Endocrine Disruptors and the Breast: Early Life Effects and Later Life Disease

Article

Abstract

Breast cancer risk has both heritable and environment/lifestyle components. The heritable component is a small contribution (5–27 %), leaving the majority of risk to environment (e.g., applied chemicals, food residues, occupational hazards, pharmaceuticals, stress) and lifestyle (e.g., physical activity, cosmetics, water source, alcohol, smoking). However, these factors are not well-defined, primarily due to the enormous number of factors to be considered. In both humans and rodent models, environmental factors that act as endocrine disrupting compounds (EDCs) have been shown to disrupt normal mammary development and lead to adverse lifelong consequences, especially when exposures occur during early life. EDCs can act directly or indirectly on mammary tissue to increase sensitivity to chemical carcinogens or enhance development of hyperplasia, beaded ducts, or tumors. Protective effects have also been reported. The mechanisms for these changes are not well understood. Environmental agents may also act as carcinogens in adult rodent models, directly causing or promoting tumor development, typically in more than one organ. Many of the environmental agents that act as EDCs and are known to affect the breast are discussed. Understanding the mechanism(s) of action for these compounds will be critical to prevent their effects on the breast in the future.

Keywords

Endocrine disruption Breast cancer Mammary gland Hormones 

References

  1. 1.
    Centers for disease contral and prevention. Cancer among women. 2012. http://www.cdc.gov/cancer/dcpc/data/women.htm. 2012.
  2. 2.
  3. 3.
    American Cancer Society. Breast cancer facts and figures 2011–2012. 2011.Google Scholar
  4. 4.
    Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, et al. Environmental and heritable factors in the causation of cancer–analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000;343(2):78–85. doi:10.1056/NEJM200007133430201.PubMedGoogle Scholar
  5. 5.
    Buttke DE, Sircar K, Martin C. Exposures to endocrine-disrupting chemicals and age of menarche in adolescent girls in NHANES (2003–2008). Environ Heal Perspect. doi:10.1289/ehp.1104748.
  6. 6.
    Diamanti-Kandarakis E, Bourguignon J-P, Giudice LC, Hauser R, Prins GS, Soto AM et al. Endocrine-disrupting chemicals: an endocrine society scientific statement. Endocrine Rev. 2009;30(4):293–342. doi:10.1210/er.2009-0002.Google Scholar
  7. 7.
    US Environmental Protection Agency. Endocrine Disruptors Research. 2012. http://www.epa.gov/endocrine/#eds.
  8. 8.
    Nelson CM, Bissell MJ. Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer. Annu Rev Cell Dev Biol. 2006;22:287–309. doi:10.1146/annurev.cellbio.22.010305.104315.PubMedGoogle Scholar
  9. 9.
    US Environmental Protection Agency. TSCA Chemical Substance Inventory. 2011. http://www.epa.gov/oppt/existingchemicals/pubs/tscainventory/index.html.
  10. 10.
    Vineis P, Schatzkin A, Potter JD. Models of carcinogenesis: an overview. Carcinogenesis. 2010;31(10):1703–9. doi:10.1093/carcin/bgq087.PubMedGoogle Scholar
  11. 11.
    Soto AM, Sonnenschein C. The tissue organization field theory of cancer: a testable replacement for the somatic mutation theory. BioEssays: News Rev Mol Cell Dev Biol. 2011;33(5):332–40. doi:10.1002/bies.201100025.Google Scholar
  12. 12.
    National Toxicology Program. Nominations to the Testing Program. 2012. http://ntp.niehs.nih.gov/?objectid=25BC6AF8-BDB7-CEBA-F18554656CC4FCD9.
  13. 13.
    National Toxicology Program. Report on Carcinogens, 12th, http://ntp.niehs.nih.gov/ntp/roc/twelfth/roc12.pdf.
  14. 14.
    Diethylstilbestrol [database on the Internet]. Available from: http://monographs.iarc.fr/ENG/Monographs/vol100A/mono100A-16.pdf. Accessed.
  15. 15.
    Knudson AG. Hereditary cancer: two hits revisited. J Cancer Res Clin Oncol. 1996;122(3):135–40.PubMedGoogle Scholar
  16. 16.
    Markey CM, Luque EH, Munoz De Toro M, Sonnenschein C, Soto AM. In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland. Biol Reprod. 2001;65(4):1215–23.PubMedGoogle Scholar
  17. 17.
    Rudel RA, Fenton SE, Ackerman JM, Euling SY, Makris SL. Environmental exposures and mammary gland development: state of the science, public health implications, and research recommendations. Environ Heal Perspect. 2011;119(8):1053–61. doi:10.1289/ehp.1002864.Google Scholar
  18. 18.
    National Cancer Institute. The Cost of Care. 2011. http://www.cancer.gov/aboutnci/servingpeople/cancer-statistics/costofcancer. 2012.
  19. 19.
    Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. Race, breast cancer subtypes, and survival in the Carolina breast cancer study. JAMA. 2006;295(21):2492–502. doi:10.1001/jama.295.21.2492.PubMedGoogle Scholar
  20. 20.
    Eroles P, Bosch A, Perez-Fidalgo JA, Lluch A. Molecular biology in breast cancer: intrinsic subtypes and signaling pathways. Cancer Treat Rev. 2012;38(6):698–707. doi:10.1016/j.ctrv.2011.11.005.PubMedGoogle Scholar
  21. 21.
    Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11(16):5678–85. doi:10.1158/1078-0432.CCR-04-2421.PubMedGoogle Scholar
  22. 22.
    Desmedt C, Haibe-Kains B, Wirapati P, Buyse M, Larsimont D, Bontempi G, et al. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res. 2008;14(16):5158–65. doi:10.1158/1078-0432.CCR-07-4756.PubMedGoogle Scholar
  23. 23.
    Fenton SE. Endocrine-disrupting compounds and mammary gland development: early exposure and later life consequences. Endocrinology. 2006;147(6 Suppl):S18–24. doi:10.1210/en.2005-1131.PubMedGoogle Scholar
  24. 24.
