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

Results were reported to be similar for the 2 species, and
unless otherwise indicated, data were shown for S.
purpuratus. In additional studies, sea urchin embryos
were incubated in bisphenol A at 0–500 mg/L with and
without addition of tamoxifen or bisphenol A at 0–
750 mg/L with and without the addition of ICI 182,780.
Data were analyzed by ANOVA followed by Tukey–
Kramer test or Tukey or Student-Newman–Keuls tests
for pair-wise multiple comparison. An EC 50 of 226.6 mg/
L (lower limit: 121.6, upper limit: 323.5 mg/L) was
estimated for developmental toxicity associated with
bisphenol A exposure. Based on EC50 values, 17bestradiol
was B15 times more potent than bisphenol A.
Tamoxifen inhibited developmental toxicity, and ICI
182,780 enhanced the developmental toxicity induced
by bisphenol A; similar results were obtained for 17bestradiol.
The study authors concluded that bisphenol A
induced developmental toxicity in sea urchins through a
tamoxifen-sensitive mechanism at levels exceeding environmentally
relevant concentrations.
Strengths/Weaknesses: The use of 2 species and
multiple concentrations are strengths.
Utility (Adequacy) for CERHR Evaluation Process:
This study may have utility for environmental assessment,
but is not useful for human risk assessment.
Andersen et al. (1999b), supported by the Danish
Strategic Environmental Research Program, evaluated
the effects of bisphenol A on female sexual maturation in
the zoo planktonic crustacean Acartia tonsa. Eggs were
grown in the presence of the algal food source for the
organism after exposure of the algae to bisphenol A
(499% purity) for 3 hr to promote sorption by the algae
of the test chemical [culture ware not discussed]. The
treated algae were added to Acartia tonsa eggs to give
nominal bisphenol A concentrations of 0.2, 2, and 20 mg/
L. [Actual concentrations were not reported. An
untreated or vehicle-treated control appears to have
been used.] 17b-Estradiol 23 mg/L was used as a positive
control, and 2,3-dichlorophenol 13.6 mg/L was used as a
negative control. On Day 8 of incubation, 10–25 juvenile
Acartia tonsa/group were transformed to an egg-collection
apparatus, in which exposure to treated algae
continued. Eggs were collected daily and counted until
Day 12, at which time a stable adult level of egg
production was established. Egg production by group
was compared using Student t-test. [A repeated-measures
test appears not to have been used.] A significant
increase in egg production was shown on Day 10 in
animals treated with bisphenol A 20 mg/L and 17bestradiol
23 mg/L compared to control. The authors
concluded that bisphenol A accelerated female reproductive
maturation in Acartia tonsa and that the effect
appeared to be estrogenic.
Strengths/Weaknesses: Strengths are the use of multiple
exposure levels, the inventive method of feeding
bisphenol A to the test organisms, and the use of 17bestradiol
as a positive control.
Utility (Adequacy) for CERHR Evaluation Process:
This study may have utility for environmental assessment,
but is not useful for human risk assessment.
Watts et al. (2001), supported by the European Union,
examined development and reproduction in 2 generations
of non-biting midges (Chironomus riparius) exposed
to bisphenol A. The study began with incubation of 4 egg
ropes/group in media containing vehicle, bisphenol A,
Birth Defects Research (Part B) 83:157–395, 2008
BISPHENOL A
309
or ethinyl estradiol [apparently at the same concentrations
described below]. Twenty first-instar larvae from
the appropriate media were added to each exposure
glass jar containing dechlorinated water and sediment
spiked with bisphenol A [purity not indicated] at
concentrations of 0 (ethanol vehicle control and dechlorinated
tap water control), o0.010, 0.078, 0.55, 77, 750, or
10,400 mg/L. Four replicate jars were prepared for
each dose level. Concentrations in sediment
were verified. Numbers and sexes of adults emerging
from each replicate jar were determined. Egg ropes
produced by the first generation were counted and
placed in media containing test solutions or vehicle
controls. Four egg ropes/group were selected and used
to reseed the sediments with the second generation of
larvae. Adults emerging from the second generation
were counted. Statistical significance was determined by
ANOVA. In the first generation, adult emergence was
delayed in females from the o0.010, 0.55, and 77 mg/L
bisphenol A groups but was not affected in males. Males
were reported to emerge significantly earlier than
females. In the second generation, emergence of males
and female adults was significantly delayed at
Z0.078 mg/L bisphenol A. At concentrations of 0.010–
750 mg/L, there were no significant differences in the
percentage of adults emerging in either generation. No
second-generation adults emerged in the group exposed
to 10,400 mg/L. There were no effects on sex ratio.
Exposure to bisphenol A did not significantly affect the
number of eggs produced by the first generation. In
contrast to bisphenol A, exposure to ethinyl estradiol
accelerated adult emergence. The study authors concluded
that the endpoints evaluated indicated general
sediment toxicity but were not useful for detecting
estrogenic effects.
Strengths/Weaknesses: The wide range of exposure
levels and the use of ethinyl estradiol as a positive
control are strengths.
Utility (Adequacy) for CERHR Evaluation Process:
This study may have utility for environmental assessment,
but is not useful for human risk assessment.
Watts et al. (2003), supported by the European Union,
examined the effects of bisphenol A exposure on
moulting and mouthpart deformities in non-biting
midge (Chironomus riparius) larvae. Four egg-ropes/
group were incubated in glass jars in media containing
bisphenol A [purity not indicated] at 0 (ethanol
vehicle or dechlorinated water group), 0.010, 0.1, 1, 10,
100, or 1000 mg/L. Concentrations of bisphenol A were
verified in the 1000 mg/L group. On hatching,
exposures were continued in 10 larvae/group. Endpoints
examined included survival, time of moulting to
successive instars, wet weight 2 days after moulting to
fourth instar, and mouthpart morphology in fourthinstar
head capsules. Statistical analyses included ANO­
VA, Tukey–Kramer multiple comparison test, and Kruskal–Wallis
test. [Effects were similar in ethanol and
water controls.] Moulting was delayed and larval
weights were significantly decreased in the 1000 mg/L
bisphenol A group. Deformities of the mentum were
significantly increased in the range of 0.010–1 mg/L
bisphenol A. The effects of ethinyl estradiol were also
examined, and the study authors noted similar patterns
of malformations, with greater incidence following
exposure to ethinyl estradiol than bisphenol A. The