Endocrine Disruption Milestones
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This site provides information about EPA's approach toward and progress on screening chemicals for endocrine effects. If you are new to the topic of endocrine disruption you might want to read the EDSP Overview and EDSP Primer for more detailed information on the endocrine system and the EDSP.
An assessment of the state of the science of endocrine disruptors prepared by a group of experts for the United Nations Environment Programme (UNEP) and WHO
The European Commission organised a conference on "Endocrine Disruptors: Current challenges in science and policy" on 11 and 12 June 2012. The presentations and discussions covered the effects of endocrine disruptors on human health and the environment, the risks, the identification of endocrine disruptors and policy objectives (see programme and presentations).
The outcome of the conference will feed into the review of the European Commission's current strategy on endocrine disruptors. It will also provide input to the Commission's upcoming proposal for criteria for the identification of substances with endocrine disrupting properties.
Results from numerous research projects are increasing our knowledge and understanding of the functioning of the endocrine system and its susceptibility and sensitivity to exogenous substances. While it is apparent that many substances may cause changes in the body's hormonal signaling mechanism it is considerably more challenging to identify when such changes will result in adverse effects on health.
In recognition of the need to address the problem of endocrine disrupters, many pieces of EU chemicals' legislation contain specific provisions on this issue. Currently the main focus, both within the EU and internationally, is to agree on approaches for the identification and assessment of endocrine disrupters.
This is our report on the Endocrine Disruptor Screening Program based on a review conducted by the Office of Inspector General (OIG) of the U.S. Environmental Protection Agency (EPA).This report contains findings that describe the problems the OIG has identified and corrective actions the OIG recommends. This report represents the opinion of OIG and does not necessarily represent the final EPA position. Final determinations on matters in this report will be made by EPA managers in accordance with established audit resolution procedures.
In this review, the authors trace the path of knowledge regarding the effects of exogenous agents on the endocrine system, the events which gave rise to the explosion of interest in this topic in the mid-1990’s, and how it led to a fundamentally different paradigm in toxicity testing as well as a great deal of basic research on mechanisms of endocrine-mediated toxicity. We first cover the history of testing for endocrine-mediated toxicity, followed by coverage of key historical events in basic science, and then bring the two together to discuss implications of the science on testing both now and for the future.
The NIEHS supports studies to determine whether exposure to endocrine disruptors may result in human health effects including lowered fertility and an increased incidence of endometriosis and some cancers. Research shows that endocrine disruptors may pose the greatest risk during prenatal and early postnatal development when organ and neural systems are forming.
Draft List of Initial Pesticide Active
Ingredients and Pesticide Inerts to be
Considered for Screening under the
Federal Food, Drug, and Cosmetic Act
This notice describes the approach EPA plans to use for selecting the first group of chemicals to be screened in the Agency’s Endocrine Disruptor Screening Program (EDSP).
The Endocrine Disruptor Methods Validation Advisory Committee (EDMVAC) was established in accordance with the Federal Advisory Committee Act (5 U.S.C. App. 2 Section 9c)) and was formed to replace EDMVS. The EDMVAC will continue to function like EDMVS by providing advice and recommendations to EPA on scientific and technical aspects of the Tier I screens and Tier II assays being considered for the Endocrine Disruptor Screening Program. The committee will evaluate relevant scientific issues, protocols, data, and interpretations of the data for the assays during the validation process. EDMVAC will also provide advice on the composition of the Tier I screening battery.
Researchers find for the first time that human sperm quality varies regionally with lower quality in Midwestern rural farming areas and higher quality in urban areas suggesting environmental factors such as pesticides might affect sperm health. Swan, SH et al. Geographic differences in semen quality of fertile US males. Environmental Health Perspectives, 111(4):414-420 (2003). doi:10.1289/ehp.5927 available via http://dx.doi.org/ (Online 11 November 2002).
The US Environmental Protection Agency (EPA) will ban lumber treated with the wood preservative chromated copper arsenate (CCA) for home use in the US by January 1, 2004.
Frogs exposed during development to low levels of atrazine, the most widely used pesticide in the US, are feminized and hermaphrodites, according to published research. Hayes, TB, et al. Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses. Proceedings of the National Academy of Sciences, 99(8, April 16): 5476-5480 (2002). Hayes, TB, K Haston, M Tsui, A Hoang, C Haeffele, and A Vonk. Feminization of male frogs in the wild. Nature, 419, 895-896 (2002).
