1 BCUK Fact Sheet | Endocrine Disrupting Chemicals The human endocrine system is a collecon of glands which secrete different types of hormones that regulate the body’s growth and metabolism, sexual development, and behaviour (Fig 1). Hormones are released into the bloodstream and transported to ssues and organs. They bind to specific target cells and iniate biological processes that ulmately lead to changes in cell funcon. Oestrogens are responsible for female sexual development and reproducon. Androgens are responsible for the development and maintenance of male sexual characteriscs. Hormones are acve at very low doses and their regulaon is ghtly controlled by the endocrine and central nervous systems. Hormone related diseases that result in hormone imbalance are common and may be caused by over or underproducon of specific hormones, or insensivity of target cells. A healthy endocrine system is essenal to the normal funconing of the human body What are endocrine disrupting chemicals (EDCs)? An Endocrine Disrupng Chemical (EDC) or Endocrine Disruptor (ED) is any chemical that can interfere with normal hormone funcons in humans and/or animals 1 . Although details of how EDCs exert their effects are not fully understood some general mechanisms have been described 2,3 . Some EDCs are “agonists” or “mimics” . These are structurally similar to naturally occurring hormones. They are able to bind to specific hormone receptors, which in turn induce the chemical reacons normally associated with natural hormones. Some are “antagonists”, so prevent hormone-receptor binding thus blocking subsequent acons. Others can alter the concentraon of naturally circulang hormones. There are also those that cause heritable changes through “epigenec” modificaon, which changes gene expression without altering the underlying DNA gene sequence. This mechanism is parcularly relevant in relaon to prenatal and early exposures. Some EDCs are present in our natural environment including phytoestrogens (found in plants), however, most EDCs are synthec compounds 4 . Almost 1000 compounds are known or suspected to be EDCs 5 . Only a small fracon of these has been invesgated in tests capable of idenfying endocrine effects in intact organisms. Breast Cancer UK Ltd, BM Box 7767, London, WC1N 3XX | www.breastcanceruk.org.uk | 0845 680 1322 Charity no: 1138866 | Company Number : 7348408 Registered Address: BCUK Ltd, Solva, Southwick Road, Denmead, Waterlooville, Hants, PO7 6LA What is the Endocrine System? Fig 1: Major Endocrine Glands
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BCUK Fact Sheet | Endocrine Disrupting Chemicals · 1 BCUK Fact Sheet | Endocrine Disrupting Chemicals The human endocrine system is a collection of glands which secrete different
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BCUK Fact Sheet | Endocrine Disrupting Chemicals
The human endocrine system is a collection of
glands which secrete different types of hormones
that regulate the body’s growth and metabolism,
sexual development, and behaviour (Fig 1).
Hormones are released into the bloodstream and
transported to tissues and organs. They bind to
specific target cells and initiate biological
processes that ultimately lead to changes in cell
function. Oestrogens are responsible for female
sexual development and reproduction.
Androgens are responsible for the development
and maintenance of male sexual characteristics.
Hormones are active at very low doses and their
regulation is tightly controlled by the endocrine
and central nervous systems. Hormone related
diseases that result in hormone imbalance are
common and may be caused by over or
underproduction of specific hormones, or
insensitivity of target cells. A healthy endocrine
system is essential to the normal functioning of
the human body
What are endocrine disrupting chemicals (EDCs)?
An Endocrine Disrupting Chemical (EDC) or
Endocrine Disruptor (ED) is any chemical that can
interfere with normal hormone functions in
humans and/or animals1. Although details of how
EDCs exert their effects are not fully understood
some general mechanisms have been described2,3.
Some EDCs are “agonists” or “mimics” . These are
structurally similar to naturally occurring
hormones. They are able to bind to specific
hormone receptors, which in turn induce the
chemical reactions normally associated with
natural hormones. Some are “antagonists”, so
prevent hormone-receptor binding thus blocking
subsequent actions. Others can alter the
concentration of naturally circulating hormones.
There are also those that cause heritable changes
through “epigenetic” modification, which changes
gene expression without altering the underlying
DNA gene sequence. This mechanism is
particularly relevant in relation to prenatal and
early exposures.
Some EDCs are present in our natural
environment including phytoestrogens (found in
plants), however, most EDCs are synthetic
compounds4. Almost 1000 compounds are
known or suspected to be EDCs5. Only a small
fraction of these has been investigated in tests
capable of identifying endocrine effects in intact
organisms.
Breast Cancer UK Ltd, BM Box 7767, London, WC1N 3XX | www.breastcanceruk.org.uk | 0845 680 1322
Breast Cancer UK is calling for: The regulation of chemicals to be strengthened and improved, based on the
precautionary principle, to pro-actively protect public health;
Hazardous chemicals, including EDCs, to be recognised as preventable risk factors for breast cancer in all UK National Cancer Plans;
The extension of EU Article 60 (3) of the REACH Regulation, to ensure EDCs are, by default, classed as Substances of Very High Concern (SVHC), for which no safe thresholds can be determined;
An increase in the proportion of cancer research funding for prevention and the investigation of the environmental and chemical causes of breast cancer.
