Females |
Mammary |
Mice/Balb/c |
25μg/kg/day |
Oral |
Puberty-3 weeks |
DMBA |
Increased lateral branches and hyperplasia; neoplastic lesions in MaSC regenerated mammary glands |
(Wang et al. 2014) |
Mammary |
Mice/C57BL/6-ERα+/-
|
250ng/kg/day |
Osmotic Pump |
E8 to parturition |
-- |
Global changes in the stromal and epithelial transcriptome, altered stromal and epithelial compartments in the mammary gland |
(Wadia et al, 2013) |
Mammary |
Rats/SD |
50-2 50μg/kg/day |
Oral |
Birth to PND21 |
DMBA |
Increased number of mammary tumors |
(Betancourt et al. 2012) |
Mammary |
Mice/MMTV-erbB2 |
2.5 -2,500μg/L drinking water |
Oral |
56 to 252 days of age |
activated erbB2 |
Decreased tumor latency, increased tumor multiplicity, tumor burden and |
(Jenkins et al. 2011) |
Mammary |
Mice/FVB/N |
2 -250μg/kg/day |
Oral |
E8 to parturition |
DMBA |
Decreased tumor latency and increased tumor susceptibility |
(Weber Lozada et al. 2011) |
Mammary |
Mice/C57BL/6 |
0.6μg - 1.2mg/kg/day |
Oral |
E1 to PND24 |
-- |
Increased number of TEB and PR expressing mammary epithelial cells |
(Ayyanan et al. 2011) |
Mammary |
Rats/SD |
25-250μg/kg/day |
Oral |
PND2 to PND21 and E2 to E20 |
DMBA |
Decreased tumor latency, and increased number of mammary tumors. |
(Lamartiniere et al.2011) |
Mammary |
Mice/CD-1 |
5mg/kg/day |
IP |
E9 to parturition |
-- |
No effect on EZH2 mRNA expression, increased EZH2 protein expression and |
(Doherty et al. 2010) |
Mammary |
Rats/SD |
25-250 μg/kg/day |
Oral |
E10 to E21 |
DMBA |
Decreased tumor latency and increased tumor susceptibility |
(Betancourt et al. 2010) |
Mammary |
Rats/SD |
25- 250 μg/kg day |
Oral |
PND2 - PND20 |
DMBA |
Decreased tumor latency and increase in mammary tumor formation |
(Jenkins et al. 2009) |
Mammary |
Rats/SD |
25-250μg/kg/day |
Oral |
E10 to parturition |
-- |
Increased number of TEBs, TDs, and lobular structures during development |
(Moral et al. 2008) |
Mammary |
Rats/Wistar |
25μg/kg/day |
Osmotic pump |
E8 to E23 |
NMU |
Increase in ductal hyperplasia formation |
(Durando et al. 2007) |
Mammary Mammary |
Rats/Wistar/furth Rats/SD |
2.5 -1000μg/kg/day; 0.25 to 250μg/kg/day |
Osmotic Pump; Osmotic pump |
E9 to PND1;E9 to PND 1 and E9 to PND21 |
--- |
Increase in ductal hyperplasia formation, presence of DCISPalpable tumors (carcinomas) |
(Murray et al. 2007) (Acevedo et al 2013) |
Mammary |
Rats/W/F |
250μg/kg/day |
Osmuotic pump |
E9 to PND1 |
- |
Global epigenome alterations (DNA methylation at PND4, 21, 50 Altered gene expression pattern at PND50 |
(Dhimolea et al, 2014) |
Ovary |
Rats/Eker |
50mg/kg/day |
s.c. |
PND10-12 |
Tsc Ek/+ mutation |
normal ovary morphology: presence of corpora lutea, normal estrous cyclicity |
(Greathouse et al. 2012) |
Ovary |
Mice/CD-1 |
10mg/kg/day |
s.c. |
PND15-18 |
-- |
No morphological abnormalities |
(Nikaido et al. 2005) |
Ovary |
Mice/CD-1 |
10-1000μg/kg/day |
s.c. |
PND1-5 |
-- |
Increased ovarian cysts (100μg/kg) and progressive proliferative lesions |
(Newbold et al. 2007) |
Ovary |
Mice/CD-1 |
0.1-1000 μg/kg/day |
s.c. |
E9-16 |
-- |