The synthetic hormone diethylstilbestrol (DES) is shown for the first time to affect a third generation in humans. Klip, H. et al. Hypospadias in sons of women exposed to diethylstilbestrol in utero: A cohort study. The Lancet, 359(Mar 30):1102-1107 (2002).
A US Geologic Survey (USGS) study found low concentrations of human and animal drugs, natural and synthetic hormones, detergents, plasticizers, insecticides, and fire retardants in most of the 139 stream sites sampled in 30 states during 1999-2000. Kolpin, DW, et al. Pharmaceuticals, hormones, and other organic wastewater contaminants in US streams, 1999-2000: A national reconnaissance. Environmental Science & Technology, 36(6, Mar 15):1202-1211 (2002). Velagaleti, R, et al. Impact of current good manufacturing practices and emission regulations and guidances on the discharge of pharmaceutical chemicals into the environment from manufacturing, use, and disposal. Environmental Health Perspectives, 110(3):213-22 (2002).
The Hormone Disruption Research Act of 2002, a bill to authorize the National Institute of Environmental Health Sciences (NIEHS) to conduct and coordinate a research program on hormone disrupting chemicals, was introduced to the US House of Representatives on May 9, 2002, by Rep. Louise Slaughter (New York, Democrat).
A global assessment of endocrine disrupter research finds that some wildlife species suffer adverse health effects from exposure to endocrine disrupting chemicals (EDCs) warranting concern for human health but strong evidence linking exposure to health problems is missing due to incomplete and insufficient data, understanding, and knowledge. The report recommends international research programs to prioritize and gather information about this global priority issue.
Global Assessment of the State-of-the-Science of Endocrine Disruptors. Report. International Programme on Chemical Safety (IPCS), World Health Organization. 180 pp. 12 August 2002.
The National Toxicology Program's (NTP) lists steroidal estrogens as a known cause of cancer in humans.
Female Chinook salmon in wild populations are found to be genetically male and researchers speculate hormone-altering chemicals from land runoff up river or water temperature changes from hydroelectric dams are the two most likely suspects. Nagler, JJ, J Bouma, GH Thorgaard, and DD Dauble. High incidence of a male-specific genetic marker in phenotypic female chinook salmon from the Columbia River. Environmental Health Perspectives, 109(1):67-69 (2001).
Center for Disease Control and Prevention (CDC) published the first National Exposure Report Card. The agency measured a variety of toxic substances in people's blood and urine to determine the kinds and amounts of chemicals found in the US population in an effort to better understand chemical risks.
More research finds that penta bromo diphenyl ether or PBDE is widely contaminating wildlife, the environment, and people. Hale, RC et al. Polybrominated diphenyl ether flame retardants in Virginia freshwater fishes (USA). Environmental Science and Technology, 35(23, December 1):4585-4591 (2001).
Global ban of 12 persistent organic pollutants (POPs) is solidified in a global treaty during a summit in Johannesburg, South Africa, in early December.Scientists begin monitoring and assessing the health risk of pharmaceutical and personal care products from treated and untreated sewage that end up in surface and groundwater used for drinking water. Potera, C. Drugged drinking water. Environmental Health Perspectives, 108(10):446. (2000).
Book reviewing how endocrine disrupting chemicals became a social and political concern is published. Krimsky, S. Hormone Chaos: The Scientific and Social Origins of the Environmental Endocrine Hypothesis. Baltimore:John Hopkins University Press. (2000). 256 pp.
A National Research Council report (released August 3) published as a book finds that even though there is evidence of adverse effects from exposure to high levels of hormonally active substances, more research is needed to determine the compounds' overall health and ecological effects as well as their impact at low concentrations. National Research Council. Hormonally active agents in the environment. Washington:National Academy Press. (1999). 560 pp
National Public Television's FRONTLINE airs the hour-long show Fooling with Nature Tuesday, June 2, 1998. Interviews with scientists, politicians, activists and business officials explore concerns that environmental toxins may be altering endocrine systems in animals and humans.
The Endocrine Disruptor Screening Program is convened by the US Environmental Protection Agency to use EDSTAC's final recommendations from September 1998 to develop a screening program with methods and procedures to detect and characterize endocrine activity of pesticides, commercial chemicals, and environmental contaminants and enabling the agency to gather the information necessary to identify endocrine disruptors and take appropriate regulatory action.
