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

BISPHENOL A
Table 83
Summary of Limited Utility Developmental Toxicity Studies (Single Dose Level)
Dose and dosing period
Model (route) (mg/kg bw/day) Significant developmental findings Reference
Rat
Long–Evans male 0.0024, PND 21–90 m Serum LH level; k weight of seminal vesicles; k Testicular Akingbemi et al.
offspring (gavage) testosterone level; and k basal and LH-induced ex vivo (2004)
Experiment 3 testosterone production
Wistar male pup (s.c. 100, PND 2–12 Advanced testicular lumen formation, mtestis weight, m Atanassova et al.
injection) Sertoli cell volume/testis, m spermatocyte nuclear volume/ (2000)
unit Sertoli cell, and m plasma FSH on PND 18; m plasma
FSH on PND 25; m testicular weight in adulthood
Wistar dam (drinking B2.5, gestation a –PND 21 In rats 4–7 months of age: no effect on the number of Funabashi et al.
water) corticotropin-releasing hormone neurons in the preoptic (2004a)
areas of males, a loss in sex difference in the anterior and
posterior bed nuclei of the stria terminalis
Sprague–Dawley 0.010, PND 1, 3, and 5; half In rats with no 17b-estradiol and testosterone exposure in Ho et al. (2006b)
male pup (s.c. the rats exposed to 17b­ adulthood: no effects on dorsal prostate weight,
injection) estradiol and testosterone histopathology alterations, proliferation index, or apoptotic
in adulthood index In rats with 17b-estradiol and testosterone exposure
in adulthood: m incidence and severity of prostatic
intraepithelial neoplasia; m proliferation and apoptosis in
regions of prostatic intraepithelial neoplasia
Sprague–Dawley 300, PND 1–5 No effects on age of vaginal opening or preputial separation, Nagao et al. (1999)
pup (s.c injection) copulation or fertility indices, sexual behavior of males,
histopathologic alterations in males, or female reproductive
organs, or effects on SDN-POA. [Panel noted possible m
number of apically located nuclei in prostate, but a
definitive conclusion could not be made based on 1
photograph]
Wistar. male pup (s.c 50, PND 22–32 m Serum prolactin levels on PND 29 but not PND 120; m lateral Stoker et al. (1999)
injection) but not ventral prostate weight; m focal luminal
polymorphonuclear cellular infiltrate in prostate No
histological evidence of prostate inflammation
Mouse
CF1 (oral) 0.0024, GD 11–17 m Body weight at weaning; k postnatal pup survival; k period Howdeshell et al.
between vaginal opening and first estrus No effect on age (1999)
of vaginal opening
ICR/Jc1 mouse dams 0.02, GD 0 to GD 10.5, GD m Tuj1 in the intermediate zone at GD 14.5 and GD 16.5; m PDI Nakamura et al.
(s.c. injection) 12.5, GD 14.5, or GD 16.5 immunoreactivity in the neocortex from GD12.5 until (2006)
GD16.5 and in subplate cells at GD 14.5; variable changes in
BrdU labeling depending on when labeled and location; m
gene expression of Math3, Ngn2, Hes1, LICAM, and THRalpha
at GD14.5; k gene expression of Hes1 and Hes5 at GD
12.5 No effect on immunoreactivity pattern for KI-67,
nestin, Musashi and histone H3.
ICR (oral) 0.002 mg/kg bw/day from Variable changes in retinoic acid retinoid X receptors á mRNA Nishizawa et al.
6.5–11.5, 6.5–13.5, 6.5–15.5, expression in brain, ovary, and testis, depending on brain (2003)
and 6.5–17.5 days post- region and day of exposure
coitum
Other
Prepubertal Poll 3.5 biweekly, at 4–11 weeks 2 On blood levels during treatment; 2 on body, kidney, Evans et al. (2004)
Dorset female lambs of age (ovariectomy at 9 adrenal, or ovarian weights; k pulsatile LH secretion
(i.m. injection) weeks of age)
Prepubertal Poll 3.5 biweekly, at 4–11 weeks m Uterine/cervical tract weight, endometrial area, and Morrison et al.
Dorset female lambs of age (ovariectomy at 9 endometrial/myometrial ratio Qualitative observations (2003)
(i.m. injection) weeks of age) included endometrial edema, decreased endometrial gland
density, crowding of cells in the uterine epithelium,
keratinized cervical epithelium, m intracellular staining for
ERa and ERb in the uterine subepithelium
Suffolk ewes (s.c. 5 GD 30–GD 90 k Birth weight, height and chest circumference in female Savabieasfahani
injection) offspring at birth m Anoscrotal:anonavel ratio in male et al. (2006)
offspring at birth m LH and first breeding season in female
offspring at PND 60
a Implied but not stated that exposure occurred during the entire gestation period.
m,k Statistically significant increase, decrease compared to controls; 2 no statistically significant effects compared to controls.
Panel members reviewed the literature on estrogen- Different strains of rats show clear, robust reproducisensitivity
across rat strains and suppliers, the following ble differences in response to potent estrogens and
is a summary of our findings. antiandrogens. Several traits have been shown to be
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