    Monosson E, Kelce WR, Lambright C, Ostby J, Gray Jr LE. Peripubertal exposure to the antiandrogenic fungicide, vinclozolin, delays puberty, inhibits the development of androgen-dependent tissues, and alters androgen receptor function in the male rat. Toxicol Ind Health. 1999;15(1–2):65–79.PubMedGoogle Scholar
  25. 25.
    Buckley J, Willingham E, Agras K, Baskin LS. Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice. Environ Health. 2006;5:4. doi:10.1186/1476-069X-5-4.PubMedGoogle Scholar
  26. 26.
    Gray LE, Ostby J, Furr J, Wolf CJ, Lambright C, Parks L, et al. Effects of environmental antiandrogens on reproductive development in experimental animals. Hum Reprod Update. 2001;7(3):248–64.PubMedGoogle Scholar
  27. 27.
    Rothschild TC, Boylan ES, Calhoon RE, Vonderhaar BK. Transplacental effects of diethylstilbestrol on mammary development and tumorigenesis in female ACI rats. Cancer Res. 1987;47(16):4508–16.PubMedGoogle Scholar
  28. 28.
    Kawaguchi H, Umekita Y, Souda M, Gejima K, Kawashima H, Yoshikawa T, et al. Effects of neonatally administered high-dose diethylstilbestrol on the induction of mammary tumors induced by 7,12-dimethylbenz[a]anthracene in female rats. Vet Pathol. 2009;46(1):142–50. doi:10.1354/vp.46-1-142.PubMedGoogle Scholar
  29. 29.
    Muto T, Wakui S, Imano N, Nakaaki K, Hano H, Furusato K, et al. In utero and lactational exposure of 3,3′, 4,4′, 5- pentachlorobiphenyl modulate dimenthlben[a]anthracene-induced rat mammary carcinogenesis. J Toxicologica Pathol. 2001;14:213–24.Google Scholar
  30. 30.
    Rayner JL, Enoch RR, Fenton SE. Adverse effects of prenatal exposure to atrazine during a critical period of mammary gland growth. Toxicol Sci. 2005;87(1):255–66. doi:10.1093/toxsci/kfi213.PubMedGoogle Scholar
  31. 31.
    White SS, Fenton SE, Hines EP. Endocrine disrupting properties of perfluorooctanoic acid. J Steroid Biochem Mol Biol. 2011. doi:10.1016/j.jsbmb.2011.03.011.
  32. 32.
    Restum JC, Bursian SJ, Giesy JP, Render JA, Helferich WG, Shipp EB, et al. Multigenerational study of the effects of consumption of PCB-contaminated carp from Saginaw Bay, Lake Huron, on mink. 1. Effects on mink reproduction, kit growth and survival, and selected biological parameters. J Toxicol Environ Health A. 1998;54(5):343–75.PubMedGoogle Scholar
  33. 33.
    Provenzano PP, Inman DR, Eliceiri KW, Knittel JG, Yan L, Rueden CT, et al. Collagen density promotes mammary tumor initiation and progression. BMC Med. 2008;6:11. doi:10.1186/1741-7015-6-11.PubMedGoogle Scholar
  34. 34.
    Maffini MV, Soto AM, Calabro JM, Ucci AA, Sonnenschein C. The stroma as a crucial target in rat mammary gland carcinogenesis. J Cell Sci. 2004;117(Pt 8):1495–502. doi:10.1242/jcs.01000.PubMedGoogle Scholar
  35. 35.
    White SE, Kato K, Jia LT, Basden BJ, Calafat AM, Hines EP, et al. Effect of perfluorooctanoic acid on mouse mammary gland development and differention resulting from cross-foster and restricted gestational exposure. Reprod Toxicol. 2009;27:289–98. doi:10.1016/j.reprotox.2008.11.054.PubMedGoogle Scholar
  36. 36.
    White SE, Calafat AM, Kuklenyik Z, Villanueva L, Zehr RD, Helfant L, et al. Gestational PFOA exposure of mice is associated with altered mammary gland development in dams and female offspring. Toxicol Sci. 2007;96(1):133–44. doi:10.1093/toxsci/kfl177.PubMedGoogle Scholar
  37. 37.
    Fertuck KC, Kumar S, Sikka HC, Matthews JB, Zacharewski TR. Interaction of PAH-related compounds with the alpha and beta isoforms of the estrogen receptor. Toxicol Lett. 2001;121(3):167–77.PubMedGoogle Scholar
  38. 38.
    Archer FL, Orlando R. Morphology, natural history, and enzyme patterns in mammary tumors of the rat induced by 7,12-dimethylbenz(a)anthracene. Cancer Res. 1968;28:217–23.PubMedGoogle Scholar
  39. 39.
    Ito N, Hasegawa R, Sano M, Tamano S, Esumi H, Takayama S, et al. A new colon and mammary carcinogen in cooked food, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Carcinogenesis. 1991;12(8):1503–6.PubMedGoogle Scholar
  40. 40.
    Lauber SN, Ali S, Gooderham NJ. The cooked food derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine is a potent oestrogen: a mechanistic basis for its tissue-specific carcinogenicity. Carcinogenesis. 2004;25(12):2509–17.PubMedGoogle Scholar
  41. 41.
    Gooderham NJ, Zhu H, Lauber S, Boyce A, Creton S. Molecular and genetic toxicology of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Mutat Res. 2002;507:91–9.Google Scholar
  42. 42.
    Lightfoot TJ, Coxhead JM, Cupid BC, Nicholson S, Garner RC. Analysis of DNA adducts by accelerator mass spectrometry in human breast tissue after administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and benzo[a]pyrene. Mutat Res. 2000;472(1–2):119–27.PubMedGoogle Scholar
  43. 43.
    Zheng W, Gustafson DR, Sinha R, Cerhan JR, Moore D, Hong CP, et al. Well-done meat intake and the risk of breast cancer. J Natl Canc Inst. 1998;90(22):1724–9.Google Scholar
  44. 44.
