References popup

The weeks shown in color represent the start and end points of chemical exposure for each study.

Study Results Study Details References

Results for Bisphenol A

Increased incidence of hyperplastic ducts at 50 days; cribriform-like structures at two higher doses at both time points; increased proliferation of epithelial cells and estrogen receptor α -positive cells in these lesions

Subjects: Wistar-Furth rats

Chemical: Bisphenol A

Low doses tested: 2.5, 25, 250 or 1000 μg/kg bw/d

Route of administration: delivered through an implanted osmotic pump

Exposure duration: gestational day 9 – post-natal day 1 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 21)

Age of measurement: 50 and 95 days of age

Reference [PubMed Link]
Murray TJ, Maffini MV, Ucci AA, Sonnenschein C, Soto AM. 2007. Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure. Reprod Toxicol 23(3):383-390.
Study Results Study Details References

Results for Bisphenol A

Increased mammary gland ductal area and extension; increased number of cells per unit area of epithelium and decreased Bax-positive cells in inner cord cells; increased cells with fat vacuoles and increased vacuoles in each cell; decreased density of collagen deposits and area covered by collagen

Subjects: CD-1 mice

Chemical: Bisphenol A

Low doses tested: 250 ng/kg bw/d

Route of administration: delivered through an implanted osmotic pump

Exposure duration: gestational day 8 – gestational day 18 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 11)

Age of measurement: 18 days post-fertilization

Reference [PubMed Link]
Vandenberg LN, Maffini MV, Wadia PR, Sonnenschein C, Rubin BS, Soto AM. 2007. Exposure to environmentally relevant doses of the xenoestrogen bisphenol-A alters development of the fetal mouse mammary gland. Endocrinology 148(1):116-127.
Study Results Study Details References

Results for Bisphenol A

Increased volume fraction alveolar buds at 0.25 μg/kg at 3 months of age and at 2.5 μg/kg at 9 months; decreased volume fraction ducts at 0.25 μg/kg at 9 months of age; increased intraductal hyperplasias (beaded ducts) at 9 months with increased proliferation in beaded ducts and associated epithelium

Subjects: CD-1 mice

Chemical: Bisphenol A

Low doses tested: 0.25, 2.5 or 25 μg/kg bw/dy

Route of administration: dissolved in DMSO and delivered through an implanted osmotic pump

Exposure duration: gestational day 8 – post-natal day 16 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 34)

Age of measurement: 3, 9 and 12 months of age

Reference [PubMed Link]
Vandenberg LN, Maffini MV, Schaeberle CM, Ucci AA, Sonnenschein C, Rubin BS, Soto AM. 2008 Nov-Dec. Perinatal exposure to the xenoestrogen bisphenol-A induces mammary intraductal hyperplasias in adult CD-1 mice. Reprod Toxicol 26(3-4):210-9.
Study Results Study Details References

Results for Bisphenol A

Decreased β-Cas milk content in those exposed in utero to 0.5 and 50.0 μg/kg. Decreased mammary gland differentiation scores in F1 pregnant dams on gestational day 21 at 0.5 and 50.0 μg/kg. Decreased mammary mRNA levels of α-Lactalb, β-Cas on both gestational days 18 and 21 and PRLR mRNA levels decreased on gestational day 18 of F1 dams at 0.5 and 50.0μg/kg. There were also decreased β-Cas and pStat5a/b protein levels on gestational days 18 and 21 and gestational day 18, respectively, at both exposure levels. In addition ERα and PR protein expression was decreased in the mammary gland on gestational day 21 at the 50.0 μg/kg exposure level.

Subjects: Wistar rats

Chemical: Bisphenol A

Low doses tested: 0.5 or 50.0 μg/kg bw/d

Route of administration: dissolved in ethanol and diluted in water and delivered in drinking water

Exposure duration: gestational day 9 – post-natal day 21 (comparable to human prenatal development from approximately day 1 of week 3 to beyond birth)

Age of measurement: post-natal days 108, 111, 112-125

Reference [PubMed Link]
Kass L, Altamirano GA, Bosquiazzo VL, Luque EH, Munoz-de-Toro M. 2012. Perinatal exposure to xenoestrogens impairs mammary gland differentiation and modifies milk composition in Wistar rats. Reprod Toxicol 33(3):390-400.
Study Results Study Details References

Results for Bisphenol A

Increase in susceptibility to mammary tumor formation in females exposed to 25 and 250 μg/kg doses in a model of mammary cancer induced by DMBA.

Subjects: FVB/N mice

Chemical: Bisphenol A

Low doses tested: 25.0 or 250.0 μg/kg bw/d

Route of administration: dissolved in PBS and DMSO and administered by gavage

Exposure duration: gestational day 8 – gestational day 18 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 11)

Age of measurement: post-natal day 16 and post-natal weeks 3, 5 and 8

Reference [PubMed Link]
Weber Lozada K, Keri RA. 2011. Bisphenol A increases mammary cancer risk in two distinct mouse models of breast cancer. Biol Reprod 85(3):490-497.
Study Results Study Details References

Results for Bisphenol A

Early vaginal opening in mice treated with 25.0 μg/kg.