1.IPCS. (2002). Global assessment of the state-of-the-science of endocrine disruptors. Geneva, Switzerland, World Health Organization, International Programme on Chemical Safety. http://www.who.int/ipcs/publications/en/ch1.pdf?ua=1 2.Diamanti-Kandarakis E, et al., (2009). Endocrine- disrupting chemicals: an Endocrine Society scientific statement. Endocrine Reviews, 30(4): 293–342. http://www.ncbi.nlm.nih.gov/pubmed/19502515 3.Soto AM, et al., (2013). Does cancer start in the womb? altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors. Journal of Mammary Gland Biology Neoplasia 18(2): 199-208. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933259/ 4.UNEP/WHO (2013). State of the science of endocrine disrupting chemicals 2012 http://www.unep.org/hazardoussubstances/Portals/9/EDC/StateOfEDCScience.pdf 5.TEDX. http://endocrinedisruption.org/endocrine-disruption/tedx-list-of-potential-endocrine-disruptors/overview http://endocrinedisruption.org/endocrine-disruption/tedx- 6.UNEP/WHO (2013). Op.cit., 7.UNEP/WHO (2013). Ibid., 8.Calafat AM, et al., (2008). Exposure of the U.S. population to bisphenol A and 4-tertiary-Octylphenol: 2003–2004. Environmental Health Perspectives 116: 39–44.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199288/ 9.Ikezuki Y, et al., (2002). Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Human Reproduction 17: 2839–2841.http://www.ncbi.nlm.nih.gov/pubmed/12407035 10.Vandenberg LN, et al., (2010). Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A. Environmental Health Perspectives 118 (8) 1055-1070. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920080/ 11.Letcher, R.J. et al., (2010). Exposure and effects assessment of persistent organohalogen contaminants in arctic wildlife and fish. Science of the Total Environment 408: 2995–3043 http://www.ncbi.nlm.nih.gov/pubmed/19910021 12.Sonne, C. (2010). Health effects from long-range transported contaminants in Arctic top predators: An integrated review based on studies of polar bears and relevant model species. Environment International 36: 461–491. http://www.ncbi.nlm.nih.gov/pubmed/20398940 13.Gross-Sorokin MY, et al., (2006). Assessment of feminization of male fish in English rivers by the Environment Agency of England and Wales. Environmental Health Perspectives 114 (1):147-51.http://www.unboundmedicine.com/medline/citation/16818261/Assessment_of_feminization_of_male_fish_in_English_rivers_by_the_Environment_Agency_of_England_and_Wales_ 14.Jobling, S, et al., (2009). Statistical Modelling Suggests that Antiandrogens in Effluents from Wastewater Treatment Works Contribute to Widespread Sexual Disruption in Fish Living in English Rivers Environmental Health Perspectives 117 797–802. http://www.ncbi.nlm.nih.gov/pubmed/19479024 15.UNEP/WHO (2013). Op.cit., 16.Sonne, C. (2010). Op.cit., 17.EEA. (2012). The impacts of endocrine disrupters on wild-life, people and their environments—The Weybridge+15 (1996–2011) report. http://www.eea.europa.eu/publications/the-impacts-of-endocrine- disrupters
18.Kloas W, et al., (2009) Endocrine disruption in aquatic vertebrates. Annual N Y Academy Sciences. 1163: 187-200. http://www.ncbi.nlm.nih.gov/pubmed/19456339 19.Schwacke LH, et al., (2011). Anaemia, hypothyroidism and immune suppression associated with polychlorinated biphenyl exposure in bottlenose dolphins (Tursiops truncatus). Proceedings of the Royal Society B: Biological Sciences 279(1726): 48-57 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223648/ 20.Davison NJ, et al., (2011). Infection with Brucella ceti and high levels of polychlorinated biphenyls in bottlenose dolphins (Tursiops truncatus) stranded in south-west England. Veterinary Record 169 (1):14. www.unboundmedicine.com/medline/citation/21676987/Infection_with_Brucella_ceti_and_high_levels_of_polychlorinated_biphenyls_in_bottlenose_dolphins__Tursiops_truncatus__stranded_in_south_west_England 21.Boas M, et al., (2012). Thyroid effects of endocrine disrupting chemicals. Molecular and Cellular Endocrinology 355 (2) 240-248.http://www.ncbi.nlm.nih.gov/pubmed/21939731 22.UNEP/WHO (2013). Op.cit., 23.UNEP/WHO (2013). Ibid., 24.EEA. (2012). Op.cit., 25.Berlaymont Declaration, (2013). http://www.brunel.ac.uk/__data/assets/pdf_file/0005/300200/The_Berlaymont_Declaration_on_Endocrine_Disrupters.pdf accessed sep 28 26.Kortenkamp, A. (2007). ‘Ten Years of Mixing Cocktails: A Review of Combination Effects of Endocrine-Disrupting Chemicals. Environmental Health Perspectives 115(1): 98–105. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174407/. 27.Payne, J., Scholze, M. and Kortenkamp, A. (2001). Mixtures of four organochlorines enhance human breast cancer cell proliferation. Environmental Health Perspectives, 109 (4): 391–397. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240280/. 