Estrogens in the Environment IV: Linking Fundamental Knowledge, Risk Assessment, and Public Policy (July 20 - 23). Conference sponsored by the National Institute of Environmental Health Sciences. Proceedings: Estrogens in the Environment IV: Linking Fundamental Knowledge, Risk Assessment, and Public Policy. Environmental Health Prospectives.
Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) established in the fall to advise the US Environmental Protection Agency on a strategy for screening and testing chemicals and pesticides for their potential to disrupt endocrine functions in humans and wildlife. Health Effects of Contemporary-use Pesticides: The Wildlife/Human Connection (September 27-29, Racine, Wisconsin). Second Wingspread Workshop convened by Theo Colborn and sponsored by the World Wildlife Fund and the Johnson Foundation. Presentations focused on how pesticides affect the endocrine system, the immune system and behavior. Proceedings: Chemically induced alterations in functional development and reproduction of fishes. Rolland, RM., M Gilbertson, and R Peterson, eds. Pensacola, FL: Society of Environmental Toxicology and Chemistry (SETAC). 1997. 220 pp. Thirteen chapters assess the current threat to fish populations from environmental chemicals and present original research/reviews and ecoepidemiological research on the effects of environmental chemicals on freshwater and saltwater fish populations. Food Quality Protection Act (FQPA) of 1996 enacted August 3, 1996.
Our Stolen Future published. Book documents research on endocrine disrupting chemicals. T. Colborn, D. Dumanoski and J.P. Myers. Our Stolen Future. New York: Penguin Books. (1996).
Male Reproductive Health and Environmental Chemicals with Estrogenic Effects published by Ministry of Environment and Energy, Denmark. Report summarizes current scientific evidence on male human and wildlife reproductive disorders and environmental chemicals with estrogenic effects. Toppari, J., J. Larsen, P. Christiansen, et. al. Male Reproductive Health and Environmental Chemicals with Estrogenic Effects. Miljoprojekt, nr. 290. Copenhagen: Ministry of Environment and Energy, Danish Environmental Protection Agency. (1995).
Hormone Related Toxicants in the Environment. (October). 1st meeting of the National Academy of Sciences, National Research Council panel study.
Estrogens in the Environment III: Global Health Implications (January 9 - 11). Conference sponsored by the National Institute of Environmental Health Sciences. Proceedings: Estrogens in the Environment III: Global Health Implications. Environmental Health Prospectives 103(Supplement 7):October. (1995).
Sewage effluent shown to have estrogenic effects on fish (rainbow trout). Jobling, S. and J.P. Sumpter. Detergent components in sewage effluent are weakly oestrogenic to fish: An in vitro study using rainbow trout (Oncorhyncus mykiss) hepatocytes. Aquatic Toxicology, 27:361-372 (1993). Assault on the Male. A BBC documentary discussing the possible link between endocrine-disrupting chemicals and reproductive problems observed in both wildlife and humans worldwide.
Link between environmental estrogens and male reproductive problems hypothesized in scientific papers. Sharpe, R.M. Falling sperm counts in men - Is there an endocrine cause? Journal of Endocrinology 137:357-360 (1993). Sharpe, R.M. and N.F. Shakkebaek. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet 341:1392-95 (1993).
Chemically Induced Alterations in Sexual Development: The Wildlife/Human Connection. (July). Wingspread Workshop convened by Theo Colborn. Presented evidence that compounds may have deleterious effects on sexual development in a variety of wildlife species, including reproductive decline in individuals, especially top predators; low population growth; and offspring born with adult features. Proceedings: Chemically-induced Alterations in Sexual and Functional Development: The Wildlife/Human Connection. Colborn, T. and C.R. Clement, eds. Princeton, NJ: Princeton Scientific Pub. Co. (1992). Some plastic compounds used in a variety of consumer products are shown to be estrogenic in laboratory research. Soto, A.M., T.M. Lin, H. Justicia, J.W. Wray, and C. Sonneschein. p-Nonylphenol: An estrogenic xenobiotic released from "modified" polystyrene. Environmental Health Perspectives, 92:167-173 (1991). Government Regulation of Reproductive Hazards. Report from the 102nd U.S. Congress, Senate Committee on Governmental Affairs. Proceedings: Washington, DC: U.S. Government Publications Office. (1992).