Subjects: FVB/N mice

Chemical: Bisphenol A

Low doses tested: 25.0 or 250.0 μg/kg bw/d

Route of administration: dissolved in PBS and DMSO and administered by gavage

Exposure duration: gestational day 8 – gestational day 18 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 11)

Age of measurement: post-natal day 16 and post-natal weeks 3, 5 and 8

Reference [PubMed Link]
Weber Lozada K, Keri RA. 2011. Bisphenol A increases mammary cancer risk in two distinct mouse models of breast cancer. Biol Reprod 85(3):490-497.
Study Results Study Details References

Results for Bisphenol A

Increase in susceptibility to mammary tumor formation in females exposed to 25 and 250 μg/kg doses in a model of mammary cancer induced by DMBA.

Subjects: FVB/N mice

Chemical: Bisphenol A

Low doses tested: 25.0 or 250.0 μg/kg bw/d

Route of administration: dissolved in PBS and DMSO and administered by gavage

Exposure duration: gestational day 8 – gestational day 18 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 11)

Age of measurement: post-natal day 16 and post-natal weeks 3, 5 and 8

Reference [PubMed Link]
Jin MH, Ko HK, Hong CH, Han SW. 2008. In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin affects the development of reproductive system in mouse. Yonsei Med J 49(5):843-850.
Study Results Study Details References

Results for Bisphenol A

Early vaginal opening in mice treated with 25.0 μg/kg.

Subjects: FVB/N mice

Chemical: Bisphenol A

Low doses tested: 25.0 or 250.0 μg/kg bw/d

Route of administration: dissolved in PBS and DMSO and administered by gavage

Exposure duration: gestational day 8 – gestational day 18 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 11)

Age of measurement: post-natal day 16 and post-natal weeks 3, 5 and 8

Reference [PubMed Link]
Jin MH, Ko HK, Hong CH, Han SW. 2008. In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin affects the development of reproductive system in mouse. Yonsei Med J 49(5):843-850.
Study Results Study Details References

Results for Bisphenol A

Increased percentage of ducts, terminal ducts, terminal end buds and alveolar buds at 6 months; DNA synthesis decreased in the epithelium at 10 days of age and increased in the stroma at 6 months

Subjects: CD-1 mice

Chemical: Bisphenol A

Low doses tested: 25 or 250 μg/kg bw/d

Route of administration: delivered through an implanted osmotic pump

Exposure duration: gestational day 9 – gestational day 20 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 16)

Age of measurement: 10 days, 1 month and 6 months of age

Reference [PubMed Link]
Markey CM, Luque EH, Munoz de Toro M, Sonnenschein C, Soto AM. 2001. In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland. Biol Reprod 65(4):1215-1223.
Study Results Study Details References

Results for Bisphenol A

Age dependent increase in percentage of alveolar buds and lobuloalveoli

Subjects: CD-1 mice

Chemical: Bisphenol A

Low doses tested: 25 or 250 μg/kg bw/d

Route of administration: delivered through an implanted osmotic pump

Exposure duration: gestational day 9 – gestational day 20 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 16)

Age of measurement: between 1 and 12 months of age

Reference [PubMed Link]
Markey CM, Coombs MA, Sonnenschein C, Soto AM. 2003. Mammalian development in a changing environment: exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs. Evolution & Development 5(1):67-75.
Study Results Study Details References

Results for Bisphenol A

Increased percentage with 4 or 8 consecutive days in estrous; decreased vaginal weight at 3 months of age

Subjects: CD-1 mice

Chemical: Bisphenol A

Low doses tested: 25 or 250 μg/kg bw/d

Route of administration: delivered through an implanted osmotic pump

Exposure duration: gestational day 9 – gestational day 20 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 16)

Age of measurement: between 1 and 12 months of age

Reference [PubMed Link]
Markey CM, Coombs MA, Sonnenschein C, Soto AM. 2003. Mammalian development in a changing environment: exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs. Evolution & Development 5(1):67-75.
Study Results Study Details References

Results for Bisphenol A

Increased incidence of blood-filled ovarian bursae at 6 months of age; increased percentage of ovarian tissue occupied by antral follicles at 3 months in higher dosed group only

Subjects: CD-1 mice

Chemical: Bisphenol A

Low doses tested: 25 or 250 μg/kg bw/d

Route of administration: delivered through an implanted osmotic pump

Exposure duration: gestational day 9 – gestational day 20 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 16)

Age of measurement: between 1 and 12 months of age

Reference [PubMed Link]
Markey CM, Coombs MA, Sonnenschein C, Soto AM. 2003. Mammalian development in a changing environment: exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs. Evolution & Development 5(1):67-75.
Study Results Study Details References

Results for Bisphenol A

Decreased relative weight of vagina and absolute volume of lamina propria of the uterus at higher dose; increased DNA synthesis in uterine epithelium at higher dose; increased estrogen receptor (ERα) and progesterone receptor (PR) expression in the luminal epithelial cells of the uterus

