; 2 no statistically significant effects compared to controls.
Table 96
Effects in Immature F1 Mice in a Continuous Breeding Study With Bisphenol A
Dose, % in diet [mg/kg bw/day]
Endpoint 0.25 [437.5] 0.5 [875] 1.0 [1750] BMD 10 BMDL 10 BMD 1SD BMDL 1SD
Live pups/litter
Proportion pups born alive
Live birth weight b
Mortality by PND 21 c
2
2
2
2
k 20%
2
m5%
2
k 48%
k 4%
m 6%
m to 37.5%
0.30 [525]
3.0 [5250]
0.43 [752]
0.48 [840]
0.20 [350]
0.79 [1382]
0.40 [700]
0.43 [752]
0.34 [595]
a NTP (1985a).
b Hill model used for benchmark dose calculations.
c Control mortality was 6.3%. Mortality was reported on a per pup basis, which limits the utility of the benchmark dose model.
m,k Statistically significant increase, decrease compared to controls; 2 no statistically significant effects compared to controls.
0.30 [525]
excluding the last one born were killed on the day of parental rats included the number of litters born and
birth so that animals could continue mating. The last fertility. Statistical analyses included Kruskal–Wallis
litter was raised by the dam and weaned on PND 21 (day ANOVA on ranks, Mann–Whitney U test, w 2 test, oneof
birth not defined). Birth weight and weight gain were way ANOVA, arc sine square-root transformation, and
recorded in the last litter. Reproductive endpoints in Duncan multiple range test.
Birth Defects Research (Part B) 83:157–395, 2008