Estrogens in the Environment II: Influences on Development. (April). Conference sponsored by the National Institute of Environmental Health Sciences. Presentations addressed the effects of environmental estrogens on puberty in young children, ubiquitous nature of the contaminants, their potency and their potential impact on public and environmental health. Proceedings: Estrogens in the Environment II: Influences on Development. J.A. McLachlan, ed. New York: Elsevier. (1985).
DES shown to cause developmental abnormalities in female mice. McLachlan, J.A., R.R. Newbold, and B.C. Bullock. Long-term effects on the female mouse genital tract associated with prenatal exposure to diethylstilbestrol. Cancer Research, 40:3988-3999 (1980).
Estrogens in the Environment I. (September). Conference sponsored by the National Institute of Environmental Health Sciences. Inadvertent and advertent hormones were identified and evaluated. Proceedings: Estrogens in the Environment. J.A. McLachlan, ed. New York: Elsevier. (1980).
Use and manufacture of PCBs restricted by the U.S. Environmental Protection Agency.
DES shown to cause developmental abnormalities in male mice. McLachlan, J.A., R. Newbold and B. Bullock. Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol. Science, 190:991-992 (1975).
DES linked to human reproductive problems. Herbst, A.L., D.C. Poskanzer, S.J. Robboy, L. Fiedlander, and R.E. Scully. Prenatal exposure to stilbestrol: A prospective comparison of exposed female offspring with unexposed controls. New England Journal of Medicine. 292:334-339 (1975). Gill, W.B., G.F.B. Schumacher and M. Bibbo. Structural and functional abnormalities in the sex organs of male offspring of mothers treated with diethylstilbestrol (DES). Journal of Reproductive Medicine, 16:147-153 (1976).
DDT use restricted in agriculture by the U.S. Environmental Protection Agency.
U.S. Food and Drug Administration directs doctors not to prescribe DES to pregnant women and bans the drug from animal use.
DES linked to vaginal cancer in daughters whose mothers had taken the drug during the first three months of pregnancy. Herbst, A., H. Ulfelder, and D. Poskanzer. Adenocarcinoma of the vagina: Association of maternal stilbestrol therapy with tumor appearance in young women. New England Journal of Medicine, 284:878-881 (1971).
DDT shown to be estrogenic in mammals and birds. Bitman, J., H.C. Cecil, S.J. Harris, and G.F. Fries. Estrogenic activity of o,p'-DDT in the mammalian uterus and avian oviduct. Science, 162:371-72 (1968).
Study shows that newborn mice receiving estrogen injections developed tissue pathologies (cysts, cancers, lesions). Results indicated that exposure to naturally occurring hormones early in life can produce harmful health effects and pointed to possible early life causes of cancer in adult human populations. Dunn, T. and A. Green. Cysts of the epididymis, cancer of the cervix, granular cell myoblastoma and other lesions after estrogen injection in newborn mice. Journal of the National Cancer Institute, 31:425-38 (1963). Takasugi, N. and H.A. Bern. Tissue changes in mice with persistent vaginal cornification induced by early postnatal treatment with estrogen. J. Natl. Cancer Inst. 33:855-65 (1964). Foresbert, J.G. The development of atypical epithlium in the mouse uterine cervix and vaginal fornix after neonatal estradiol treatment. Br. J. Exp. Pathol. 50:187-95 (1969).
Silent Spring published. Rachel Carson's book describes health problems observed in wildlife (egg shell thinning, deformaties, population declines) and links them to exposure to pesticides and other synthetic chemicals. Carson, R. Silent Spring. Boston: Houghton Mifflin. (1962).
DDT shown to be estrogenic. Burlington, H. and V. Lindeman. Effect of DDT on testes and secondary sex characters of white leghorn cockerels. Proceedings of the Society for Experimental Biology and Medicine, 74:48-51 (1950).
First estrogen bioassay developed. The test detected estrogenic activity in biological extracts and determined relative potencies of compounds and mixed natural materials. Allen, E. and E.A. Doisy. An ovarian hormone: Preliminary report on its localization, extraction and partial purification and action in test animals. Journal of the American Medical Association, 81:819 (1923).