Increased ovarian cysts (1μg/kg only ) and cystadenomas; increased progressive proliferative lesions |
(Newbold et al. 2009) |
Ovary |
Rats/SD |
5-500μg/kg/day |
s.c. |
PND1-10 |
-- |
Increased polycystic ovaries and infertility (500μg/kg/day only) |
(Fernandez et al. 2010) |
Uterus |
Mice/CD-1 |
10-1000μg/kg/day |
s.c. |
PND1-5 |
-- |
Increased incidence of cystic endometrial hyperplasia, increased trend in adenomyosis, increased leiomyomas |
(Newbold et al. 2007) |
Uterus |
Mice/CD-1 |
0.1-1000 μg/kg/day |
s.c. |
E9-16 |
-- |
No instances of leiomyoma, some atypical hyperplasia and stromal polyps, sarcoma of uterine cervix |
(Newbold et al. 2009) |
Uterus |
Rats/Wistar |
0.5-50mg/kg/day |
s.c. |
∼PND91-95 |
-- |
No change in uterine morphology |
(Okuda et al. 2010) |
Uterus |
Rats/Eker |
50mg/kg/day |
s.c. |
PND10-12 |
-- |
No increased frequency of multiplicity of leiomyoma |
(Greathouse et al. 2012) |
Vagina |
Rats/Eker |
50mg/kg/day |
s.c. |
PND10-12 |
Tsc Ek/+ mutation |
Normal vaginal morphology |
(Greathouse et al. 2012) |
Males |
Prostate |
Rat/SD |
10μg/kg/day |
s.c. |
PND1, 3, 5 |
E |
Hypomethylation of PDE4D4 with increased expression |
(Prins et al. 2008) |
Prostate |
Rats/SD |
10-90μg/kg/day |
i.g. |
adult- 4 week treatment |
T |
Increased prostate weight, volume, epithelial cell height, decreased testosterone and increased PSA |
(Wu et al. 2011) |
Prostate |
Rats/SD |
10μg/kg/day |
s.c and oral |
PND1,3&5 |
T+E |
Increased incidence of PINs |
(Prins et al. 2011) |
Prostate |
Rat/SD |
10μg/kg/day |
s.c. |
PND1,3,5 |
T+E |
Altered methylation/expression of Nsbp1, Hpcal1 and genes involved in methylation |
(Tang et al. 2011) |
Prostate |
Mice/C57BL/6 |
20μg/kg/day |
Oral |
E13-E16 |
- |
Elevated CYP19A1 activity and increased E2 levels in the urogenital |
(Arase et al. 2011) |
Prostate |
Rats/Wistar |
25-600μg/kg/day |
s.c. |
adult-4day treatment |
-- |
Increased 5α-reductase and plasma E:T ratio |
(Castro et al. 2013) |
Prostate |
Rats/SD |
25-250μg/kg/day |
Oral gavage |
E10-E21 |
-- |
Increased incidence of multifocal hyperplasia/dysplasia; PINs |
(Brandt et al. 2014) |
Prostate |
Mice/Nude |
100-250μg/kg/day |
Oral |
Daily treatment for 2 weeks post xenograft |
T+E |
Increased PINS and prostate adenocarcinoma of human prostate epithelium in renal capsule xenograft model |
(Prins et al. 2014) |
Prostate |
Rats/SD |
2-50μg/kg/day |
s.c./oral |
PND1,3,5 |
T+E |
Increased lateral prostatic inflammation and PIN lesions |
(Wong et al. 2015) |
Testes |
Rats/Long-Evans |
2.5-25μg/kg/day |
Oral |
E12-PND21 |
-- |
Increased Leydig cell number |
(Nanjappa et al. 2012) |
Testes |
Mice/C57BL/6 |
50-1000μg/kg/day |
Oral |
E10-16 |
-- |
No changes in sperm production, germ cell apoptosis, serminiferous tubule histology, serum testosterone |
(LaRocca et al. 2011) |
Testes |
Rats/SD |
285.4ppm (food) |
Oral |
adult-3month treatment |
-- |
No histological abnormalities |
(Zhang et al. 2013) |
Females and Males |
Liver |
Mice/Avy C3HeJ/C57BL/6 |
0.5ng-50mg/kg/day |
Oral |
E0-PND22 |
-- |
Increased hepatic neoplastic and preneoplastic lesions |
(Weinhouse et al. 2014) |