    Pottenger LH, Domoradzki JY, Markham DA, Hansen SC, Cagen SZ, Waechter Jr JM. The relative bioavailability and metabolism of bisphenol A in rats is dependent upon the route of administration. Toxicol Sci. 2000;54(1):3–18.PubMedGoogle Scholar
  45. 45.
    Völkel W, Colnot T, Csanady GA, Filser JG, Dekant W. Metabolism and kinetics of bisphenol a in humans at low doses following oral administration. Chem Res Toxicol. 2002;15(10):1281–7.PubMedGoogle Scholar
  46. 46.
    Trasande L, Attina TM, Blustein J. Association between urinary bisphenol A concentration and obesity prevalence in children and adolescents. JAMA. 2012;308(11):1113–21. doi:10.1001/2012.jama.11461.PubMedGoogle Scholar
  47. 47.
    Vandenberg LN, Maffini MV, Schaeberle CM, Ucci AA, Sonnenschein C, Rubin BS, et al. Perinatal exposure to the xenoestrogen bisphenol-A induces mammary intraductal hyperplasias in adult CD-1 mice. Reprod Toxicol. 2008;26(3–4):210–9. doi:10.1016/j.reprotox.2008.09.015.PubMedGoogle Scholar
  48. 48.
    Naciff JM, Jump ML, Torontali SM, Carr GJ, Tiesman JP, Overmann GJ, et al. Gene expression profile induced by 17alpha-ethynyl estradiol, bisphenol A, and genistein in the developing female reproductive system of the rat. Toxicol Sci. 2002;68(1):184–99.PubMedGoogle Scholar
  49. 49.
    Thayer KA, Belcher S. Mechanisms of action of bisphenol A and other biochemical/molecular interactions, http://www.who.int/foodsafety/chem/chemicals/5_biological_activities_of_bpa.pdf.
  50. 50.
    Bhattacharya P, Keating AF. Impact of environmental exposures on ovarian function and role of xenobiotic metabolism during ovotoxicity. Toxicol Appl Pharmacol. 2012;261(3):227–35. doi:10.1016/j.taap.2012.04.009.PubMedGoogle Scholar
  51. 51.
    Quignot N, Arnaud M, Robidel F, Lecomte A, Tournier M, Cren-Olive C, et al. Characterization of endocrine-disrupting chemicals based on hormonal balance disruption in male and female adult rats. Reprod Toxicol. 2012;33(3):339–52. doi:10.1016/j.reprotox.2012.01.004.PubMedGoogle Scholar
  52. 52.
    Richter CA, Birnbaum LS, Farabollini F, Newbold RR, Rubin BS, Talsness CE, et al. In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol. 2007;24(2):199–224. doi:10.1016/j.reprotox.2007.06.004.PubMedGoogle Scholar
  53. 53.
    Munoz-de-Toro M, Markey CM, Wadia PR, Luque EH, Rubin BS, Sonnenschein C, et al. Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice. Endocrinology. 2005;146(9):4138–47. doi:10.1210/en.2005-0340.PubMedGoogle Scholar
  54. 54.
    Mori T, Bern HA, Mills KT, Young PN. Long-term effects of neonatal steroid exposure on mammary gland development and tumorigenesis in mice. J Natl Cancer Inst. 1976;57(5):1057–62.PubMedGoogle Scholar
  55. 55.
    Lamartiniere CA, Jenkins S, Betancourt AM, Wang J, Russo J. Exposure to the endocrine disruptor bisphenol A alters susceptibility for mammary cancer. Horm Mol Biol Clin Investig. 2011;5(2):45–52. doi:10.1515/HMBCI.2010.075.PubMedGoogle Scholar
  56. 56.
    Tharp AP, Maffini MV, Hunt PA, VandeVoort CA, Sonnenschein C, Soto AM. Bisphenol A alters the development of the rhesus monkey mammary gland. Proc Natl Acad Sci U S A. 2012;109(21):8190–5. doi:10.1073/pnas.1120488109.PubMedGoogle Scholar
  57. 57.
    Jenkins S, Raghuraman N, Eltoum I, Carpenter M, Russo J, Lamartiniere CA. Oral exposure to bisphenol a increases dimethylbenzanthracene-induced mammary cancer in rats. Environ Heal Perspect. 2009;117(6):910–5. doi:10.1289/ehp.11751.Google Scholar
  58. 58.
    Betancourt AM, Eltoum IA, Desmond RA, Russo J, Lamartiniere CA. In utero exposure to bisphenol A shifts the window of susceptibility for mammary carcinogenesis in the rat. Environ Heal Perspect. 2010;118(11):1614–9. doi:10.1289/ehp.1002148.Google Scholar
  59. 59.
    Doherty LF, Bromer JG, Zhou Y, Aldad TS, Taylor HS. In utero exposure to diethylstilbestrol (DES) or bisphenol-A (BPA) increases EZH2 expression in the mammary gland: an epigenetic mechanism linking endocrine disruptors to breast cancer. Horm Cancer. 2010;1(3):146–55. doi:10.1007/s12672-010-0015-9.PubMedGoogle Scholar
  60. 60.
    Jenkins S, Wang J, Eltoum I, Desmond R, Lamartiniere CA. Chronic oral exposure to bisphenol A results in a nonmonotonic dose response in mammary carcinogenesis and metastasis in MMTV-erbB2 mice. Environ Heal Perspect. 2011;119(11):1604–9. doi:10.1289/ehp.1103850.Google Scholar
  61. 61.
    Ogura I, Masunaga S, Nakanishi J. Quantitative source identification of dioxin-like PCBs in Yokohama, Japan, by temperature dependence of their atmospheric concentrations. Environ Sci Technol. 2004;38(12):3279–85.PubMedGoogle Scholar
  62. 62.
    Safe SH. Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. Pharmacol Ther. 1995;67(2):247–81.PubMedGoogle Scholar
  63. 63.
    Safe SH. Hazard and risk assessment of chemical mixtures using the toxic equivalency factor approach. Environ Heal Perspect. 1998;106 Suppl 4:1051–8.Google Scholar
  64. 64.
