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. Author manuscript; available in PMC: 2017 Jan 1.
Published in final edited form as: Reprod Toxicol. 2015 Oct 19;59:167–182. doi: 10.1016/j.reprotox.2015.09.006

Table 1. Summary of In Vivo Studies Since 2007 on the Carcinogenicity of BPA.

Organ Species/Strain Dose Route Timing Tumor Initiator Outcome Reference
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)