28.Travis, RC. and Key, TJ. (2003). Oestrogen exposure and breast cancer risk. Breast Cancer Research 5: 239-247. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC314432/ 29.Travis, RC. and Key, TJ. (2003). Ibid., 30.Reed, CE and Fenton, SE (2013). Exposure to diethylstilbestrol during sensitive life stages: a legacy of heritable health effects. Birth Defects Research Part C Embryo Reviews Today 99(2): 134-46. http://www.ncbi.nlm.nih.gov/pubmed/23897597 31.Jenkins S, et al., (2012). Endocrine-active chemicals in mammary cancer causation and prevention. Journal of Steroid Biochemistry and Molecular Biology. 129(3-5): 191-200. http://www.ncbi.nlm.nih.gov/pubmed/21729753 32.Jobling, S, et al., (1995). A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environmental Health Perspectives 103: 582-587. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1519124/ 33.Kang, SC and Lee, BM (2005). DNA methylation of estrogen receptor α gene by phthalates. Journal of Toxicology and Environmental Health, 68:1995-2003. http://www.ncbi.nlm.nih.gov/pubmed/16326419 34.Aksglaede, L., et al., (2006). The sensitivity of the child to sex steroids: possible impact of exogenous estrogens. Human Reproduction Update 12: 341–349. http://www.ncbi.nlm.nih.gov/pubmed/16672247
For further information and more web resources please visit our website www.breastcanceruk.org.uk
Breast Cancer UK Ltd, BM Box 7767, London, WC1N 3XX | www.breastcanceruk.org.uk | 0845 680 1322
35.Dhimolea E, et al. (2014). Prenatal Exposure to BPA Alters the Epigenome of the Rat Mammary Gland and Increases the Propensity to Neoplastic Development. PLoS ONE 9(7): e99800. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0099800 36. Hsieh, T.-H., et al., (2012). Phthalates induce proliferation and invasiveness of estrogen receptor-negative breast cancer through the AhR/HDAC6/c-Myc signaling pathway. FASEB Journal, 26(2): 778–787. http://www.fasebj.org/content/26/2/778.full.pdf 37.Romero-Franco, M, et al., (2010). Personal care product use and urinary levels of phthalate metabolites in Mexican women. Environment International 37(5): 867-71.http://www.ncbi.nlm.nih.gov/pubmed/21429583 38.Borch, J., et al., (2006). Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis. Toxicology 223: 144–155.http://www.ncbi.nlm.nih.gov/pubmed/16690193 39.Fang, H., et al., (2003). Study of 202 Natural, Synthetic, and Environmental Chemicals for Binding to the Androgen Receptor. Chemical Research Toxicology 16(10): 1338–1358.http://www.ncbi.nlm.nih.gov/pubmed/14565775 40. Darbre PD and Harvey PW. (2014). Parabens can enable hallmarks and characteristics of cancer in human breast epithelial cells: a review of the literature with reference to new exposure data and regulatory status. Journal Applied Toxicology 34(9):925-38.http://onlinelibrary.wiley.com/doi/10.1002/jat.3027/abstract 41.Darbre PD. (2006). Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast. Journal of Applied Toxicology. 26(3): 191-7. http://www.ncbi.nlm.nih.gov/pubmed/16489580 42.Kortenkamp A, et al., (2011). State of the art assessment of endocrine disrupters. Final report. European Commission, Directorate-General for the Environment (Project Contract No. 070307/2009/550687/SER/D3). http://ec.europa.eu/environment/chemicals/endocrine/pdf/sota_edc_final_report.pdf 43.Exley C, et al., (2007). Aluminium in human breast tissue. Journal of Inorganic Biochemistry 101(9):1344-6.http://www.ncbi.nlm.nih.gov/pubmed/17629949 44.Report of the Interagency Breast Cancer and Environmental Research Coordinating Committee (IBCERCC) (2013). ‘Breast Cancer and the Environment Prioritising Prevention Prioritising Breast Cancer’. http://www.niehs.nih.gov/about/assets/docs/ibcercc_full_508.pdf. 45.Barouki, R, et al., (2012). Developmental origins of non-communicable disease: Implications for research and public health. http://www.toxicology.org/AI/MEET/cct_pptoxiii/pptoxiii_consensus_paper.pdf 46.EEA. (2012). Op.cit., 47.UNEP/WHO (2013). Op.cit., 48. Knower. KC, et al., (2014). Endocrine disruption of the epigenome: a breast cancer link Endocrine Related Cancer 21(2): T33-55.http://www.ncbi.nlm.nih.gov/pubmed/24532474 49.Darbre, PD and Charles, AK (2010). Environmental Oestrogens and Breast Cancer: Evidence for Combined Involvement of Dietary, Household and Cosmetic Xenoestrogens. Anticancer Research 30: 815-828. http://www.ncbi.nlm.nih.gov/pubmed/20393002 50.Soto AM, et al., (2013). Op. cit., 51. Cohn BA, et al., (2007). DDT and breast cancer in young women: new date on the significance of age at exposure. Environmental Health
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For further information and more web resources please visit our website www.breastcanceruk.org.uk
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