    Chaffin CL, Peterson RE, Hutz RJ. In utero and lactational exposure of female Holtzman rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin: modulation of the estrogen signal. Biol Reprod. 1996;55(1):62–7.PubMedGoogle Scholar
  65. 65.
    Fenton SE, Hamm JT, Birnbaum LS, Youngblood GL. Persistent abnormalities in the rat mammary gland following gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol Sci. 2002;67(63):63–74.PubMedGoogle Scholar
  66. 66.
    Brown NM, Manzolillo PA, Zhang JX, Wang J, Lamartiniere CA. Prenatal TCDD and predisposition to mammary cancer in the rat. Carcinogenesis. 1998;19(9):1623–9.PubMedGoogle Scholar
  67. 67.
    Franczak A, Nynca A, Valdez KE, Mizinga KM, Petroff BK. Effects of acute and chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin on the transition to reproductive senescence in female Sprague–Dawley rats. Biol Reprod. 2006;74(1):125–30. doi:10.1095/biolreprod.105.044396.PubMedGoogle Scholar
  68. 68.
    Brown NM, Lamartiniere CA. Xenoestrogens alter mammary gland differentiation and cell proliferation in the rat. Environ Heal Perspect. 1995;103(7–8):708–13.Google Scholar
  69. 69.
    Gray Jr LE, Kelce WR, Monosson E, Ostby JS, Birnbaum LS. Exposure to TCDD during development permanently alters reproductive function in male Long Evans rats and hamsters: reduced ejaculated and epididymal sperm numbers and sex accessory gland weights in offspring with normal androgenic status. Toxicol Appl Pharmacol. 1995;131(1):108–18. doi:10.1006/taap.1995.1052.PubMedGoogle Scholar
  70. 70.
    Chan MY, Huang H, Leung LK. 2,3,7,8-Tetrachlorodibenzo-para-dioxin increases aromatase (CYP19) mRNA stability in MCF-7 cells. Mol Cell Endocrinol. 2010;317(1–2):8–13. doi:10.1016/j.mce.2009.11.012.PubMedGoogle Scholar
  71. 71.
    Warner M, Eskenazi B, Mocarelli P, Gerthoux PM, Samuels S, Needham L, et al. Serum dioxin concentrations and breast cancer risk in the Seveso Women’s Health Study. Environ Heal Perspect. 2002;110(7):625–8.Google Scholar
  72. 72.
    Boffetta P, Mundt KA, Adami HO, Cole P, Mandel JS. TCDD and cancer: a critical review of epidemiologic studies. Crit Rev Toxicol. 2011;41(7):622–36. doi:10.3109/10408444.2011.560141.PubMedGoogle Scholar
  73. 73.
    Manuwald U, Velasco Garrido M, Berger J, Manz A, Baur X. Mortality study of chemical workers exposed to dioxins: follow-up 23 years after chemical plant closure. Occup Environ Med. 2012;69(9):636–42. doi:10.1136/oemed-2012-100682.PubMedGoogle Scholar
  74. 74.
    Van den Berg M, Birnbaum LS, Denison M, De Vito M, Farland W, Feeley M, et al. The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds. Toxicol Sci. 2006;93(2):223–41. doi:10.1093/toxsci/kfl055.PubMedGoogle Scholar
  75. 75.
    Muto T, Wakui S, Imano N, Nakaaki K, Takahashi H, Hano H, et al. Mammary gland differentiation in female rats after prenatal exposure to 3,3′,4,4′,5-pentachlorobiphenyl. Toxicology. 2002;177(2–3):197–205.PubMedGoogle Scholar
  76. 76.
    Oenga GN, Spink DC, Carpenter DO. TCDD and PCBs inhibit breast cancer cell proliferation in vitro. Toxicol In Vitro. 2004;18(6):811–9. doi:10.1016/j.tiv.2004.04.004.PubMedGoogle Scholar
  77. 77.
    Brody JG, Moysich KB, Humblet O, Attfield KR, Beehler GP, Rudel RA. Environmental pollutants and breast cancer: epidemiologic studies. Cancer. 2007;109(12 Suppl):2667–711. doi:10.1002/cncr.22655.PubMedGoogle Scholar
  78. 78.
    LeBlanc GA. Endocrine system. In: Hodgson E, editor. A textbook of modern toxicology. 3rd ed. Hoboken: John Wiley & Sons, Inc; 2004. p. 299–315.Google Scholar
  79. 79.
    Registry AfTSaD, Toxicological profile for DDT, DDE, and DDD, http://www.atsdr.cdc.gov/toxprofiles/tp35.pdf.
  80. 80.
    Johnson NA, Ho A, Cline JM, Hughes CL, Foster WG, Davis VL. Accelerated mammary tumor onset in a HER2/Neu mouse model exposed to DDT metabolites locally delivered to the mammary gland. Environ Heal Perspect. 2012;120(8):1170–6. doi:10.1289/ehp.1104327.Google Scholar
  81. 81.
    Robison AK, Sirbasku DA, Stancel GM. DDT supports the growth of an estrogen-responsive tumor. Toxicol Lett. 1985;27(1–3):109–13.PubMedGoogle Scholar
  82. 82.
    Cohn BA, Wolff MS, Cirillo PM, Sholtz RI. DDT and breast cancer in young women: new data on the significance of age at exposure. Environ Health Perspect. 2007;115(10):1406–14. doi:10.1289/ehp.10260.PubMedGoogle Scholar
  83. 83.
    Agency for Toxic Substances and Disease Registry, Toxicological Profile for Atrazine, http://www.atsdr.cdc.gov/ToxProfiles/tp153.pdf.
  84. 84.
    Rayner JL, Fenton SE. In: Russo J, editor. Atrazine: an environmental endocrine disruptor that alters mammary gland development and tumor susceptibility environment and breast cancer. New York: Springer; 2011. p. 167–83.Google Scholar
  85. 85.
    US Environmental Protection Agency. Atrazine: hazard and dose–response assessment and characterization federal insecticide F, and Rodenticide Act Science Advisory Report, http://www.epa.gov/scipoly/sap/meetings/2000/june27/finalatrazine.pdf.