Subjects: CD-1 mice

Chemical: Bisphenol A

Low doses tested: 25 or 250 ng/kg bw/d

Route of administration: delivered through an implanted osmotic pump

Exposure duration: gestational day 9 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 21)

Age of measurement: 3 months of age (adulthood)

Reference [PubMed Link]
Markey CM, Wadia PR, Rubin BS, Sonnenschein C, Soto AM. 2005. Long-term effects of fetal exposure to low doses of the xenoestrogen bisphenol-A in the female mouse genital tract. Biol Reprod 72(6):1344-1351.
Study Results Study Details References

Results for Bisphenol A

Increased number and area of terminal end buds (TEBs) relative to ductal area; increased sensitivity of TEBs to estradiol; decreased number of apoptotic cells in TEBs; decreased correlation between ductal length and age at first proestrus; increased progesterone receptor-positive ductal epithelial cells

Subjects: CD-1 mice

Chemical: Bisphenol A

Low doses tested: 25 or 250 ng/kg bw/d

Route of administration: delivered through an implanted osmotic pump

Exposure duration: gestational day 9 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 21)

Age of measurement: 1 month of age (peripuberty)

Reference [PubMed Link]
Munoz-de-Toro M, Markey C, Wadia PR, Luque EH, Rubin BS, Sonnenschein C, Soto AM. 2005. Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice. Endocrinology 146(9):4138-4147.
Study Results Study Details References

Results for Bisphenol A

Increased uterine stromal Hoxa10 expression

Subjects: CD-1 mice

Chemical: Bisphenol A

Low doses tested: 0.5 or 1.0 mg/kg bw/d

Other doses tested: 5, 50 or 200 mg/kg bw/d

Route of administration: injected intraperitoneally

Exposure duration: gestational day 9 – gestational day 16 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 8)

Age of measurement: 2 and 6 weeks of age

Reference [PubMed Link]
Smith CC, Taylor HS. 2007. Xenoestrogen exposure imprints expression of genes (Hoxa10) required for normal uterine development. FASEB J 21(1):239-246.
Study Results Study Details References

Results for Bisphenol A

Increased terminal ducts at 250 μg/kg at 21 and 100 days of age; increased lobules type 1 at 250 μg/kg at 35 days; significantly altered gene expression signatures of the mammary gland at both doses and at different ages

Subjects: Sprague-Dawley rats

Chemical: Bisphenol A

Low doses tested: 25 or 250 μg/kg bw/d

Route of administration: dissolved in sesame oil and delivered through gavage

Exposure duration: gestational day 10 – gestational day 21 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 16)

Age of measurement: 21 days of age through adulthood

Reference [PubMed Link]
Moral R, Wang R, Russo IH, Lamartiniere CA, Pereira J, Russo J. 2008 Jan. Effect of prenatal exposure to the endocrine disruptor bisphenol A on mammary gland morphology and gene expression signature. J Endocrinol 196(1):101-12.
Study Results Study Details References

Results for Bisphenol A (BPA)

Increased incidence of lesions in reproductive tract at 0.1 and 1.0 μg/kg

Subjects: CD-1 mice

Chemical: Bisphenol A (BPA)

Low doses tested: 0.1, 1.0, 10.0, 100.0, or 1000.0 μg/kg bw

Route of administration: dissolved in corn oil and injected sub-cutaneously

Exposure duration: gestational day 9 – gestational day 16 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 8)

Age of measurement: sixteen through eighteen months of age

Reference [PubMed Link]
Newbold RR, Jefferson WN, Padilla-Banks E. 2009. Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life. Environ Health Perspect 117(6):879-885.
Study Results Study Details References

Results for Bisphenol A (BPA)

Increased number of ovarian cysts at 1.0 μg/kg

Subjects: CD-1 mice

Chemical: Bisphenol A (BPA)

Low doses tested: 0.1, 1.0, 10.0, 100.0, or 1000.0 μg/kg bw

Route of administration: dissolved in corn oil and injected sub-cutaneously

Exposure duration: gestational day 9 – gestational day 16 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 8)

Age of measurement: sixteen through eighteen months of age

Reference [PubMed Link]
Newbold RR, Jefferson WN, Padilla-Banks E. 2009. Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life. Environ Health Perspect 117(6):879-885.
Study Results Study Details References

Results for Bisphenol A

Altered mammary gland proteome, primarily at 250 μg/kg

Subjects: Sprague-Dawley CD rats

Chemical: Bisphenol A

Low doses tested: 25 or 250 μg/kg bw/d

Route of administration: delivered via gavage

Exposure duration: gestational day 10 – gestational day 21 (comparable to human prenatal development from approximately day 1 of week 3 to day 1 of week 16)

Age of measurement: 21 and 50 days of age

Reference [PubMed Link]
Betancourt AM, Mobley JA, Russo J, Lamartiniere CA. 2010. Proteomic analysis in mammary glands of rat offspring exposed in utero to bisphenol A. J Proteomics 73(6):1241-1253.