  86. 86.
    Foradori CD, Hinds LR, Hanneman WH, Handa RJ. Effects of atrazine and its withdrawal on gonadotropin-releasing hormone neuroendocrine function in the adult female Wistar rat. Biol Reprod. 2009;81(6):1099–105. doi:10.1095/biolreprod.109.077453.PubMedGoogle Scholar
  87. 87.
    Stoker TE, Laws SC, Guidici DL, Cooper RL. The effect of atrazine on puberty in male wistar rats: an evaluation in the protocol for the assessment of pubertal development and thyroid function. Toxicol Sci. 2000;58(1):50–9.PubMedGoogle Scholar
  88. 88.
    Stanko JP, Enoch RR, Rayner JL, Davis CC, Wolf DC, Malarkey DE, et al. Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats. Reprod Toxicol. 2010;30(4):540–9. doi:10.1016/j.reprotox.2010.07.006.PubMedGoogle Scholar
  89. 89.
    Enoch RR, Stanko JP, Greiner SN, Youngblood GL, Rayner JL, Fenton SE. Mammary gland development as a sensitive end point after acute prenatal exposure to an atrazine metabolite mixture in female Long-Evans rats. Environ Heal Perspect. 2007;115(4):541–7. doi:10.1289/ehp.9612.Google Scholar
  90. 90.
    Gammon DW, Aldous CN, Carr Jr WC, Sanborn JR, Pfeifer KF. A risk assessment of atrazine use in California: human health and ecological aspects. Pest Manag Sci. 2005;61(4):331–55. doi:10.1002/ps.1000.PubMedGoogle Scholar
  91. 91.
    Stevens JT, Breckenridge CB, Wetzel L. A risk characterization for atrazine: oncogenicity profile. J Toxicol Environ Health A. 1999;56(2):69–109.PubMedGoogle Scholar
  92. 92.
    Eldridge JC, Wetzel LT, Stevens JT, Simpkins JW. The mammary tumor response in triazine-treated female rats: a threshold-mediated interaction with strain and species-specific reproductive senescence. Steroids. 1999;64(9):672–8.PubMedGoogle Scholar
  93. 93.
    Fukamachi K, Han BS, Kim CK, Takasuka N, Matsuoka Y, Matsuda E, et al. Possible enhancing effects of atrazine and nonylphenol on 7,12-dimethylbenz[a]anthracene-induced mammary tumor development in human c-Ha-ras proto-oncogene transgenic rats. Cancer Sci. 2004;95(5):404–10.PubMedGoogle Scholar
  94. 94.
    US Environmental Protection Agency, RED Facts: Vinclozolin http://www.epa.gov/oppsrrd1/REDs/factsheets/2740fact.pdf.
  95. 95.
    Wickerham EL, Lozoff B, Shao J, Kaciroti N, Xia Y, Meeker JD. Reduced birth weight in relation to pesticide mixtures detected in cord blood of full-term infants. Environ Int. 2012;47:80–5. doi:10.1016/j.envint.2012.06.007.PubMedGoogle Scholar
  96. 96.
    Molina-Molina JM, Hillenweck A, Jouanin I, Zalko D, Cravedi JP, Fernandez MF, et al. Steroid receptor profiling of vinclozolin and its primary metabolites. Toxicol Appl Pharmacol. 2006;216(1):44–54. doi:10.1016/j.taap.2006.04.005.PubMedGoogle Scholar
  97. 97.
    Gray Jr LE, Ostby JS, Kelce WR. Developmental effects of an environmental antiandrogen: the fungicide vinclozolin alters sex differentiation of the male rat. Toxicol Appl Pharmacol. 1994;129(1):46–52. doi:10.1006/taap.1994.1227.PubMedGoogle Scholar
  98. 98.
    Kelce WR, Monosson E, Gamcsik MP, Laws SC, Gray Jr LE. Environmental hormone disruptors: evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. Toxicol Appl Pharmacol. 1994;126(2):276–85. doi:10.1006/taap.1994.1117.PubMedGoogle Scholar
  99. 99.
    Anway MD, Leathers C, Skinner MK. Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology. 2006;147(12):5515–23.PubMedGoogle Scholar
  100. 100.
    El Sheikh Saad H, Meduri G, Phrakonkham P, Berges R, Vacher S, Djallali M, et al. Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin. Reprod Toxicol. 2011;32(1):15–25. doi:10.1016/j.reprotox.2011.03.001.PubMedGoogle Scholar
  101. 101.
    Ozen S, Darcan S, Bayindir P, Karasulu E, Simsek DG, Gurler T. Effects of pesticides used in agriculture on the development of precocious puberty. Environ Monit Assess. 2012;184(7):4223–32. doi:10.1007/s10661-011-2257-6.PubMedGoogle Scholar
  102. 102.
    Kamrin MA. Phthalate risks, phthalate regulation, and public health: a review. J Toxicol Environ Health Part B, Crit Rev. 2009;12(2):157–74. doi:10.1080/10937400902729226.Google Scholar
  103. 103.
    Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Heal Perspect. 2005;113(8):1056–61.Google Scholar
  104. 104.
    Rider CV, Wilson VS, Howdeshell KL, Hotchkiss AK, Furr JR, Lambright CR, et al. Cumulative effects of in utero administration of mixtures of “antiandrogens” on male rat reproductive development. Toxicol Pathol. 2009;37(1):100–13. doi:10.1177/0192623308329478.PubMedGoogle Scholar
  105. 105.
    Mylchreest E, Cattley RC, Foster PM. Male reproductive tract malformations in rats following gestational and lactational exposure to Di(n-butyl) phthalate: an antiandrogenic mechanism? Toxicol Sci. 1998;43(1):47–60. doi:10.1006/toxs.1998.2436.PubMedGoogle Scholar
  106. 106.
    Gray Jr LE, Ostby J, Furr J, Price M, Veeramachaneni DN, Parks L. Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol Sci. 2000;58(2):350–65.PubMedGoogle Scholar
  107. 107.
    Agas D, Sabbieti MG, Capacchietti M, Materazzi S, Menghi G, Materazzi G, et al. Benzyl butyl phthalate influences actin distribution and cell proliferation in rat Py1a osteoblasts. J Cell Biochem. 2007;101(3):543–51. doi:10.1002/jcb.21212.PubMedGoogle Scholar
  108. 108.
    Dobrzynska MM, Tyrkiel EJ, Pachocki KA. Developmental toxicity in mice following paternal exposure to Di-N-butyl-phthalate (DBP). Biomed Environ Sci. 2011;24(5):569–78. doi:10.3967/0895-3988.2011.05.017.PubMedGoogle Scholar
  109. 109.
    Crinnion WJ. Toxic effects of the easily avoidable phthalates and parabens. Alternative Med Rev: J Clin Ther. 2010;15(3):190–6.Google Scholar
  110. 110.
    Moral R, Wang R, Russo IH, Mailo DA, Lamartiniere CA, Russo J. The plasticizer butyl benzyl phthalate induces genomic changes in rat mammary gland after neonatal/prepubertal exposure. BMC Genom. 2007;8:453. doi:10.1186/1471-2164-8-453.Google Scholar
  111. 111.
    Moral R, Santucci-Pereira J, Wang R, Russo IH, Lamartiniere CA, Russo J. In utero exposure to butyl benzyl phthalate induces modifications in the morphology and the gene expression profile of the mammary gland: an experimental study in rats. Environ Health. 2011;10(1):5. doi:10.1186/1476-069X-10-5.PubMedGoogle Scholar
  112. 112.
    Dewitt JC, Copeland CB, Strynar MJ, Luebke RW. Perfluorooctanoic acid-induced immunomodulation in adult C57BL/6J or C57BL/6N female mice. Environ Heal Perspect. 2008;116(5):644–50. doi:10.1289/ehp.10896.Google Scholar
  113. 113.
    National Toxicology Program, NTP Toxicology and Carcinogenesis Studies of Butyl Benzyl Phthalate (CAS No. 85-68-7) in F344/N Rats (Feed Studies).Google Scholar
  114. 114.
    Lopez-Carrillo L, Hernandez-Ramirez RU, Calafat AM, Torres-Sanchez L, Galvan-Portillo M, Needham LL, et al. Exposure to phthalates and breast cancer risk in northern Mexico. Environ Health Perspect. 2010;118(4):539–44. doi:10.1289/ehp.0901091.PubMedGoogle Scholar
  115. 115.
    Kang SC, Lee BM. DNA methylation of estrogen receptor alpha gene by phthalates. J Toxi Environ Health A. 2005;68(23–24):1995–2003. doi:10.1080/15287390491008913.Google Scholar
  116. 116.
    Kim IY, Han SY, Moon A. Phthalates inhibit tamoxifen-induced apoptosis in MCF-7 human breast cancer cells. J Toxic Environ Health A. 2004;67(23–24):2025–35. doi:10.1080/15287390490514750.Google Scholar
  117. 117.
    Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Tully JS, Needham LL. Serum concentrations of 11 polyfluoroalkyl compounds in the US population: data from the National Health and Nutrition Examination Survey (NHANES) 1999–2000. Environ Sci Technol. 2007;41:2237–42.PubMedGoogle Scholar
  118. 118.
    Calafat AM, Wong LY, Kuklenyik Z, Reidy JA, Needham LL. Polyfluoroalkyl chemicals in the U.S. population: data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and comparisons with NHANES 1999–2000. Environ Health Perspect. 2007;115(11):1596–602.PubMedGoogle Scholar
  119. 119.
    Olsen GW, Burris JM, Ehresman DJ, Froehlich JW, Seacat AM, Butenhoff JL, et al. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect. 2007;115(9):1298–305.PubMedGoogle Scholar
  120. 120.
    Post GB, Cohn PD, Cooper KR. Perfluorooctanoic acid (PFOA), an emerging drinking water contaminant: a critical review of recent literature. Environ Res. 2012;116:93–117. doi:10.1016/j.envres.2012.03.007.PubMedGoogle Scholar
  121. 121.
    Henry ND, Fair PA. Comparison of in vitro cytotoxicity, estrogenicity and anti-estrogenicity of triclosan, perfluorooctane sulfonate and perfluorooctanoic acid. J Appl Toxicol. 2011. doi:10.1002/jat.1736.
  122. 122.
    Lau C, Thibodeaux JR, Hanson RG, Narotsky MG, Rogers JM, Lindstrom AB, et al. Effects of perfluorooctanoic acid exposure during pregnancy in the mouse. Toxicol Sci. 2006;90(2):510–8. doi:10.1093/toxsci/kfj105.PubMedGoogle Scholar
  123. 123.
    Yang C, Tan YS, Harkema JR, Haslam SZ. Differential effect of peripubertal exposure to perfluorooctanoic acid on mammary gland development in C57Bl/6 and Balb/c mouse strains. Reprod Toxicol. 2009;27(3–4):299–306. doi:10.1016/j.reprotox.2008.10.003.PubMedGoogle Scholar
  124. 124.
    Macon MB, Villanueva LR, Tatum-Gibbs K, Zehr RD, Strynar M, Stanko JP, et al. Prenatal perfluorooctanoic acid exposure in CD-1 mice: low dose developmental effects and internal dosimetry. Toxicol Sci. 2011;122(1):134–45.PubMedGoogle Scholar
  125. 125.
    Dixon D, Reed CE, Moore AB, Gibbs-Flournoy EA, Hines EP, Wallace EA, et al. Histopathologic changes in the uterus, cervix and vagina of immature CD-1 mice exposed to low doses of perfluorooctanoic acid (PFOA) in a uterotrophic assay. Reprod Toxicol. 2012;33(4):506–12.PubMedGoogle Scholar
  126. 126.
    Biegel LB, Liu RC, Hurtt ME, Cook JC. Effects of ammonium perfluorooctanoate on Leydig cell function: in vitro, in vivo, and ex vivo studies. Toxicol Appl Pharmacol. 1995;134(1):18–25. doi:10.1006/taap.1995.1164.PubMedGoogle Scholar
  127. 127.
    Sibinski L. Two-year oral (diet) toxicity/oncogenicity study of fluorochemical FC-143 in rats.: Riker Laboratories Inc/3m Company1987.Google Scholar
  128. 128.
    Lou I, Wambaugh JF, Lau C, Hanson RG, Lindstrom AB, Strynar MJ, et al. Modeling single and repeated dose pharmacokinetics of PFOA in mice. Toxicol Sci. 2009;107(2):331–41. doi:10.1093/toxsci/kfn234.PubMedGoogle Scholar
  129. 129.
    Lopez-Espinosa M, Fletcher T, Armstrong B, Genser B, Dhatariya K, Mondal D, et al. Association of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) with age of puberty among children living near a chemical plant. Environ Sci Technol. 2011. doi:10.1021/es1038694.
  130. 130.
    Knox SS, Jackson T, Javins B, Frisbee SJ, Shankar A, Ducatman AM. Implications of early menopause in women exposed to perfluorocarbons. J Clin Endocrinol Metab. 2011;96(6):1747–53. doi:10.1210/jc.2010-2401.PubMedGoogle Scholar
  131. 131.
    Innes KE, Byers TE. Preeclampsia and breast cancer risk. Epidemiology. 1999;10(6):722–32.PubMedGoogle Scholar
  132. 132.
    Bonefeld-Jorgensen EC, Long M, Bossi R, Ayotte P, Asmund G, Kruger T, et al. Perfluorinated compounds are related to breast cancer risk in Greenlandic Inuit: a case control study. Environ Health. 2011;10:88. doi:10.1186/1476-069X-10-88.PubMedGoogle Scholar
  133. 133.
    White SS, Stanko JP, Kato K, Calafat AM, Hines EP, Fenton SE. Gestational and chronic low-dose PFOA exposures and mammary gland growth and differentiation in three generations of CD-1 mice. Environ Heal Perspect. 2011;119(8):1070–6. doi:10.1289/ehp.1002741.Google Scholar
  134. 134.
    Frisbee SJ, Brooks ABJ, Maher A, Flensborg P, Arnold S, Fletcher T, et al. The C8 health project: design, methods, and participants. Environ Heal Perspect. 2009;117:1873–82.Google Scholar
  135. 135.
    Zhao Y, Tan YS, Strynar MJ, Perez G, Haslam SZ, Yang C. Perfluorooctanoic acid effects on ovaries mediate its inhibition of peripubertal mammary gland development in Balb/c and C57Bl/6 mice. Reprod Toxicol. 2012;33(4):563–76. doi:10.1016/j.reprotox.2012.02.004.PubMedGoogle Scholar
  136. 136.
    Zhao Y, Tan YS, Haslam SZ, Yang C. Perfluorooctanoic acid effects on steroid hormone and growth factor levels mediate stimulation of peripubertal mammary gland development in C57Bl/6 mice. Toxicol Sci. 2010;115(1):214–24. doi:10.1093/toxsci/kfq030.PubMedGoogle Scholar
  137. 137.
    Zhao G, Wang J, Wang X, Chen S, Zhao Y, Gu F, et al. Mutegenicity of PFOA in mammalian cells: role of mitochondtia-dependent reactive oxygem species. Environ Sci Technol. 2011;45:1638–44. doi:10.1021/es1026129.Google Scholar
  138. 138.
    Lipworth L, Hsieh CC, Wide L, Ekbom A, Yu SZ, Yu GP, et al. Maternal pregnancy hormone levels in an area with a high incidence (Boston, USA) and in an area with a low incidence (Shanghai, China) of breast cancer. Br J Cancer. 1999;79(1):7–12. doi:10.1038/sj.bjc.6690003.PubMedGoogle Scholar
  139. 139.
    Bray F, McCarron P, Parkin DM. The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res. 2004;6(6):229–39. doi:10.1186/bcr932.PubMedGoogle Scholar
  140. 140.
    Jefferson WN, Padilla-Banks E, Newbold RR. Disruption of the female reproductive system by the phytoestrogen genistein. Reprod Toxicol. 2007;23(3):308–16. doi:10.1016/j.reprotox.2006.11.012.PubMedGoogle Scholar
  141. 141.
    Trock BJ, Hilakivi-Clarke L, Clarke R. Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst. 2006;98(7):459–71. doi:10.1093/jnci/djj102.PubMedGoogle Scholar
  142. 142.
    Wu AH, Wan P, Hankin J, Tseng CC, Yu MC, Pike MC. Adolescent and adult soy intake and risk of breast cancer in Asian-Americans. Carcinogenesis. 2002;23(9):1491–6.PubMedGoogle Scholar
  143. 143.
    Wu AH, Yu MC, Tseng CC, Pike MC. Epidemiology of soy exposures and breast cancer risk. Br J Cancer. 2008;98(1):9–14. doi:10.1038/sj.bjc.6604145.PubMedGoogle Scholar
  144. 144.
    Su Y, Eason RR, Geng Y, Till SR, Badger TM, Simmen RC. In utero exposure to maternal diets containing soy protein isolate, but not genistein alone, protects young adult rat offspring from NMU-induced mammary tumorigenesis. Carcinogenesis. 2007;28(5):1046–51. doi:10.1093/carcin/bgl240.PubMedGoogle Scholar
  145. 145.
    Hakkak R, Korourian S, Shelnutt SR, Lensing S, Ronis MJ, Badger TM. Diets containing whey proteins or soy protein isolate protect against 7,12-dimethylbenz(a)anthracene-induced mammary tumors in female rats. Cancer Epidemiol Biomarkers Prev. 2000;9(1):113–7.PubMedGoogle Scholar
  146. 146.
    Pei RJ, Sato M, Yuri T, Danbara N, Nikaido Y, Tsubura A. Effect of prenatal and prepubertal genistein exposure on N-methyl-N-nitrosourea-induced mammary tumorigenesis in female Sprague–Dawley rats. In Vivo. 2003;17(4):349–57.PubMedGoogle Scholar
  147. 147.
    Whitsett Jr TG, Lamartiniere CA. Genistein and resveratrol: mammary cancer chemoprevention and mechanisms of action in the rat. Expert Rev Anticancer Ther. 2006;6(12):1699–706. doi:10.1586/14737140.6.12.1699.PubMedGoogle Scholar
  148. 148.
    Fritz WA, Coward L, Wang J, Lamartiniere CA. Dietary genistein: perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat. Carcinogenesis. 1998;19(12):2151–8.PubMedGoogle Scholar
  149. 149.
    Lamartiniere CA. Timing of exposure and mammary cancer risk. J Mammary Gland Biol Neoplasia. 2002;7(1):67–76.PubMedGoogle Scholar
  150. 150.
    National Toxicology Program, Multigenerational reproductive study of genistein (Cas No. 446-72-0) in Sprague–Dawley rats (feed study), 2008/08/08, http://www.ncbi.nlm.nih.gov/pubmed/18685713.
  151. 151.
    Molzberger AF, Vollmer G, Hertrampf T, Moller FJ, Kulling S, Diel P. In utero and postnatal exposure to isoflavones results in a reduced responsivity of the mammary gland towards estradiol. Mol Nutr food Res. 2012;56(3):399–409. doi:10.1002/mnfr.201100371.PubMedGoogle Scholar
  152. 152.
    Latendresse JR, Bucci TJ, Olson G, Mellick P, Weis CC, Thorn B, et al. Genistein and ethinyl estradiol dietary exposure in multigenerational and chronic studies induce similar proliferative lesions in mammary gland of male Sprague–Dawley rats. Reprod Toxicol. 2009;28(3):342–53. doi:10.1016/j.reprotox.2009.04.006.PubMedGoogle Scholar
  153. 153.
    Juan ME, Vinardell MP, Planas JM. The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful. J Nutr. 2002;132(2):257–60.PubMedGoogle Scholar
  154. 154.
    Levi F, Pasche C, Lucchini F, Ghidoni R, Ferraroni M, La Vecchia C. Resveratrol and breast cancer risk. Eur J Canc Prev. 2005;14(2):139–42.Google Scholar
  155. 155.
    Ortega I, Wong DH, Villanueva JA, Cress AB, Sokalska A, Stanley SD, et al. Effects of resveratrol on growth and function of rat ovarian granulosa cells. Fertil Steril. 2012. doi:10.1016/j.fertnstert.2012.08.004.
  156. 156.
    Henry LA, Witt DM. Effects of neonatal resveratrol exposure on adult male and female reproductive physiology and behavior. Dev Neurosci. 2006;28(3):186–95. doi:10.1159/000091916.PubMedGoogle Scholar
  157. 157.
    Nikaido Y, Yoshizawa K, Danbara N, Tsujita-Kyutoku M, Yuri T, Uehara N, et al. Effects of maternal xenoestrogen exposure on development of the reproductive tract and mammary gland in female CD-1 mouse offspring. Reprod Toxicol. 2004;18(6):803–11. doi:10.1016/j.reprotox.2004.05.002.PubMedGoogle Scholar
  158. 158.
    Provinciali M, Re F, Donnini A, Orlando F, Bartozzi B, Di Stasio G, et al. Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int J Cancer. 2005;115(1):36–45. doi:10.1002/ijc.20874.PubMedGoogle Scholar
  159. 159.
    Bhat KP, Lantvit D, Christov K, Mehta RG, Moon RC, Pezzuto JM. Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models. Cancer Res. 2001;61(20):7456–63.PubMedGoogle Scholar
  160. 160.
    Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275(5297):218–20.PubMedGoogle Scholar
  161. 161.
    Massart F, Saggese G. Oestrogenic mycotoxin exposures and precocious pubertal development. Int J Androl. 2010;33(2):369–76. doi:10.1111/j.1365-2605.2009.01009.x.PubMedGoogle Scholar
  162. 162.
    Kuiper-Goodman T, Scott PM, Watanabe H. Risk assessment of the mycotoxin zearalenone. Regul Toxicol Pharmacol: RTP. 1987;7(3):253–306.PubMedGoogle Scholar
  163. 163.
    Hilakivi-Clarke L, Onojafe I, Raygada M, Cho E, Skaar T, Russo I, et al. Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis. Br J Cancer. 1999;80(11):1682–8. doi:10.1038/sj.bjc.6690584.PubMedGoogle Scholar
  164. 164.
    Hilakivi-Clarke L, Cho E, Onojafe I, Raygada M, Clarke R. Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring. Oncol Rep. 1999;6(5):1089–95.PubMedGoogle Scholar
  165. 165.
    Yuri T, Tsukamoto R, Miki K, Uehara N, Matsuoka Y, Tsubura A. Biphasic effects of zeranol on the growth of estrogen receptor-positive human breast carcinoma cells. Oncol Rep. 2006;16(6):1307–12.PubMedGoogle Scholar
  166. 166.
    Saenz de Rodriguez CA, Bongiovanni AM, Conde de Borrego L. An epidemic of precocious development in Puerto Rican children. J Pediatr. 1985;107(3):393–6.PubMedGoogle Scholar
  167. 167.
    Fara GM, Del Corvo G, Bernuzzi S, Bigatello A, Di Pietro C, Scaglioni S, et al. Epidemic of breast enlargement in an Italian school. Lancet. 1979;2(8137):295–7.PubMedGoogle Scholar
  168. 168.
    Bandera EV, Chandran U, Buckley B, Lin Y, Isukapalli S, Marshall I, et al. Urinary mycoestrogens, body size and breast development in New Jersey girls. Sci Total Environ. 2011;409(24):5221–7. doi:10.1016/j.scitotenv.2011.09.029.PubMedGoogle Scholar

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© Springer Science+Business Media New York (outside the USA) 2013

Authors and Affiliations

  1. 1.Curriculum in ToxicologyUniversity of North CarolinaChapel HillUSA
  2. 2.NTP Laboratories, Division of the National Toxicology Program, NIEHS, NIHResearch Triangle ParkUSA

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